Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Stability of a rat model of prehepatic portal hypertension caused by partial ligation of the portal vein

AIM： To study the stability of portal hypertension （PHT） caused by partial ligation of the portal vein ligation （PVL） in a rat model.METHODS： Thirty male adult Wistar rats were divided into two groups： 10 in Group Ⅰ received a sham operation; and 20 in Group Ⅱreceived partial PVL. Portal vein pressure （PVP） was measured at four time periods： before ligation, 2 wk, 6 wk and 10 wk postsurgery. Portal venography, blood sampling and liver and spleen pathological examinations were conducted at 10 wk after surgery.RESULTS： The PVP was 9.15± 0.58 cmH2O before ligation, and increased to 17.32 ±0.63 cmH2O 2 wk after PVL. By repeat measurement of the PVP in each rat, it was shown to remain elevated for 10 wk. There were no significant differences in the pressure measurements at 2 wk, 6 wk and 10 wk. Varices were found mainly in the mesenteric vein 2 wk after PVL, which were more obvious later, while these manifestations were similar at week 6 and week 10. Portal venography demonstrated the varices and collaterals. There was no significant change in liver pathology. The volume of the spleen was enlarged 2-fold after ligation, and the sinus of the spleen was enlarged due to congestion. Significant sinus endothelial cell proliferation was observed, but no evidence of hypersplenia was found on hemogram and biochemical examination.CONCLUSION： These findings suggest that a satisfactory prehepatic PHT rat model can be obtained by partial ligation of the portal vein, and this PHT rat model was stable for at least 10 wk.

Relations between lymphangiogenesis and the size of pterygium

AIM: To examine the relations between lymphangiogenesis and the size of pterygium. METHODS: Tissues from 88 primary and 34 recurrent pterygia were evaluated, and those from 7 nasal epibulbar conjunctiva segments were used as controls. Pterygium slices from each patient were stained with LYVE-1 monodonal antibodies to identify lymphatic microvessel for calculating lymph-vascular area (LVA), lymph-microvascular density (LMD) and lymph-vascular luminal diameter (LVL). Also, the relations between lymphangiogenesis (measuring by LVA, LMD and LVL) and the size of pterygium (extension, width and area) were explored. RESULTS: There were a few LYVE-1 ((+)) lymphatic vessels in normal epibulbar conjunctiva segments. However, the number of lymphatic vessels slightly increased in primary pterygia and dramatically increased in recurrent pterygia. LVA, LMD and LVL significantly increased in recurrent pterygia in comparison with primary pterygia (all P<0.05). Both LMD and LVA were correlated with the width and area of pterygia (both P<0.05), and LVA was also correlated with the extension of pterygia(P<0.05). CONCLUSION: Lymphangiogenesis is correlated with the size of pterygium. The outgrowth of lymphatic vessels might contribute to the development of pterygia.

Relationship between angiogenesis and lymphangiogenesis in recurrent pterygium

AIM: To examine the relationship between angiogenesis and lymphangigenesis in recurrent pterygia. METHODS: Tissues from 34 excised recurrent pterygia (including 12 Grade 1, 10 Grade 2, and 12 Grade 3) were involved in the study and tissues from 7 nasal epibulbar conjunctivae segments were used as controls. Sections from each pterygium were immunostained with CD31 and LYVE-1 monoclonal antibodies to evaluate lymphatic microvessel density (LMVD) and blood microvessel density (BMVD), and the relationship between LMVD and BMVD in the pterygium was examined. RESULTS: There was a large number of CD31(+) LYVE-1((-)) blood vessels but only a few CD31 (+)LYVE-1 ((+)) lymphatic vessels in grades 1 and 2 pterygium. However, lymphatic vessels were dramatically increased in grade 3 pterygium. LMVD correlated dosely with BMVD in all pterygia, including grades 1, 2 and 3 peterygium patients (all P values < 0.01). Although both the density of blood and lymphatic vessels increased in recurrent pterygia, lymphatic vessels developed much faster than blood vessels, especially in grade 3 pterygia. CONCLUSION: There is a significant but not parallel relationship between angiogenesis and lymphangiogenesis in recurrent pterygium. The outgrowth of blood and lymphatic vessels provide evidence that immunological mechanism may play a role in the development and recurrence of pterygium.

Recombinant human erythropoietin for repair of white matter damage

Erythropoietin has been shown to exhibit neuroprotective effects in animal models. A neonatal rat model of hypoxic-ischemic white matter damage was established via bilateral carotid artery ligation in 4-day-old Sprague-Dawley rats. The rats were subsequently treated with recombinant human erythropoietin to observe pathological changes in the brain and long-term neurobehavioral functions before and after intervention. Results showed that the number of myelin basic protein-positive cells, which reflected myelin/oligodendrocyte damage, significantly increased, although the number of amyloid precursor protein-positive cells, which reflected axonaf injury, significantly decreased in periventricular white matter at 72 hours and 7 days following erythropoietin intervention. The number of glial fibrillary acidic protein-positive cells, indicating astrocytic damage, significantly decreased in periventricular white matter of erythropoietin-treated rats at 48 hours, 72 hours, 7 days and 26 days. Following erythropoietin intervention in the 30-day-old rats, head-turning time in the slope test was shortened and open-field test scores increased. These results suggested that erythropoietJn promoted repair of white matter damage, as well as improved neurobehavioral functions in a rat model of hypoxic-ischemic injury.

