An unusually high prevalence of allergic rhinitis at high altitudes in 6-7 year old children - An epidemiological study.

Objectives: To compare the epidemiology and disease patterns of allergic rhinitis (AR) at 2 different altitudes in children aged 6-7 years, and subsequently to compare with and augment data from international studies. Materials and methods: This is a multistage, clustered and stratified random sample study. The study area comprises 2 distinct areas within Yunnan Province, China. Low altitude was represented by Xishuangbanna Prefecture (XB), while high altitude was represented by Diqing Prefecture (DiQ). Each study area was subdivided into 3 sub-areas, and children aged 6-7 years were randomly sampled based on proportion-weighted sampling. The area studied includes the well-known area of Shangri-La city. Questionnaires were distributed and jointly completed by study participants and their parents or guardians, under the guidance of professional medical staff. Results: 2796 valid questionnaires out of 2933 distributed were obtained (survey response rate 95.3%). The prevalence of AR is statistically significantly higher at high altitude (DiQ, 36.0%, 95%CI 33.2-38.8) as compared to low altitude (XB, 19.7%, 95%CI 17.8-21.6) (p < 0.001). Both areas studied had a greater prevalence of AR compared to international data. In both XB and DiQ, male gender, history of early antibiotic use, urban place of birth and place of residence, presence of smokers within the same household, family history of allergic diseases (such as atopic dermatitis), as well as higher parental educational level were all associated with a higher prevalence of AR (p < 0.05). In DiQ, the prevalence of AR in Han ethnicity was greater than that of ethnic minorities (p < 0.05). In XB, being a single child was associated with an increased prevalence of AR compared to those who had siblings (p < 0.05). Conclusion: Our study found that the prevalence of AR is relatively greater at higher altitudes. Genetic and environmental factors both play an important role in the pathogenesis of AR. While altitude may be an important environmental factor, confounding factors may include humidity, temperature and distribution pattern of common aeroallergens.

[Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas: a multicenter clinical research protocol]. / é«˜æµ·æ‹”åœ°åŒºå¥åº·è¶³æœˆæ–°ç”Ÿå„¿è„‘æ°§ä»£è°¢åŠè„‘ç”µæ´»åŠ¨å·®å¼‚çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶æ–¹æ¡ˆ.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.

Pomolic acid and its glucopyranose ester promote apoptosis through autophagy in HT-29 colon cancer cells.

BACKGROUND: Colon cancer remains a leading cause of death globally. Pomolic acid (PA) can be separated from the ethyl acetate fraction of achyrocline satureioides. AIM: To determine the effects of PA and its glucopyranose ester, pomolic acid-28-O-ß-D-glucopyranosyl ester (PAO), on colon cancer HT-29 cells. METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to measure cell viability. Apoptosis was detected via hoechst 33342 staining. PI single staining was identified by flow cytometry to determine the cycle and scratch assay was used to observe the migration of HT-29 cells. The levels of mRNA and proteins were evaluated by q polymerase chain reaction and western blotting, respectively. RESULTS: PA and PAO considerably inhibited the growth of the HT-29 cell line in a time and dose-dependent manner. After the administration of PA and PAO for 24 and 48 h, cell apoptosis was significantly promoted and HT-29 cells were arrested in the G0/G1 stage. The Bax/Bcl2 ratio was also increased, which activated cysteinyl aspartate specific proteinase 3, leading to apoptosis; it also increased the expression of light chain 3 II/I and Beclin1, which activated autophagy and caused cell death. This in turn increased the expression of p62 to promote cell apoptosis, inhibiting the levels of signal transducer and activator of transcription 3 (STAT3) and p-STAT3, suppressing the level of Bcl2, and promoting cell. CONCLUSION: Both PA and PAO provide novel therapeutic strategies for treating colorectal cancer.

The Role of CT Scan in Pediatric Airway Foreign Bodies.

