Epidemiological characteristics of respiratory viruses in children during the COVID-19 epidemic in Chengdu, China.

IMPORTANCE: During the coronavirus disease 2019 epidemic, the Chinese government launched and used a series of nonpharmaceutical interventions (NPIs), including banning social gatherings, wearing face masks, home isolation, and maintaining hand hygiene, to control the disease spread. Whether and how NPIs influence other respiratory viruses in children remain unclear. In this article, we analyzed relative data and found that the number of samples and positive proportion of respiratory viruses decreased significantly compared with that before the epidemic. Clinicians and public health policymakers should pay attention to changes in the epidemic trends and types of respiratory viruses and maintain monitoring of respiratory-related viruses to avoid possible abnormal rebounds and epidemic outbreaks of these viruses.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children.

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12-1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P < .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P > .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P > .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Antinuclear Antibodies in Erythema Multiforme: Transient Occurrence During Acute Illness.

BACKGROUND: Children with target lesions are frequently diagnosed with erythema multiforme (EM). EM was not previously thought to be associated with any specific autoimmune serological abnormality. METHODS: We report the case of a 7-year-old girl who developed rashes all over her body with target shaped lesions. Based on clinical appearance and medical history, she was diagnosed with severe erythema multiforme and treated with methylprednisolone. Relevant laboratory tests were performed at admission. RESULTS: At the height of her infection, the antinuclear antibody (ANA) test showed a positive ANA with a titer of 1:100 (speckled pattern) and positive anti-SSA and anti-Ro-52 antibodies. Then she was adjusted for medication. After a week, the infection was relieved, and the re-examination was negative for ANA, anti-SSA, and anti-Ro-52 antibodies. CONCLUSIONS: In previously reported EM cases, ANA is generally not considered to be present. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of EM infection. Its correlation with infection severity warrants further research on the mechanism of autoantibody formation in EM.

Advances in laboratory diagnostic methods for cerebrospinal fluid testing for neurosyphilis.

Neurosyphilis is a chronic infectious disease caused by the invasion of Treponema pallidum into the central nervous system. In recent years, with the increase in the latent syphilis infection rate, the incidence of neurosyphilis has gradually increased, the typical symptoms of neurosyphilis have decreased, atypical manifestations have increased, and the clinical manifestations have become increasingly diverse. Cerebrospinal fluid testing plays an important role in the diagnosis of neurosyphilis. In recent years, there have been many advances in cerebrospinal fluid testing. This review focuses on the current and potential laboratory indicators of neurosyphilis in cerebrospinal fluid, aiming to provide a reference for clinical application and ideas for future experimental research of neurosyphilis.

Analysis of Aeroallergens in Sichuan Province after the COVID-19 Epidemic.

BACKGROUND: Identifying the distribution and pattern of specific aeroallergens in Sichuan, China, after the corona-virus disease (COVID-19) epidemic and to provide a basis for future prevention and clinical treatment. METHODS: Serological tests for 10 types of aeroallergens were performed on 10,036 participants attending the West China Second University Hospital from January 2020 to January 2021. SPSS23.0 was used to statistically analyze their specific immunoglobulin E (sIgE) grades in different genders, various age groups, and different diseases. RESULTS: Of the 10,036 participants, 4,578 (45.62%) were allergic to at least one allergen. House dust had the highest sensitization rate (2,974, 29.63%), followed by Dermatophagoides farina (2,717, 27.07%) and Dermatophagoides pteronyssinus (2,611, 26.02%). Male and female participants had no significant difference in overall sensitization distributions. The prevalence differences between 0 - 3, 4 - 6, 7 - 9, 10 - 12, 13 - 15, and over 16-year-old age groups were statistically significant (p < 0.05), and the highest incidence age for children to be sensitive to aeroallergens was 4 - 6 years, respectively. Sensitization to D. pteronyssinus, D. farina, house dust, dog epithelium, and Alternaria alternata was more common in patients with rhinitis and asthma compared with bronchitis. CONCLUSIONS: Aeroallergens are important causes of respiratory-related allergic diseases, and the characteristics of allergen sensitization discovered in this study could help with inhalant allergy disease prevention, diagnosis, and management in the post-epidemic era.