Magnetic resonance imaging diagnosis of acute Guillain-Barré syndrome in children

The present study examined 24 children with acute Guillain-Barre syndrome using magnetic resonance imaging （MRI） plain scans and fat-suppressed enhanced Tl-weighted imaging （T1WI） scans. Axial MRI plain scans centering on the medullary conus were positive in nine patients （38%）. These displayed variable thickening involving the cauda equina with isointensity on T1WI and isointensity or slight hyperintensity on T2WI. False negatives were obtained in patients with cervical and cranial nerve symptoms. Contrast enhancement of T1WI with fat suppression was positive in all patients in the cauda equina with varied thickening and enhancement centering on the medullary conus. Five patients （36%） were positive in the cervical nerves and 3 patients （50%） were positive in the cranial nerves. These patients had corresponding cervical and cranial nerve symptoms, respectively. Patients with serious clinical symptoms in the lower limbs exhibited obvious involvement of the cauda equina by MRI. Statistical analysis revealed a positive correlation between the extent of enlargement of the cauda equina, centering on the medullary conus, and cerebrospinal fluid protein concentration.

Prevalence of antimicrobial resistance of Streptococcus pneumoniae in Chinese children: four hospitals surveillance

Objective To investigate the nasal carriage of antibiotic-resistant pneumococci in children of < 5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi' an.Methods A total of 647 pneumococci strains were isolated and detected. Minimal inhibition concentrations (MICs) of antibiotics were determined by E-test. Disk diffusion test was used for the measurement of antimicrobial susceptibility.Results Prevalence of penicillin non-susceptible Streptococcus pneumoniae in the four cities was 41%, with Guangzhou (60.8%) ranking first, followed by Xi' an (45%), Shanghai (37%) and Beijing (25. 9%). The majority of penicillin non-susceptibility isolates (23. 9% -53. 8%) had a low level of resistance (MIC 0. 64 -1. 5 μg/ml). The most sensitive antimicrobials in terms of percentage of susceptible organisms were amoxicillin-clavulanic acid ( 99.4%), followed by ceftriaxone (92. 1 %); cefurxime and cefaclor were slightly more sensitive than penicillin with susceptibility of 74. 8% and 77. 9%. Erythromycin, tetracycline and TMP-SMZ were highly resistant (83. 6% , 82. 1% and 76.2% respectively) . Among erythromycin resistant isolates, 100% were resistant to azithromycin, 98.6% to clarithromycin, 97.2% to roxithromycin and spiramycin, and 96.6% to clindamycin. 97.2% (141/145) were typical of the macrolides-lincosamides-streptogramons B (MLSB ) resistance phenotype, and 2. 8% (4/145) were M phenotype. The group of PRSP was with significantly higher rates of non-susceptibility for ceftriaxone (18. 4%), cefurxime (58. 6%), cefaclor (53. 4%), compared with the group of PEN-S (0. 5% , 1.8% and 0. 2% , respectively) and the rate of multi-drug resistance in the isolates of PRSP group (92. 9%) was significantly higher than that of PEN-S group (59.2%).Conclusion The rates of penicillin and multi-drug resistance among isolates of pneumococci carried nasally in are high children and the high prevalence of multi-drug resistance in the Chinese population may be becoming one of the most serious problems in this century.

Epidemiology of respiratory distress and the illness severity in late preterm or term infants： a prospective multi-center study

Background The severity of respiratory distress was associated with neonatal prognosis. This study aimed to explore the clinical characteristics, therapeutic interventions and short-term outcomes of late preterm or term infants who required respiratory support, and compare the usage of different illness severity assessment tools.Methods Seven neonatal intensive care units in tertiary hospitals were recruited. From November 2008 to October 2009, neonates born at ≥34 weeks＇ gestational age, admitted at 〈72 hours of age, requiring continuous positive airway pressure （CPAP） or mechanical ventilation for respiratory support were enrolled. Clinical data including demographic variables, underlying disease, complications, therapeutic interventions and short-term outcomes were collected. All infants were divided into three groups by Acute care of at-risk newborns （ACoRN） Respiratory Score 〈5, 5-8, and 〉8.Results During the study period, 503 newborn late preterm or term infants required respiratory support. The mean gestational age was （36.8±2.2） weeks, mean birth weight was （2734.5±603.5） g. The majority of the neonates were male （69.4%）, late preterm （63.3%）, delivered by cesarean section （74.8%）, admitted in the first day of life （89.3%） and outborn （born at other hospitals, 76.9%）. Of the cesarean section, 51.1% were performed electively. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score 〈7 at 5 minutes and resuscitated with intubation, the in-hospital mortality increased significantly. In total, 58.1% of the patients were supported with mechanical ventilation and 17.3% received high frequency oscillation. Adjunctive therapies were commonly needed.Higher rate of infants in severe group needed mechanical ventilation or high frequency oscillation, volume expansion,bicarbonate infusion or vasopressors therapy （P 〈0.05）. The incidence of complications was also increased significantly in severe group （P 〈0.05）. The in-hospital mortality in the severe group was significantly higher than other two groups （P〈0.05）. ACoRN Respiratory Score was correlated with Score for Neonatal Acute Physiology-Version Ⅱ （SNAP-Ⅱ） （P〈0.01）. High gestational age, high SNAP-Ⅱ score and oxygenation index （OI）, and Apgar score at 5 minutes 〈5 were independent risks for death.Conclusions Neonatal respiratory distress is still a common cause of hospitalization in China. Illness severity assessment is important for the management. ACoRN Respiratory Score which correlated with SNAP-Ⅱ score is easy to use and may be helpful in facilitating the caregivers in local hospital to identify the early signs and make the transfer decision promptly.