Objective: We aim to determine the utility of CT scan as a method to accurately confirm pediatric airway foreign bodies (AFBs), the current gold standard of which is chest X-ray as the primary imaging modality in the investigation screening of AFBs with progression to microlaryngobronchoscopy. Methods: A retrospective cohort study of children diagnosed with suspected AFBs between July 2019 and June 2020 was conducted. The primary outcome of missed AFBs from radiologic investigations was recorded. Results: A total of 226 children with an average age of 1.94 years were included in this study. One hundred and two children were eventually admitted to the hospital for microlaryngobronchoscopy. A total of 89 cases were initially examined by chest X-ray with the diagnosis confirmed in 26 cases. The initial examination was chest CT scan in 105 cases, of which the diagnosis was confirmed in 46 cases. The initial examination was chest CT scan with airway reconstruction in 32 cases, and the diagnosis was confirmed in 17 cases. Patients with negative chest CT scan with airway reconstruction were observed to have resolution of symptoms with no further need for bronchoscopy. Conclusion: Chest CT scan with airway reconstruction had the highest rate of confirmed diagnosis of pediatric AFBs on initial scanning, followed by chest CT scan, and finally chest X-ray with fluoroscopy; there was no missed diagnosis in chest CT scan with airway reconstruction. Chest CT scan with airway reconstruction can accurately and quickly detect AFBs and reduce unnecessary bronchoscopy.

The genes for sensory perception of sound should be considered in gene diagnosis of congenital sensorineural hearing loss and microtia.

Congenital sensorineural hearing loss (CSHL) and microtia are development-related diseases, sharing some factors and affecting children's hearing. However, genetic tests only focus on CSHL. We try to identify the common molecular mechanism of CSHL and microtia as candidates combining gene diagnosis biomarkers. Whole-exon sequencing (WES), Sanger sequencing, qPCR, and bioinformatics analyses were performed in microtia family (F1), family two, whose proband suffered from microtia and CSHL (F2), five microtia, and four CSHL individuals, respectively. We found that 40% microtia and 40% CSHL relevant genes were detected in F1 and a sharing pathway: the sensory perception of sound was identified. Moreover, the copy number variation in proband F2 was identified in one gene of the sharing pathway: EYA1. Meanwhile, two variants of BUB3 were identified in F1 data. BUB3 is related to development, dog ear type, direct and indirect interaction with microtia, and CSHL relevant genes. Notably, although the allele frequency of two variants of BUB3 showed significant differences between microtia and CSHL, the special microtia-relevant genotype also could be detected in one CSHL sample. These results suggest that the sensory perception of sound and the development of relevant pathways may be the common pathways of microtia and CSHL. Genes of these pathways can be used as candidates combining gene diagnosis biomarkers.

Memantine Promotes Bactericidal Effect of Neutrophils Against Infection with Pseudomonas aeruginosa and Its Drug-Resistant Strain, by Improving Reactive Oxygen Species Generation.

Pseudomonas aeruginosa is an opportunistic pathogen, which usually presents multiple antibiotic resistance. Host-directed therapy involves modulating the host defense system and the interplay between innate and adaptive immunity is a new strategy for designing anti-infection drugs. Memantine (MEM), a drug used to treat Alzheimer's disease, has a good inhibitory effect on neonatal mice with Escherichia coli-associated bacteremia and meningitis; however, the inhibitory effect and mechanisms of MEM against P. aeruginosa infection remain unclear. Here, we investigated whether MEM could inhibit P. aeruginosa infection and explored the potential mechanisms. MEM significantly promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain. The combination index of MEM and amikacin (AMK) was <1. In vivo experiments showed that the bacteremia and inflammation severities in the MEM-treated group were less than those in the untreated group, and the bacterial load in the organs was significantly less than that in the control group. Combining MEM with the reactive oxygen species (ROS) inhibitor, N-acetyl-l-cysteine, weakened the anti-infective effect of MEM. MEM increased the expression of NADPH p67phox and promoted neutrophilic ROS production. Deleting the p67phox gene significantly weakened the effects of MEM on ROS generation and improving bactericidal effect of neutrophils. In conclusion, MEM promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain, and had a synergistic antibacterial effect when combined with AMK. MEM may exert its anti-infective effects by promoting neutrophilic bactericidal activity via increasing the expression level of p67phox and further stimulating ROS generation.

