ABSTRACT
Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (>100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments. Clinical data were prospectively collected at multiple time points during ICU admission, and amino acid sequences for the NAb CDR3 segments were identified. Patients who survived severe COVID-19 had significantly more of a Class 3 antibody (C135) to SARS-CoV-2 compared to non-survivors (16,315 reads vs 1,412 reads, p=0.02). In addition to highlighting the utility of RNA sequencing in revealing unique NAb profiles in COVID-19 patients with different outcomes, we provided a physical basis for our findings via atomistic modeling combined with molecular dynamics simulations. We established the interactions of the Class 3 NAb C135 with the SARS-CoV-2 spike protein, proposing a mechanistic basis for inhibition via multiple conformations that can effectively prevent ACE2 from binding to the spike protein, despite C135 not directly blocking the ACE2 binding motif. Overall, we demonstrate that deep RNA sequencing combined with structural modeling offers the new potential to identify and understand novel therapeutic(s) NAbs in individuals lacking certain immune responses due to their poor endogenous production. Our results suggest a possible window of opportunity for administration of such NAbs when their full sequence becomes available. A method involving rapid deep RNA sequencing of patients infected with SARS-CoV-2 or its variants at the earliest infection time could help to develop personalized treatments using the identified specific NAbs.
ABSTRACT
ObjectiveTo investigate the genetic polymorphisms of 21 short tandem repeat(STR)loci (D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391 and FGA). Methods A total of 560 blood samples were collected from unrelated healthy individuals of Han population in Hunan Province. Chelex-100 extraction method was applied to the extraction of genomic DNA, and an AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The products were separated and analyzed on 310 Genetic Analyzer.ResultsA total of 248 alleles were observed, the al-lelic frequencies ranging from 0.001 to 0.518. Observation of genotype distributions for each locus showed no deviations from Hardy-Weinberg equilibrium exceptPentaE(P=0.023). The combined pow-er of discrimination, combined power of exclusion, and combined matching probability of the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999 998, and 1.36×10-25, respectively. ConclusionThe 21 STR loci show high polymorphisms in the Han population, which can provide valu-able data and a theoretical basis for forensic individual identification and paternity testing.
ABSTRACT
BACKGROUND:In perioperative period of total knee replacement in elderly patients, it is crucial to maintain the normal function of blood coagulation. However, many factors may influence coagulation function of patients in perioperative period. Of them, anesthesia is an important factor. Different anesthesia methods wil produce different effects on blood coagulation. Appropriate anesthesia methods should be selected in the clinic to maintain the stability of coagulation function. OBJECTIVE:To explore the effect of application of general anesthesia and epidural anesthesia in elderly knee replacement and the effects on the function of blood coagulation. METHODS:A retrospective analysis was performed on clinical data of 135 elderly patients after total knee replacement in Dongying Hospital of Shandong Provincial Hospital Group from September 2012 to September 2013. Al patients were divided into control group (67 cases;general anesthesia) and observation group (68 cases;epidural anesthesia) according to the mode of anesthesia. Coagulation indexes and D-dimer levels were observed before anesthesia, 6 hours after anesthesia, and 1 day after replacement in both groups. The incidence of deep venous thrombosis was measured and compared between the two groups in 12-month fol ow-up. RESULTS AND CONCLUSION:Through the statistics and comparison, no significant difference was detected in blood coagulation indexes at different time points in the two groups (al P>0.05). However, significant differences in D-dimer levels were detectable between the two groups at 6 hours after anesthesia and in the morning at 1 day after replacement. D-dimer levels were significantly lower in the observation group than in the control group (al P<0.05). The incidences of deep venous thrombosis were 3%and 21%in the observation and control groups, respectively, showing significant differences (P<0.05). These results suggest that epidural anesthesia during elderly totak knee replacement obtained good effects, and could maintain stable coagulation function.
ABSTRACT
Objective To assess the clinical efficacy and safety of uniport video-assisted thoracoscopic surgery in treatment of pulmonary bulla.Methods Clinical data of 38 patients with pulmonary bulla treated with uniport video-assisted thoracoscopic surgery were analyzed.Results 30 patients under general anesthesia and double-chamber tracheal intubation anesthesia and 8 patients under general anesthesia and single-chamber tracheal intubation and tracheal plugger anesthesia underwent the resection of their pulmonary bulla through the surgery with uniport video-assisted thoracoscope, and 2 patients therein were simultaneously treated with bilateral resection of pulmonary bulla.36 patients were treated successfully;1 patient was given another exploratory thoracotomy after his unilateral surgery because of progressive hemothorax and substantial pneumothorax;and 1 patient underwent respiratory failure after his unilateral surgery and was improved in respiration 2 days after the help of a respirator.The average time of operations were 52 minutes.It averagely took 3.2 days to remove closed thoracic drainage pipes.The post-operation hospital stays took 6 days.The post-operation follow-up took 7-39 months,without relapse and other compli-cations.No death occurred in this group.Conclusion It is safe and reliable to treat pulmonary bulla by the surgery with uniport video-assisted thoracoscope,which is in line with the concept of minimally invasive surgery and therefore deserves promotion.
