The Epidemiology and Clinical Features of Deinagkistrodon acutus Envenomation: A Retrospective Study from a Medical Center in Hangzhou, Southeast China.

Deinagkistrodon acutus envenomation is one of the most common types of venomous snakebite in China and causes a series of envenomating effects on its victims. However, more specific information on the characteristics of D. acutus envenomation is rare in the English literature. Therefore, we aimed to give a detailed description of the epidemiological and clinical features of patients with D. acutus envenomation. Patients who were admitted with D. acutus envenomation between January 2018 and December 2021 were enrolled in this retrospective study. The data on demographics, clinical manifestations, laboratory features, management, and outcomes were collected. A total of 158 cases of D. acutus envenomation were enrolled. Men (n = 121; 76.6%) and rural populations (n = 133; 84.2%) were the high-risk groups, and most incidents (n = 141; 89.2%) happened between May and September. The specific effect was tissue necrosis at bite site, which occurred in 72 patients (45.6%). Other envenomation effects include extensive limb swelling, blistering, wound bleeding, and coagulopathy. In the envenomed patients, 155 (98.1%) received antivenom, 47 (29.7%) needed operations, 20 (12.7%) required intensive care, and one died. Deinagkistrodon acutus envenomation is a common snakebites emergency in Hangzhou area. A high rate of tissue necrosis at bite site and venom-induced consumption coagulopathy are the characteristics of D. acutus envenomation. Although the mortality rate is low, some patients still require intensive care.

Development and Validation of a Machine Learning Algorithm to Predict the Risk of Blood Transfusion after Total Hip Replacement in Patients with Femoral Neck Fractures: A Multicenter Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) remains the primary treatment option for femoral neck fractures in elderly patients. This study aims to explore the risk factors associated with allogeneic blood transfusion after surgery and to develop a dynamic prediction model to predict post-operative blood transfusion requirements. This will provide more accurate guidance for perioperative humoral management and rational allocation of medical resources. METHODS: We retrospectively analyzed data from 829 patients who underwent total hip arthroplasty for femoral neck fractures at three third-class hospitals between January 2017 and August 2023. Patient data from one hospital were used for model development, whereas data from the other two hospitals were used for external validation. Logistic regression analysis was used to screen the characteristic subsets related to blood transfusion. Various machine learning algorithms, including logistic regression, SVA (support vector machine), K-NN (k-nearest neighbors), MLP (multilayer perceptron), naive Bayes, decision tree, random forest, and gradient boosting, were used to process the data and construct prediction models. A 10-fold cross-validation algorithm facilitated the comparison of the predictive performance of the models, resulting in the selection of the best-performing model for the development of an open-source computing program. RESULTS: BMI (body mass index), surgical duration, IBL (intraoperative blood loss), anticoagulant history, utilization rate of tranexamic acid, Pre-Hb, and Pre-ALB were included in the model as well as independent risk factors. The average area under curve (AUC) values for each model were as follows: logistic regression (0.98); SVA (0.91); k-NN (0.87) MLP, (0.96); naive Bayes (0.97); decision tree (0.87); random forest (0.96); and gradient boosting (0.97). A web calculator based on the best model is available at: (https://nomo99.shinyapps.io/dynnomapp/). CONCLUSION: Utilizing a computer algorithm, a prediction model with a high discrimination accuracy (AUC > 0.5) was developed. The logistic regression model demonstrated superior differentiation and reliability, thereby successfully passing external validation. The model's strong generalizability and applicability have significant implications for clinicians, aiding in the identification of patients at high risk for postoperative blood transfusion.

Clinical characteristics of snakebite patients attending a tertiary hospital in Hangzhou, southeast China.

BACKGROUND: Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. METHODS: A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. RESULTS: Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. CONCLUSION: Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.

The effectiveness of scalp nerve block on hemodynamic response in craniotomy: a systematic review and meta-analysis of randomized trials.