Progress in prevention and control of Nipah virus disease / 中华流行病学杂志

Nipah virus disease (NVD) is a newly emerged zoonosis with a case fatality rate of 40%-75%. NVD is a severe threat to human health and the development of livestock farming. NVD has become one of the emerging infectious diseases with great concern globally during more than 20 years. Nipah virus (NiV) is a pathogen for NVD, the natural host of which is Fruit bats of the Pteropodidae family. The clinical spectrum of NiV infection is broad, including asymptomatic infection, acute respiratory infection, fatal encephalitis, and even death. Since NiV was first identified in Malaysia in 1999, it has been prevalent mainly in Southeast Asia and South Asia. NiV is primarily transmitted to humans through bat-pig-human, contaminated food. Currently, there are no specific therapeutic drugs and vaccines for NVD. Although there are no cases of NVD reported in China, which has close personnel and trade exchanges with major NVD-endemic countries, and NiV antibody has also been detected in relevant bats. There is a potential risk of importing NVD and domestic outbreaks in the future in this country. This paper provides a systematic review of the research progress in the prevention and control of NVD etiology, epidemiology, clinical manifestations and laboratory diagnosis to help relevant staff to understand NVD more comprehensively and systematically.

Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort / 中华预防医学杂志

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.

Analysis on characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive after discharge in Guangdong Province / 中华预防医学杂志

Objective: To analyze the epidemiological characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive in anal and/or throat swabs after discharge during the domestic imported epidemic stage in Guangdong Province in early 2020. Methods: The COVID-19 confirmed cases with the onset time before March 1, 2020 in Guangdong Province were collected to analyze the demographic data, epidemiological characteristics, and specimen collection and testing data after discharge. Logistic regression model was used for influencing factors analysis of re-positive cases. Results: A total of 1 286 COVID-19 confirmed cases were included, the M(Q1,Q3) of age was 44(32,58)years, 617 cases were male, 224 cases were re-positive in anal and/or throat swabs with the re-positive rate 17.42%. The M(Q1,Q3) of age of re-positive cases was 35(23, 50) years, which was younger than that of re-negative cases age was those 46(33, 59) years (P<0.001). With the increase of age, re-positive rate decreased (χ2trend=52.73, P<0.001). 85.27% (191/224) of re-positive cases were found in 14 d after discharge, the duration time of re-positive status was 13(7, 24) d, and 81.69% (183/224) of re-positive cases were re-tested negative in 28 d after re-positive date. No fever and other symptoms had been observed among re-positive cases during the whole follow-up. No secondary infectious cases had been found among close contacts after 14 d of centralized isolation and sampling screening. Univariate logistic regression model analysis revealed that the influencing factors of the re-positive cases included age, occupation, clusters, clinical types, and admission time. Multivariate logistic regression model analysis revealed that age was an independent risk factor. Conclusions: SARS-CoV-2 viral nucleic acid re-positive is found in COVID-19 confirmed cases after discharge in Guangdong Province. Most re-positive cases are confirmed among 14 d after discharge and re-test to negative among 28 d after re-positive date. Age is an risk factor for re-positive cases after discharge.

Cooperative work and mechanism in the COVID-19 containment action by the support-to-Hebei epidemiological investigation group formed by five provinces / 上海预防医学