Missed opportunities for screening congenital syphilis early during pregnancy: A case report and brief literature review.

Congenital syphilis is a significant public health problem. Pregnant women infected with Treponema pallidum present with various clinical manifestations, mainly including skin or visceral manifestations. The extensive clinical manifestations of T. pallidum infection mimic those of many other diseases during pregnancy, which may lead to delayed diagnosis and serious consequences. We report a case of fetal T. pallidum infection and premature delivery in a woman whose syphilis screening was negative at 16 weeks of gestation. Despite presenting to the dermatologist at 24 weeks of gestation with maculopapular rash which is usually associated with secondary syphilis, the diagnosis of syphilis was not considered. This case shows that even if early syphilis screening of pregnant women is negative, they may still get infected with T. pallidum later on in pregnancy. Therefore, in patients presenting with a rash without an obvious cause, T. pallidum infection should be excluded. The health status of patients' spouses should be assessed during pregnancy. Additionally, perinatal health education is necessary for women and their spouses during pregnancy. The abovementioned factors could reduce the probability of T. pallidum infection in pregnant women and their infants.

A Rare Antinuclear Antibody Fluorescence Pattern Induced by Rodenticides: a Case Report.

BACKGROUND: Warfarin and superwarfarins, which belong to anticoagulants, are also widely used as rodenticides worldwide. Cases of accidental ingestion of these kinds of rodenticides often occur, and the patients usually have clinical symptoms of various systemic bleeding which are, in serious cases, life threatening. METHODS: We reported a 12-year-old boy poisoned by superwarfarins. He was initially diagnosed with coagulation disorder induced by rodenticides and was treated with vitamin K. A month after the onset of the disease, the patient was further treated in our hospital. We improved his relevant laboratory tests and found that his antinuclear antibody (ANA) and anti-SSA antibodies were positive. After the patient was cured and discharged, the result of ANA turned negative four months later. RESULTS: The ANA fluorescence pattern of the patient presented a rare cytoplasmic granular type with low titer, which appeared when the patient was poisoned and disappeared after cured. In the previously reported cases of rodenticides poisoning, ANA-positive individuals are rare, and this kind of fluorescence pattern has not been reported before. CONCLUSIONS: During the diagnosis and treatment of anticoagulant rodenticides poisoning patients, the monitoring of coagulation function is important, but other laboratory tests should also be considered to avoid missing some suggestive positive results.

The Peritoneal Macrophages in Inflammatory Diseases and Abdominal Cancers.

Peritoneal macrophages (PMs) are the major cell type of peritoneal cells that participate in multiple aspects of innate and acquired immunity in the peritoneal cavity. PMs have an ability to release a large amount of proinflammatory and anti-inflammatory cytokines and therefore play a critical role in regulating the differentiation of innate immune cells and inflammatory T cells. Accumulating studies demonstrate that the immunological reactions and inflammatory responses of PMs are strongly related to the pathogenic processes of various inflammatory diseases and abdominal cancers. Consequently, the regulation of PM activation has gradually emerged as a promising target for immunotherapy, and better understanding of the distinctly biological function of PMs in individual diseases is crucial for designing specific and effective therapeutic agents. This review covers the characterization and immunological function of PMs in hosts with inflammatory diseases and abdominal cancers.

Structural maintenance of chromosomes 4 is required for leukemia stem cell maintenance in MLL-AF9 induced acute myeloid leukemia.