INTRODUCTION: Strategies that blunt noxious stimuli and stabilize hemodynamics may reduce perioperative cardiovascular complications and enhance recovery after craniotomy. EVIDENCE ACQUISITION: Our systematic literature review and meta-analysis investigated whether scalp nerve block (SNB) reduces the acute hemodynamic response compared with non-SNB (scalp infiltration or control) in adult patients undergoing elective craniotomy. We searched MEDLINE, EMBASE, CENTRAL, and two Chinese databases for randomized trials. Primary outcomes included mean arterial pressure and heart rate during skull pin insertion and surgical incision in craniotomy. Secondary outcomes included incidence of hypertension and dosage of intraoperative analgesic opioids used. Random-effects models were used for meta-analyses. EVIDENCE SYNTHESIS: SNB significantly reduced the mean arterial pressure (mean difference: -14.00 mmHg; 95% confidence interval [CI]: -19.71 to -8.28) and heart rate (mean difference: -11.55 beat/min; 95% CI: -19.31 to -3.80), when compared with non-SNB during skull pin insertion. A similar trend was observed during skin incisions (SNB vs. non-SNB, mean difference in mean arterial pressure: -9.46 mmHg; 95% CI: -14.53 to -4.38; mean difference in heart rate: -9.34 beat/min; 95% CI: -15.40 to -3.28). Subgroup analysis showed that, compared with scalp infiltration, SNB reduced mean arterial pressure and heart during pin insertion but not during skin incisions. SNB also reduced the incidence of intraoperative hypertension, but no difference was observed in intraoperative opioid consumption when compared with non-SNB. CONCLUSIONS: SNB alleviated the craniotomy-associated hemodynamic response. SNB may be superior to scalp infiltration in maintaining hemodynamic stability during pin insertion. However, high-quality trials are still needed to provide more conclusive evidence.

Bacteriological Studies of Venomous Snakebite Wounds in Hangzhou, Southeast China.

Snakebite is a common occurrence in Hangzhou, and identifying bacteria in wounds is very important for snakebite treatment. To define the pattern of wound bacterial flora of venomous snakebites and their susceptibility to common antibiotics, we reviewed the medical charts of patients admitted with snakebite at Hangzhou TCM Hospital from January 2019 to December 2020. A total of 311 patients were enrolled in this study. Among them, bacteria culture was positive in 40 patients, and 80 organisms were isolated. The most frequent pathogens were Morganella morganii and Staphylococcus aureus. According to the results of susceptibility testing, a majority of the isolates were resistant to some common first-line antibiotics, such as ampicillin, ampicillin/sulbactam, amoxicillin/clavulanic acid, cefoxitin, and cephazolin. Quinolones, however, have shown a better antibacterial effect. In conclusion, snakebite wounds involve a wide range of bacteria. Fluoroquinolones, such as levofloxacin and ciprofloxacin, could be an alternative for empirical treatment in patients with snakebite when the effect of other antibiotics is poor.

Vincristine Promotes Transdifferentiation of Fibroblasts Into Myofibroblasts via P38 and ERK Signal Pathways.

Background: Vincristine (VCR) is used in the clinic as an anti-tumor drug. VCR can cause pulmonary fibrosis (PF), leading to respiratory failure. The transformation of fibroblasts into myofibroblasts may play a key role in PF. The present study attempted to reveal the molecular mechanism of VCR-induced PF and the possible involvement of the mitogen-activated protein kinase (MAPK) signaling pathway. Methods: Human embryonic lung fibroblasts (HELFs) were treated with different concentrations of VCR. Inhibitors of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK were added to HELFs. Cell proliferation state was assessed using cell counting kit-8 and by directly counting the number of cells. The expressions of vimentin and α-smooth muscle actin (α-SMA) were investigated using western blot and immunofluorescence analyses. Activation of ERK and P38 was estimated by the expression of phosphorylated p38 MAPK (p-p38), p38 MAPK, phosphorylated ERK1/2 (p-ERK1/2) and ERK1/2 using western blot analysis. Enzyme-linked immunosorbent assay was used to estimate the level of collagen I in cell culture supernatants. Results: Results showed that VCR promoted cellular proliferation, secretion of collagen I and the expression of vimentin and α-SMA. High expression of p-p38 and p-ERK1/2 was associated with the activation of the MAPK signaling pathway. MAPK inhibitors SB203580 and PD98059 suppressed the expression of the above proteins. Conclusion: Our study revealed that VCR could promote the differentiation of fibroblasts into myofibroblasts by regulating the MAPK signal pathway, which may be a promising way to treat VCR-induced PF.