Epstein-Barr virus-encoded RNAs as a survival predictor in nasopharyngeal carcinoma

Background Epstein-Barr virus （EBV） infection is one of the most important factors of nasopharyngeal carcinoma （NPC）endemic areas.Transcription of EBV-encoded non-polyadenylated RNAs （EBERs） are presented in most of NPC tumors.Exploring EBERs as a prognostic marker for NPC might further be informative about the biology and the progression of the disease.The aim of this study was to analyze the role of EBV latency in the clinical management of nasopharyngeal carcinoma （NPC）,by detecting EBERs.Methods RNA in situ hybridization （ISH） for detecting EBERs was carried out on 908 NPC tumor tissues.Overall survival （OS） curves were analyzed with the Kaplan-Meier method and the Cox proportional-hazards regression models.Results The median follow-up time was 70 months （1-120 months）.Eight hundred and sixteen （89.9％） from a total of 908 consecutive NPC cases were found to be EBV-EBER positive.EBER-ISH staining revealed nuclear localization in NPC cells.In the Kaplan-Meier analysis for OS,high EBER expression levels in NPC patients were statistically significant positive prognostic factors for survival （log-rank,P=0.022）,especially in adults aged 17-40 years （P=0.023） and in those with advanced stage disease （log-rank,P=0.002）.Cox proportional-hazards regression model analysis showed that the EBER expression level was an independent risk factor for OS （hazard ratio 0.724,P=0.005）.Conclusions EBERs were frequently detected in NPC tumor tissues,and high-level EBER expression correlated with good prognosis in NPC patients,especially in adult patients and in those with advanced stage disease.EBER may serve as a potential prognostic predictor in NPC.

Clinical and laboratory features,treatment,and outcomes of macrophage activation syndrome in 80 children:a multi-center study in China

Background Macrophage activation syndrome(MAS)is a major cause of morbidity and mortality in pediatric rheumatology.We aimed to further understand the clinical features,treatment,and outcome of MAS in China.Methods A multi-center cohort study was performed in seven hospitals in China from 2012 to 2018.Eighty patients with MAS were enrolled,including 53 cases with systemic juvenile idiopathic arthritis(SJIA-MAS),10 cases of Kawasaki disease(KD-MAS),and 17 cases of connective tissue disease(CTD-MAS).The clinical and laboratory data were collected before(pre-),at onset,and during full-blown stages of MAS.We compared the data among the SJIA-MAS,KD-MAS,and CTD-MAS subjects.Results 51.2%of patients developed MAS when the underlying disease was first diagnosed.In patients with SJIA,22.6%(12/53)were found to have hypotension before the onset of SJIA-MAS.These patients were also found to have significantly increased aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),as well as decreased albumin(P<0.05),but no difference in alanine aminotransferase,ferdtin,and ratio of ferritin/erythrocyte sedimentation rate(ESR)at onset of MAS when compared to pre-MAS stages of the disease.In addition,ferritin and ratio of ferritin/ESR were significantly elevated in patients at full-blown stages of SJIA-MAS compared to pre-MAS stage.Significantly increased ferritin and ratio of ferritin/ESR were also observed in patients with SJIA compared to in KD and CTD.Receiver-operating characteristic analysis showed that 12,217.5μg/L of ferritin and 267.5 of ferritin/ESR ratio had sensitivity(80.0%and 90.5%)and specificity(88.2%and 86.7%),respectively,for predicting full-blown SJIA-MAS.The majority of the patients received corticosteroids(79/80),while biologic agents were used in 12.5%(10/80)of cases.Tocilizumab was the most commonly selected biologic agent.The overall mortality rate was 7.5%.Conclusions About half of MAS occurred when the underlying autoimmune diseases(SJIA,KD,and CTD)were first diagnosed.Hypotension could be an important manifestation before MAS diagnosis.Decreased albumin and increased AST,LDH,ferritin,and ratio of ferritin/ESR could predict the onset or full blown of MAS in patient with SJIA.

CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural Tube Defects

The protein composition of cerebrospinal fluid（CSF） in neural tube defects（NTDs） remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation（iTRAQ）. We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs.We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, andapolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.