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.

[Vitamin D level in children with bloodstream infection].

OBJECTIVE: To investigate the difference in serum 25(OH)D level between children with bloodstream infection and healthy children. METHODS: A case-control study was conducted among 60 children with bloodstream infection who were hospitalized between January 2010 and December 2013 and had positive results of two blood cultures. Meanwhile, 60 aged-matched healthy children who underwent physical examination during the same period of time were enrolled as the healthy control group. Chemiluminescence was applied to measure the serum 25(OH)D level, and the constituent ratios of children with different serum 25(OH)D levels were compared between the two groups. RESULTS: The bloodstream infection group had a significantly lower serum 25(OH)D level than the healthy control group (P<0.01). Compared with the healthy control group, the bloodstream group had significantly lower constituent ratios of children with normal Vitamin D level (8% vs 35%) or vitamin D insufficiency (22% vs 43%) (P<0.05). Compared with the healthy control group, the bloodstream group had significantly higher constituent ratios of children with vitamin D deficiency (42% vs 13%) or severely vitamin D deficiency (28% vs 8%) (P<0.01). CONCLUSIONS: Vitamin D insufficiency prevails among children, and children with bloodstream infection have a significantly lower serum 25(OH)D level than healthy children.

[NEMO Delta 4-10 deletion of NEMO gene in Chinese incontinentia pigmenti cases].

OBJECTIVE: Incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. In IP, mutations in NEMO lead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. Recently, a second nonfunctional copy of the gene, Delta NEMO was identified, opposite in direction to NEMO. Almost 90% of IP whose gene mutation type had been recognized have a recurrent genomic deletion of exons 4-10 of the NEMO (IKK gamma) gene, called NEMO Delta 4-10, which is necessary to activate the NF-kB pathway. Therefore, PCR-based detection of the NEMO deletion is a diagnostic measurement for IP. This study sought to analyze the NEMO Delta 4-10 deletion in NEMO gene of Chinese IP cases. METHODS: Seven IP cases and part of their families totally 15 persons were enrolled in this study. The 7 IP cases were aged 41 days to 8 years. Among them 1 was male and 6 were female. Four cases had family history of IP, the other 3 were sporadic cases. Fifty healthy children without any congenital diseases were taken as normal control group. According to the gene characteristics of IP, by PCR measurement NEMO Delta 4-10 deletion in NEMO gene was tested with specific primers In2/JF3R, and NEMO Delta 4-10 deletion in pseudogene Delta NEMO was checked out by primers Rev-2/JF3R. RESULTS: Five out of the 7 tested cases (case 1, 2, 3, 4, and 6) showed NEMO Delta 4-10 deletion in NEMO gene. The mothers of case 1 and case 6, 1a and 6a, also suffered from this disease, and their results were just the same as their daughters. For pseudogene Delta NEMO only case 2 and case 4 were proved having NEMO Delta 4-10 deletion, while other cases and families had negative results. For normal control group, NEMO Delta 4-10 deletion was not found either in NEMO gene or in their pseudogene Delta NEMO. CONCLUSION: Incontinentia pigmenti in most cases were caused by NEMO Delta 4-10 deletion in NEMO gene.

[The expression of connective tissue growth factor in renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin].