Comparison of 1.0 g/kg of 20% mannitol initiated at different time points and effects on brain relaxation in patients with midline shift undergoing supratentorial tumor resection: a randomized controlled trial.

OBJECTIVE: Previous studies have suggested the use of 1.0 g/kg of 20% mannitol at the time of skin incision during neurosurgery in order to improve brain relaxation. However, the incidence of brain swelling upon dural opening is still high with this dose. In the present study, the authors sought to determine a better timing for mannitol infusion. METHODS: One hundred patients with midline shift who were undergoing elective supratentorial tumor resection were randomly assigned to receive early (immediately after anesthesia induction) or routine (at the time of skin incision) administration of 1.0 g/kg body weight of 20% mannitol. The primary outcome was the 4-point brain relaxation score (BRS) immediately after dural opening (1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). The secondary outcomes included subdural intracranial pressure (ICP) measured immediately before dural opening; serum osmolality and osmole gap (OG) measured immediately before mannitol infusion (T0) and at the time of dural opening (TD); changes in serum electrolytes, lactate, and hemodynamic parameters at T0 and 30, 60, 90, and 120 minutes thereafter; and fluid balance at TD. RESULTS: The time from the start of mannitol administration to dural opening was significantly longer in the early administration group than in the routine administration group (median 66 [IQR 55-75] vs 40 [IQR 38-45] minutes, p < 0.001). The BRS (score 1/2/3/4, n = 14/26/9/1 vs 3/25/18/4, p = 0.001) was better and the subdural ICP (median 5 [IQR 3-6] vs 7 [IQR 5-10] mm Hg, p < 0.001) was significantly lower in the early administration group than in the routine administration group. Serum osmolality and OG increased significantly at TD compared to levels at T0 in both groups (all p < 0.001). Intergroup comparison showed that serum osmolality and OG at TD were significantly higher in the routine administration group (p < 0.001 and = 0.002, respectively). Patients who had received early administration of mannitol had more urine output (p = 0.001) and less positive fluid balance (p < 0.001) at TD. Hemodynamic parameters, serum lactate concentrations, and incidences of electrolyte disturbances were comparable between the two groups. CONCLUSIONS: Prolonging the time interval between the start of mannitol infusion and dural incision from approximately 40 to 66 minutes can improve brain relaxation and decrease subdural ICP in elective supratentorial tumor resection.

A high value of fibrinogen in immunoglobulin A nephropathy patients is associated with a worse renal tubular atrophy/interstitial fibrosis score.

PURPOSE: The purpose of our study was to investigate the relationship between serum fibrinogen value and renal tubular atrophy/interstitial fibrosis in immunoglobulin A nephropathy patients with eGFR ≥90 ml/min/1.73 m2 . PATIENTS AND METHODS: Of 359 patients diagnosed with immunoglobulin A nephropathy after renal biopsy were enrolled in this retrospective study. Demographic, histopathological features, and clinical data were collected. The relationships among these factors were analyzed by using Student's t test, Mann-Whitney U test, Kruskal-Wallis test, Chi-square test, or Fisher's exact test, where appropriate. The logistic regression analysis was performed to examine the independent risk factors. RESULTS: Of 176 immunoglobulin A nephropathy patients with eGFR ≥90 ml/min/1.73 m2 were included in this study, and patients were classified into low fibrinogen (fibrinogen <304.6 mg/dl) and high fibrinogen (fibrinogen ≥304.6 mg/dl) groups, respectively. High fibrinogen groups had advanced age, a higher classification of renal tubular atrophy/interstitial fibrosis, and higher levels of systolic pressure, D-dimer, 24 h urine protein quantitation, nag enzyme. Multivariate logistic analysis showed that fibrinogen (OR = 1.018) was significantly associated with tubular atrophy/interstitial fibrosis. CONCLUSION: Among patients with immunoglobulin A nephropathy, the higher levels of fibrinogen and uric acid may mean a higher score of tubular atrophy/interstitial fibrosis, which suggests the renal biopsy should be performed for these patients as early as possible to defined pathological classification, even though there is no obvious abnormal change in the test of renal function.