ObjectiveTo understand the cooperative work and mechanism in the corona virus disease 2019 containment action by the support-to-Hebei epidemiological investigation group formed by five provinces， summarize the existing challenges， and discuss the relevant mechanism， so as to provide evidence for future support actions. MethodsA questionnaire survey was used to investigate the members from five provinces of the support-to-Hebei epidemiological investigation team. The content included basic information， work situation， problems in cooperative work， and suggestions in support mechanisms. ResultsA total of 104 questionnaires were issued， of which 101 valid questionnaires were collected with an effective response rate of 97.12%. The proportions of respondents who participated in the epidemic-related data preparation， case investigation， technical training， supervision of key venues， and specimen collection was 93.07%， 85.15%， 81.19%， 65.35%， and 44.55%， respectively. The respondents believed that information sharing channel of local epidemic situation was blocked （95.05%）， coordination mechanism among local departments was insufficient （84.16%）， communication and coordination mechanism among the dispatch institutions， support team， and local departments was unperfect （84.16%）， management of the dispatch institutions to the support team was relatively loose （79.21%）， dispatch institutions failed to make full use of professional advantages of the support team （72.28%）， and majority of the support team members engaged in a single profession （59.41%）. The respondents suggested that local departments should improve the information sharing mechanism （95.05%）， strengthen communication and coordination among the dispatch institutions， support team， and local departments （92.08%）， and dispatch institutions should clarify the tasks and responsibilities of the support team （91.09%）， formulate cross-regional emergency support plans （87.13%） and evaluation plans of support action （72.28%）. ConclusionIn order to ensure the efficiency and accuracy of future support actions， it is necessary to improve the mechanism of emergency coordination， communication and matching， response procedures， team management， and support evaluation.

A clinical study on the tip localization of peripherally inserted central catheter (PICC) guided by intracavitary electrocardiography in newborns: a randomised trial.

BACKGROUND: The present study aimed to investigate the P-wave changes in intracavitary electrocardiography (IC-ECG) during catheterization with a peripherally inserted central catheter (PICC) in order to provide guidance for the accurate localization of the tip of the PICC. METHODS: A total of 106 newborns who needed a PICC were randomly divided into two groups-a study group and a control group-using a random number table, with 53 cases in each group. In the study group, the ECG monitor was connected after the successful puncture and insertion of the PICC into the right sternoclavicular joint, and the position of the catheter tip was determined according to the P-wave changes on the IC-ECG. Localization X-rays were taken at the same time. In the control group, after the successful routine puncture and insertion of the PICC into the location to a predetermined length, localization X-rays were taken. The accuracy, procedure duration, and cost of the two localization methods were evaluated. RESULTS: The accuracy of the localization in the study group was 92.5%, but the difference was not significant when compared with the control group (P>0.05). The duration of the procedure in the study group was 5.12±1.57 minutes, and the cost was 7.12±0.56 yuan, both of which were significantly different when compared with the control group (P<0.05). CONCLUSIONS: P-wave changes during IC-ECG have high accuracy in determining the location of the tip of the PICC. It is also a simple method and has certain clinical application value. TRIAL REGISTRATION: Chinese Clinical Trial Registry (number: ChiCTR2100047660).

Waardenburg syndrome type II in a Chinese pedigree caused by frameshift mutation in the SOX10 gene.

Waardenburg syndrome (WS) is a congenital hereditary disease, attributed to the most common symptoms of sensorineural deafness and iris hypopigmentation. It is also known as the hearing-pigmentation deficient syndrome. Mutations on SOXl0 gene often lead to congenital deafness and has been shown to play an important role in the pathogenesis of WS. We investigated one family of five members, with four patients exhibiting the classic form of WS2, whose DNA samples were analyzed by the technique of Whole-exome sequencing (WES). From analysis of WES data, we found that both the mother and all three children in the family have a heterozygous mutation on the Sex Determining Region Y - Box 10 (SOX10) gene. The mutation was c.298_300delinsGG in exon 2 of SOX10 (NM_006941), which leads to a frameshift of nine nucleotides, hence the amino acids (p. S100Rfs*9) are altered and the protein translation may be terminated prematurely. Further flow cytometry confirmed significant down-regulation of SOX10 protein, which indicated the SOX10 gene mutation was responsible for the pathogenesis of WS2 patients. In addition, we speculated that some other mutated genes might be related to disease phenotype in this family, which might also participate in promoting the progression of WS2.