The gene, structural maintenance of chromosomes 4 (SMC4) plays important role in chromosomes condensing and mitotic sister chromatid segregation, which has been revealed in regulating multiple cancer development and carcinogenesis. However, the role of SMC4 in acute myeloid leukemia (AML) propagation and its function in regulation of leukemia stem cells (LSCs) is not yet clear. Using an MLL-AF9 induced AML mouse model, we demonstrated that down modulating of SMC4 expression could prolong the survival time of AML mice. Furthermore, we found that knockdown SMC4 expression decreased the proportion of LSCs and affected its leukemia-initiating capacity. Cell cycle assay demonstrated that more LSCs were arrested in G0 phase by SMC4 knockdown. This activity was accompanied by increased expression of the Cdkn1a (P21) and Cdkn1b (P27) as well as decreased expression of CDK4. Therefore, our study revealed the critical role of SMC4 during AML progression and provided new insights into the mechanism of LSC maintenance.

The effects of lead on GABAergic interneurons in rodents.

Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels ( p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox ( Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/ 2/ 5/ 6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.

PIG7 promotes leukemia cell chemosensitivity via lysosomal membrane permeabilization.

PIG7 localizes to lysosomal membrane in leukemia cells. Our previous work has shown that transduction of pig7 into a series of leukemia cell lines did not result in either apoptosis or differentiation of most tested cell lines. Interestingly, it did significantly sensitize these cell lines to chemotherapeutic drugs. Here, we further investigated the mechanism underlying pig7-induced improved sensitivity of acute leukemia cells to chemotherapy. Our results demonstrated that the sensitization effect driven by exogenous pig7 was more effective in drug-resistant leukemia cell lines which had lower endogenous pig7 expression. Overexpression of pig7 did not directly activate the caspase apoptotic pathway, but decreased the lysosomal stability. The expression of pig7 resulted in lysosomal membrane permeabilization (LMP) and lysosomal protease (e.g. cathepsin B, D, L) release. Moreover, we also observed increased reactive oxygen species (ROS) and decreased mitochondrial membrane potential (ΔΨm) induced by pig7. Some autophagy markers such as LC3I/II, ATG5 and Beclin-1, and necroptosis maker MLKL were also stimulated. However, intrinsic antagonism such as serine/cysteine protease inhibitors Spi2A and Cystatin C prevented downstream effectors from triggering leukemia cells, which were only on the "verge of apoptosis". When combined with chemotherapy, LMP increased and more proteases were released. Once this process was beyond the limit of intrinsic antagonism, it induced programmed cell death cooperatively via caspase-independent and caspase-dependent pathways.

Reference Intervals for Thyroid Function and the Negative Correlation between FT4 and HbA1c in Pregnant Women of West China.

BACKGROUND: It is necessary to establish the reference intervals of thyroid hormones in the three trimesters and postpartum period of healthy pregnant women in western China. Thyroid hormones play important roles in metabolic processes. METHODS: The concentrations of TPOAbs, TSH, and FT4 were measured by an ADVIA Centaur 2000 and HbA1c in the second trimester was measured by BIO-RAD D-10. RESULTS: 3435 pregnant women and 834 non-pregnant women were selected to establish the reference intervals. The level of TSH was the lowest (from 0.051 to 4.489 mIU/L) in the first trimester (p < 0.001) and FT4 was lower in the second (from 10.97 to 15.49 pmol/L) or third trimester (from 9.49 to 16.25 pmol/L) compared with the other periods (p < 0.001). 20% of participants had TSH levels below the lower limit of the manufacturer's reference interval (0.55 mIU/L) in the first trimester. 6.9% in the second and 16.1% of participants in the third trimester had FT4 levels below the lower limit of the manufacturer's reference interval. In multiple regression analyses, FT4 was independently associated with HbA1c (OR = 0.191; 95% CI 0.052, 0.698; p = 0.012), BMI (OR = 0.697; 95% CI 0.525, 0.927; p = 0.013), and TSH (OR = 0.647; 95% CI 0.428, 0.978; p = 0.039). Nonpredictive variable was age. CONCLUSIONS: The established reference intervals of TSH and FT4 reflected the changes of thyroid hormones veritably during gestation, and concentrations of FT4 in the first trimester were negatively correlated with HbA1c in the second trimester.

Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.

iASPP is a member of the apoptosis-stimulating proteins of p53 (ASPP) family and negatively regulates the apoptotic function of p53. In a hematopoietic system, overexpression of iASPP results in blockage of apoptosis, which may play a role in regulating hematopoietic stem cell (HSC) numbers. To address this, we first analyzed the expression of iASPP in patients with acute leukemia (AL) and found it was highly expressed in patients with AL. We further established a transgenic mouse model in which human iASPP was specifically expressed in hematopoietic cells. Overexpression of iASPP led to an increase in the proportion of long-term HSCs, short-term HSCs, multipotent progenitors, and common myeloid progenitor. HSCs from iASPP transgenic mice had an advantage in long-term reconstitution potential. In addition, the hematopoietic cells from iASPP transgenic mice exhibited a significantly lower level of p53 dependent apoptosis. After irradiation damage, hematopoietic cells of iASPP transgenic mice had a higher level of γ-H2AX expression, which lasted for a longer time. These results provide the first evidence that the iASPP can increase HSC populations and reconstitution capacity. Interestingly, in response to cell damage stimuli, hematopoietic cells can be protected against apoptosis by iASPP; meanwhile these apoptosis-resistant cells would have more mutation accumulation, which might be the potential risk for malignant transformation.-Jia, Y., Peng, L., Rao, Q., Xing, H., Huai, L., Yu, P., Chen, Y., Wang, C., Wang, M., Mi, Y., Wang, J. Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation.

Two cases of false platelet clumps flagged by the automated hematology analyzer Sysmex XE-2100.

BACKGROUND: Automated hematology analyzer is widely used by clinical laboratories to examine blood cell counts and differential leukocyte counts. However, a microscopic examination of a well-prepared blood film is still necessary and useful in most cases. METHODS: Two patients with severe disease were required complete blood counts (CBC) after admission at West China Second University Hospital in Southwest China. RESULTS: A false "platelet clumps?" flag was generated by the automated hematology analyzer Sysmex XE-2100. However, when the well-prepared blood film was reviewed, there was echinocytosis rather than clumps of platelets. In addition, both patients had severe metabolic acidosis with arterial blood pH <7.00 and HCO3- <4 mmol/l. On day 2 of admission, the false platelet clumps flags were not presented in both cases. CONCLUSIONS: Our further results suggested that the false platelet clumps had been flagged probably due to the influence of the extremely low blood pH. These two cases emphasized that a microscopic examination of a blood film was central to the morphology of blood cells. When the result of microscopic examination was abnormal, it was suggested that the physician should consider further testing to find underlying condition.

iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytes.

iASPP was an inhibitory member of ASPP family and could specifically inhibit the apoptotic function of p53. iASPPsv was identified by our lab as the short isoform of iASPP, which encoded a 407 aa protein and highly matched the carboxyl terminus of iASPP. In this study, iASPPsv was stably transfected into the breast cancer cell line MCF-7 by means of lentivirus to explore the effects of iASPPsv on biological functions of MCF-7. Thymocytes from iASPP/iASPPsv transgenic mice were also used to explore the effects of iASPP/iASPPsv on cell biological function. The results demonstrated that iASPPsv antagonized the growth inhibition induced by etoposide (VP-16) in MCF-7 cells. iASPPsv also down-regulated proapoptotic genes (Bax, Puma and Noxa) expression to inhibit apoptosis caused by VP-16. Moreover, iASPP and iASPPsv could both help the thymocytes of transgenic mice to resist the growth inhibition and apoptosis caused by dexamethasone (Dex) or VP-16. At the same time, DNA double strand break damage accumulated in either iASPPsv MCF-7 cells or iASPP/iASPPsv thymocytes. These findings showed that iAPSS/iASPPsv reduced the growth inhibition and apoptosis induced by Dex or VP-16, with DNA damage accumulating which might promote the pathogenesis and/or progression of cancer.

Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth.

Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.