Effect of strict intraoperative blood pressure management strategy on postoperative acute kidney injury in non-cardiac surgery: A meta-analysis of randomised controlled trials.

BACKGROUND: Acute kidney injury (AKI) is one of the most serious perioperative complications. 20% to 40% of high-risk patients who undergo non-cardiac surgery have AKI and those with AKI are eight-times more likely to die within 30 days after surgery. It may be related to intraoperative hypotension, which is mainly caused by vasodilatory and cardiodepressant effects of anaesthesia, and/or hypovolemia. Strict intraoperative blood pressure management strategy (strict BP management) is a potential option to prevent postoperative AKI. This strategy refers to additional administration of vasoactive agents under the premise of a protocolised fluid delivery. The efficacy of strict BP management for preventing postoperative AKI in non-cardiac surgery patients was assessed by a meta-analysis. METHODS: We systematically retrieved randomised controlled trials (RCTs) and compared strict BP management with conventional therapy control on effect of postoperative AKI in non-cardiac surgery patients, which were published on PubMed, EMBASE, Cochrane library and Web of Science databases before October 5, 2020. Ultimately, a meta-analysis of all RCTs eligible for inclusion criteria was performed. RESULTS: Five RCTs, comprising 1485 patients, were included in the meta-analysis. Strict BP management was associated with a reduced incidence of postoperative AKI [relative risk (RR) = 0.73, 95% confidence interval (CI): 0.58-0.92, P = .007]. No significant difference was found between strict BP management group and conventional therapy control in mortality at longest follow-up available (RR = 0.92, 95% CI: 0.68-1.25, P = .60). In the subset analysis, the studies using supranormal BP management target was significantly lower in the incidence of postoperative AKI (RR = 0.65, 95% CI: 0.51-0.82, P = .0003) CONCLUSION: Strict BP management is significantly more effective than conventional therapy for the prevention of postoperative AKI. Supranormal target of intraoperative BP management may be considered a more appealing option for the prevention of AKI.

Comparing two airway management strategies for moderately sedated patients undergoing awake craniotomy: A single-blinded randomized controlled trial.

BACKGROUND: In the monitored anesthesia care (MAC) setting for awake craniotomy (AC), maintaining airway patency in sedated patients remains challenging. This randomized controlled trial aimed to compare the validity of the below-epiglottis transnasal tube insertion (the tip of the tube placed between the epiglottis and vocal cords) and the nasopharyngeal airway (simulated by the above-epiglottis transnasal tube with the tip of the tube placed between the epiglottis and the free edge of the soft palate) with respect to maintaining upper airway patency for moderately sedated patients undergoing AC. METHODS: Sixty patients scheduled for elective AC were randomized to receive below-epiglottis (n = 30) or above-epiglottis (n = 30) transnasal tube insertion before surgery. Moderate sedation was maintained in the pre- and post-awake phases. The primary outcome was the upper airway obstruction (UAO) remission rate (relieved obstructions after tube insertion/the total number of obstructions before tube insertion). RESULTS: The UAO remission rate was higher in the below-epiglottis group [100% (12/12) vs 45% (5/11); P = .005]. The tidal volume values monitored through the tube were greater in the below-epiglottis group during the pre-awake phase (P < .001). End-tidal carbon dioxide (EtCO2 ) monitored through the tube was higher in the below-epiglottis group at bone flap removal (P < .001). During the awake phase, patients' ability to speak was not impeded. No patient had serious complications related to the tube. CONCLUSION: The below-epiglottis tube insertion is a more effective method to maintain upper airway patency than the nasopharyngeal airway for moderately sedated patients undergoing AC.

The Prognostic Value of Preoperative Geriatric Nutritional Risk Index in Patients with Pancreatic Ductal Adenocarcinoma.