Analysis of genetic characteristics in two Chinese children of type Ⅱ Waardenburg syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To screen and analyze the mutations of MITF gene in two children of type Ⅱ Waardenburg syndrome (WS2) from different families in Yunnan,China,and to explore the possible molecular pathogenesis. Methods: With informed consent, medical history collection, physical examinations, audiological evaluation, and high resolution computer tomography (HRCT) scan of temporal bone were performed on the two WS2 probands and their family members. Genomic DNA was extracted from peripheral blood of all individuals. The coding regions including all exons, part of introns and promoters of MITF, PAX3, SOX10, SNAI2, END3, ENDRB, and KITLG genes were sequenced by high-throughput sequencing. According to the results of high-throughput sequencing, pathogenic mutations detected in the probands and their parents were verified by Sanger sequencing. Results: The proband 1 carried c.641_643delGAA mutation in the 7th exon of MITF gene, which was a frame-shift mutation resulting in an amino acid change of p.214delR. It was a de novo mutation as the parents of proband 1 showed no variation on this site. The proband 2 carried heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene, which defected the function of MITF protein. Conclusion: Genetic examinations provide important evidence for diagnosis of Waardenburg syndrome. Heterozygous mutation c.641_643delGAA and heterozygous loss of the large fragment ranging from exon 1 to exon 9 of MITF gene might be the molecular pathogenesis of the two WS2 probands in this study.

Identification and genetic analysis of new mutations in EYA1 gene of BOS syndrome / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis. Methods: Clinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing. Results: There were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) in EYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family. Conclusions: A novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.

Parkin: an Extremely Versatile E3 Ubiquitin Ligase / 中国生物化学与分子生物学报

Parkin, also known as PARK2, has been closely related to Parkinson's disease (PD) since its discovery. It is considered to be a neuroprotective gene. With the in-depth understanding for its structure, Parkin has been unveiled as an E3 ubiquitin ligase. Parkin is involved in the regulation of cell cycle, mitochondrial homeostasis, energy metabolism and other cellular processes, and is closely related to many diseases. It even plays completely opposite roles in the same pathway, namely cell proliferation and apoptosis, indicating that this must be a gene with an extremely broad and important role. This article summarizes the discovery and structure of Parkin and its self-inhibiting characteristics, focusing on the ubiquitination process that it participates in as E3 ubiquitin ligase and the resulting autophagy, protein degradation, changes in protein subcellular localization and protein interaction. These may all serve as the basis for Parkin to prevent PD and suppress tumors. On this basis, two reasons for Parkin abnormalities leading to PD are summarized: abnormal protein quality control and mitochondrial dysfunction, and extended to cardiovascular and kidney diseases caused by the abnormality of Parkin due to mitochondrial dysfunction. The internal connection between Parkin and cancer is also introduced from the aspects of Parkin as a tumor suppressor, regulating cell cycle, apoptosis and metastasis, oxidative stress and energy metabolism. By maintaining the active state of Parkin or enhancing its expression, it may be possible to improve the condition of PD patients. But the mechanism of Parkin's inhibition of tumor growth remains to be deciphered, and the potential role of Parkin in mediating the relationship between PD and cancer risk should be strengthened. These follow-up in-depth studies and their role in the diagnosis and treatment of related diseases and application of target molecules laid the foundation.

How Can We Do Better? Learning From 617 Pediatric Patients With Airway Foreign Bodies Over a 2-Year Period in an Asian Population.

Background: Foreign body (FB) in the pediatric airway is a prevailing and crucial emergency with presenting symptoms often overlapping with other common pediatric conditions. There are limited number of large cohort studies in an Asian population which demonstrate the diversity of symptoms, investigations which will aid in obtaining the diagnosis, and management. Using this large cohort, we aim to evaluate the type and location, clinical presentations and outcomes of medical management related to pediatric airway FB in an Asian society. Methods: This is a retrospective study of all airway FB treated in Kunming Children's Hospital, China from February 2016 to June 2019. Six hundred and thirty-two clinical and operative records of all airway FB were retrieved and reviewed from the hospital's central electronic medical records. A total of 617 patients were included in our study. Results: The age ranged from 4 months to 12 years (mean = 1.74 years). The duration of symptoms ranged from 1 h to 605 days, with the diagnosis established at an average 9.16 days. Almost all had multiple symptoms, most commonly cough (98.5%) followed by noisy breathing (98.2%). Majority of the FBs (95.5%) were organic and the rest inorganic. Of the organic FBs, peanut was the most common (31.6%), followed by walnut (13.3%) and sunflower seeds (9.2%). Comparatively, 80.8% of the organic FBs were retrieved incomplete while 85.7% of the inorganic FBs were completely intact. Multiple FBs were noted in 43.3% of the patients, with 2.4% of them in different locations. Conclusions: Airway FB can be easily missed with resultant delay in diagnosis. In an Asian population, walnut and sunflower/pumpkin seeds feature more prominently compared to Western populations. Sunflower seed FBs tend to present earlier and are found intact in the trachea. Rigid bronchoscopy is the most common technique used to remove such FBs and pulmonary-related complications post-operatively, though rare, are the most common adverse outcomes. Preventive strategies targeting the appropriate age group and this type of FB may be useful in an Asian population.