OBJECTIVE: To investigate the connective tissue growth factor (CTGF) mRNA expression in the renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. METHODS: Twenty-four rats underwent operation 2 times: during the first operation 2/3 of the left kidney was resected, and the right kidney was resected completely one week after. The 24 5/6 nephrectomized rats were randomly divided into 2 groups: untreated 5/6 nephrectomized group (model group, n=12) and fluvastatin-treated 5/6 nephrectomized group (treatment group, fluvastatin was orally administered 7 mg.kg(-1).d(-1) for 13 weeks, n=12), and 6 sham-operated rats served as control (sham operation group). In the weeks 2, 4, 8, and 13 after the second operation metabolic cage was used to collect the 24-hour urine 2 times. Urine protein was examined by biuret reaction so as to calculate urinary protein excretion. By the end of experiment blood was collected to examine the serum cholesterol, triglyceride, urea nitrogen, and creatinine contents. The rats were killed and their kidneys taken out. The CTGF mRNA expression in the renal cortex was detected by RT-PCR. Immunohistochemistry was used to examine the expression of transforming growth factor-beta1 (TGF-beta1), type IV collagen and fibronectin in the glomeruli. Renal pathological changes and glomerular sclerosis index (GSI) were evaluated as well. RESULTS: At the end of the experiment, the mean urinary protein excretion in the model group was 305.4 mg/24 h, significantly higher than that in the treatment group (230.9 mg/24 h, P<0.01) and the sham operation group (5.6 mg/24 h, P<0.01) The serum urea nitrogen of the model group was (24.5 +/- 4.9) mmol/L, significantly higher than that of the treatment group [(15.8 +/- 3.9) mmol/L, P<0.05] and that of the sham-operated group (7.4 +/- 0.3 mmol/L, P<0.01). The serum creatinine (P<0.05) of the model group was 88 micromol/L +/- 14 micromol/L, significantly higher than that of the treatment group [(58 +/- 5) micromol/L, P<0.05)] and that of the sham-operated group [(54 +/- 5) micromol/L, P<0.05]. The creatinine clearance rate of the model group was (1.7 +/- 0.7) ml.min(-1).kg(-1), significantly lower than that of the treated group [(3.2 +/- 1.1) ml.min(-1).kg(-1), P<0.05] and that of the sham-operated group [(3.9 +/- 1.5) ml.min(-1).kg(-1), P<0.05]. The glomerular sclerosis index (GSI) in the model group was 41.8 +/- 11.5, significantly higher than that in the sham operation group (2.2 +/- 1.3, P<0.01) and the treatment group (23.4 +/- 6.1, P<0.05). The mean optical density of CTGF mRNA expression in the renal cortex of the model group was a 3 times that of the sham operation group, and the mean optical density of CTGF mRNA expression in the renal cortex of the treatment group was lower by 55.4% compared with that of the model group (P<0.01). The glomerular expressions of TGF-beta1, type IV collagen and fibronectin were significantly up-regulated in the model group in comparison with those in the sham operation group (all P<0.01). The glomerular protein expressions of TGF-beta1, type IV collagen and fibronectin were significantly weaker in the fluvastatin treatment group as compared with the model group (all P<0.01). CONCLUSION: CTGF mRNA expression is markedly upregulated in the renal cortex of 5/6 nephrectomized rats. Fluvastatin suppresses the increased CTGF mRNA expression in renal cortex and ameliorates the glomerular extracellular matrix accumulation.

[Transcranial Doppler monitoring of cerebral blood flow velocity during extracorporeal membrane oxygenation in sheep].

OBJECTIVE: To investigate the hemodynamics during extracorporeal membrane oxygenation (ECMO) and the value of transcranial Doppler (TCD) monitoring. METHODS: ECMO was conducted on 14 sheep. TCD monitoring was conducted at different time-points to examine the bilateral cerebral blood flow velocity (CBFV), including systolic peak flow velocity (Vs), end-diastolic flow velocity (Vd), mean flow velocity (Vm), and pulse index (PI, Vs-Vd/Vm). The general condition, blood pressure, heart rate, and temperature were observed. Two weeks after, the surviving 9 sheep were killed, their brains were taken out and morphological and pathological examinations were done. RESULTS: Anesthesia showed little effect on CBFV. After the ligation of carotid artery and vein, the CBFV pattern only changed slightly, Vs and PI decreased, and Vm and Vd remained almost unchanged. During ECMO with either greater or smaller volume, especially the former, the CBFV pattern showed a non-pulse waves, Vs markedly decreased with a value hardly different from that of Vd, Vs, Vd, and Vm were 62%, 75%, and 69% of the values in normal condition. The pre-ECMO CBFV was not significantly different from those examined any day after ECMO. The differences of pH and PO(2) in femoral artery during different stages were insignificant. PaCO(2) during ECMO with great flow volume and during mechanical ventilation after ECMO was significantly lower than that before ECMO (P < 0.05). The MABP of femoral artery during ECMO with small flow volume was significantly lower than that before ECMO (P < 0.05). Vm was positively correlated with MABP and not correlated with heart rate and temperature. The gross observation of the sheep's brain was normal. Small foci of malacia were seen in the brains of 4 sheep. CONCLUSION: Hemodynamics changes remarkably during ECMO. TCD monitors the CBFV continuously during ECMO, thus helping maintaining the stability of CBFV and protect the brain.