PURPOSE: Patients with malignancy are more likely to develop nutritional problems. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic index for evaluating nutritional status. The objective of this study was to assess if preoperative GNRI could be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical surgery. PATIENTS AND METHODS: This study included 282 consecutive patients with incident pancreatic ductal adenocarcinoma who were treated with radical surgery. The Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors. A nomogram was developed based on the results of the multivariate analysis, and the predictive accuracy of the nomogram was assessed. RESULTS: Among the 282 patients, there are 117 males and 165 females. The patients had a mean age of 58.7 ±13.5 years, with the median follow-up time of 72.9 months (interquartile range, 0.7 to 115.2 months). They were classified into abnormal (GNRI ≤ 98) and normal (GNRI > 98) GNRI groups, respectively. Multivariate Cox analysis showed that age (HR = 1.023), drinking history (HR = 1.453), tumor grade (HR = 1.633), TNM stage (HR = 1.921), and GNRI (HR = 1.757) were significantly associated with OS. Based on the above variables, the nomogram was established. The concordance index (C-index) and time-dependent receiver operating characteristics curve (tdROC) showed the nomogram was superior to TNM grade and tumor grade in predicting the OS of patients with PDAC. CONCLUSION: GNRI could be a useful prognostic indicator in patients with PDAC who received surgery. Based on the GNRI and the other clinical indicators, we developed a nomogram model that can provide an accurate estimation of OS in patients with PDAC after radical surgery.

Amiodarone induces epithelial-mesenchymal transition in A549 cells via activation of TGF-ß1.

Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal transition (EMT) was a significant process in pulmonary fibrosis. So far, there are no studies about whether EMT was associated with amiodarone-induced pulmonary fibrosis, which was therefore explored in this study. In addition, the underlying mechanisms of amiodarone-induced pulmonary fibrosis were examined in vitro. We found the EMT marker (α-SMA) was significantly increased, while the E-cadherin was significantly decreased in adenocarcinomic human alveolar basal epithelial cells (A549) after amiodarone treatment, suggesting that the epithelial cells were an important source of mesenchymal cells. Transforming growth factor beta1 (TGF-ß1) was also increased significantly after amiodarone treatment. In conclusion, this study suggested amiodarone could induce pulmonary fibrosis via EMT, and the TGF-ß1 may be a key profibrotic cytokine in mechanisms of amiodarone-induced pulmonary fibrosis.

Perioperative acute myocardial infarction in patients after non-cardiac surgery in China: Characteristics and risk factors.

To examine the characteristics and short-term outcome of perioperative myocardial infarction (PMI), a single-center retrospective study was carried out. The electronic medical records of 278,939 patients aged 45 years or older who underwent non-cardiac surgery at Renji Hospital from January 2003 to December 2015 were screened based on diagnostic codes (ICD121, ICD121.0, ICD121.1, ICD121.2, ICD121.3, ICD121.4, or ICD121.9). The incidence and characteristics of PMI and mortality risk factors were analyzed after non-cardiac surgery. PMI was reported in 45 patients, with an incidence rate of 1.61 per 10,000 and a mortality rate of 75.6% (34/45). The PMI incidence rate increased significantly with age. The PMI incidence rate was the highest for vascular surgery (5.82 per 10,000 cases). PMI occurs mainly within 48 h of surgery, with most cases showing an onset in the general wards. Logistic analysis showed that the use of nitrates is the independent protective factor for the outcomes of patients with PMI. The incidence of PMI in non-cardiac surgery is approximately 2 of 10,000 in patients aged 45 years or older, and increased significantly with age. The use of nitrates might be helpful for their survival.

De Novo Germline Mutations in SEMA5A Associated With Infantile Spasms.