Rapid evaluation of neutralizing antibodies in COVID-19 patients

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for a method to rapidly and conveniently evaluate neutralizing antibody (NAb) activity in patients. Here, an up-conversion phosphor technology-based point-of-care testing (UPT-POCT) and a microneutralization assay were employed to detect total antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and NAb activity in COVID-19 patients sera, respectively, in order to determine if UPT-POCT could be used as a surrogate method for rapid evaluation of serum NAb activity in COVID-19 patients. In total, 519 serum samples from 213 recovered and 99 polymerase chain reaction re-positive (RP) COVID-19 patients were used in this report. We found that UPT-POCT reporting values correlated highly with NAb titers from 1:4 to 1:1024, with a correlation coefficient r = 0.9654 (P < 0.001), as well as protection rate against RP (r = 0.9886, P < 0.0001). As a significant point for reducing re-positive rate, UPT-POCT values of 4.380 {+/-} 2.677, corresponding to NAb titer of 1:64, may be appropriate as an indicator for evaluating high efficiency of protection. This study demonstrates that the quantitative lateral flow based UPT-POCT, could be used to rapidly evaluate NAb titer, which is of importance for assessing vaccine immunization efficacy, herd immunity, and screening patient plasma for high NAbs.

Clinical, immunological and virological characterization of COVID-19 patients that test re-positive for SARS-CoV-2 by RT-PCR

BackgroundCOVID-19 pandemic is underway. Some COVID-19 cases re-tested positive for SARS-CoV-2 RNA after discharge raising the public concern on their infectivity. Characterization of re-positive cases are urgently needed for designing intervention strategies. MethodsClinical data were obtained through Guangdong COVID-19 surveillance network. Neutralization antibody titre was determined using a microneutralization assay. Potential infectivity of clinical samples was evaluated after the cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing. ResultsAmong 619 discharged COVID-19 cases, 87 were re-tested as SARS-CoV-2 positive in circumstance of social isolation. All re-positive cases had mild or moderate symptoms in initial diagnosis and a younger age distribution (mean, 30.4). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=150) parallel-tested in this study. No infective viral strain could be obtained by culture and none full-length viral genomes could be sequenced for all re-positive cases. ConclusionsRe-positive SARS-CoV-2 was not caused by the secondary infection and was identified in around 14% of discharged cases. A robust Nabs response and a potential virus genome degradation were detected from nearly all re-positive cases suggesting a lower transmission risk, especially through a respiratory route.

Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

Genomic epidemiology of SARS-CoV-2 in Guangdong Province, China

COVID-19 is caused by the SARS-CoV-2 coronavirus and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, Chinas most populous province, during early 2020 resulted in 1,388 reported RNA positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain due to low virus genetic variation early in the pandemic. Our results illustrate how the timing, size and duration of putative local transmission chains were constrained by national travel restrictions and by the provinces large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required as the number of cases imported from other countries is increasing. HighlightsO_LI1.6 million molecular diagnostic tests identified 1,388 SARS-CoV-2 infections in Guangdong Province, China, by 19th March 2020 C_LIO_LIVirus genomes can be recovered using a variety of sequencing approaches from a range of patient samples. C_LIO_LIGenomic analyses reveal multiple virus importations into Guangdong Province, resulting in genetically distinct clusters that require careful interpretation. C_LIO_LILarge-scale epidemiological surveillance and intervention measures were effective in interrupting community transmission in Guangdong C_LI