Infantile spasm (IS) is an early-onset epileptic encephalopathy that usually presents with hypsarrhythmia on an electroencephalogram with developmental impairment or regression. In this study, whole-exome sequencing was performed to detect potential pathogenic de novo mutations, and finally we identified a novel damaging de novo mutation in SEMA5A and a compound heterozygous mutation in CLTCL1 in three sporadic trios with IS. The expression profiling of SEMA5A in the human brain showed that it was mainly highly expressed in the cerebral cortex, during the early brain development stage (8 to 9 post-conception weeks and 0 to 5 months after birth). In addition, we identified a close protein-protein interaction network between SEMA5A and candidate genes associated with epilepsy, autism spectrum disorder (ASD) or intellectual disability. Gene enrichment and function analysis demonstrated that genes interacting with SEMA5A were significantly enriched in several brain regions across early fetal development, including the cortex, cerebellum, striatum and thalamus (q < 0.05), and were involved in axonal, neuronal and synapse-associated processes. Furthermore, SEMA5A and its interacting genes were associated with ASD, epilepsy syndrome and developmental disorders of mental health. Our results provide insightful information indicating that SEMA5A may contribute to the development of the brain and is associated with IS. However, further genetic studies are still needed to evaluate the role of SEMA5A in IS to definitively establish the role of SEMA5A in this disorder.

Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1/2 and p38 MAPK signaling in fibroblasts.

Amiodarone is a potent antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis. Accumulating evidence has demonstrated that myofibroblast differentiation is related to the pathogenesis of pulmonary fibrosis. In the present study, we treated human embryonic lung fibroblasts (HELFs) with amiodarone, and investigated the relative molecular mechanism of amiodarone-induced pulmonary fibrosis and pathway determinants PD98059 (extracellular signal-regulated kinase (ERK) inhibitor) and SB203580 (p38 mitogen-activated protein kinase (MAPK) inhibitor). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8). The secretion of collagen Ⅰ was detected by ELISA. The expressions of α-smooth muscle actin (α-SMA), vimentin, phosphorylated ERK1/2 (p-ERK1/2), ERK1/2, phosphorylated p38 MAPK (p-p38), and p38 MAPK were investigated using Western blot analysis. The levels of α-SMA and vimentin were also determined by immunofluorescence and qRT-PCR. We report that amiodarone promoted cell proliferation and collagen Ⅰ secretion, induced α-SMA and vimentin protein and mRNA expression accompanied by increased phosphorylation of ERK1/2 and p38 MAPK, and furthermore, PD98059 and SB203580 remarkably reduced the proliferative response of HELFs compared with amiodarone group and greatly attenuated α-SMA, vimentin and collagen Ⅰ protein production induced by amiodarone. Taken together, our study suggests that amiodarone regulates cell proliferation and myofibroblast differentiation in HELFs through modulating ERK1/2 and p38 MAPK pathways, and these signal pathways may therefore represent an attractive treatment modality in amiodarone-induced pulmonary fibrosis.

Signatures of B-cell receptor diversity in B lymphocytes following Epstein-Barr virus transformation.

Epstein-Barr virus (EBV) is a widespread human virus that establishes latent infection, potentially leading to tumors, hematological disorders, and other severe diseases. EBV infections are associated with diverse symptoms and affect various organs; therefore, early diagnosis and treatment are crucial. B cell receptor (BCR) repertoires of B cell surface immunoglobulins have been widely studied for their association with various infectious diseases. However, the specific genetic changes that modulate the BCR repertoires after an EBV infection are still poorly understood. In this study, we employed high-throughput sequencing (HTS) to investigate the diversity of BCR repertoires in an EBV-transformed lymphoblastic cell line (LCL). Compared with the noninfected control B cell line, the LCL exhibited a decrease in overall BCR diversity but displayed an increase in the expansion of some dominant rearrangements such as IGHV4-31/IGHJ4, IGHV4-59/IGHJ4, IGHV5-51/IGHJ3, and IGHV3-74/IGHJ3. A higher frequency of occurrence of these rearrangement types was confirmed in patients with EBV infection. Interestingly, the IGHV3-74 rearrangement was only detected in EBV-infected children, suggesting that our experimental observations were not coincidental. In addition, we identified a highly dominant consensus motif, CAR(xRx)YGSG(xYx)FD, in complementarity-determining region 3 (CDR3) sequences of the heavy chain in the LCL. Our findings demonstrated the utility of HTS technology for studying the variations in signature motifs of the BCR repertoires after EBV infection. We propose that the analysis of BCR repertoire sequences represents a promising method for diagnosing early EBV infections and developing novel antibody- and vaccine-based therapies against such infections.

Differential circRNA expression profiles in latent human cytomegalovirus infection and validation using clinical samples.

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.