Review on Hydroxyurea Usage in Young Children with Sickle Cell Disease: Examining Hemoglobin Induction, Potential Benefits, Responses, Safety, and Effectiveness

Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.

The Prevalence and Clinical Manifestations of Co-Infection in Pediatric Infectious Mononucleosis: A Single-Centered, Retrospective Study

Background: Recent studies indicate that the incidence of infectious mononucleosis (IM) has increased in China. Furthermore, it has been shown that children diagnosed with IM are prone to acquiring other pathogens. However, there is limited research on the prevalence of these co-infections in children with IM. Thus, we conducted this study to determine the prevalence of coinfections and common pathogens, as well as to compare clinical manifestations in children with and without coinfections. Methods: This retrospective observational study was conducted at the Department of Pediatrics Zhongnan Hospital of Wuhan University, Wuhan, China, with data from January 2018 to January 2023. Data, including demographics, symptoms, lab results, and complications, were collected from the hospital’s electronic database and analyzed. The statistical analysis included descriptive statistics, independent samples t-tests and Mann-Whitney tests to compare the means of continuous variables. Statistical significance was determined by p-values less than 0.05. Results: The study involved 216 participants diagnosed with IM, predominantly males (61.6%) aged 0 - 4 years (50.9%). Coinfection was detected in 39.8% of children, with multiple pathogens present in 33.72% of these cases. Among coinfection cases, 40% occurred in children under 5 years old, and females made up 54.2% of these cases. Mycoplasma pneumoniae (MP) was the most prevalent pathogen, accounting for 18.1% of cases. Influenza B (IFB) and Influenza A (IFA) viruses were found in 16.7% and 13.9% of participants, respectively, indicating a notable occurrence of respiratory pathogen coinfections. Male gender, fever, tonsillopharyngitis, lower HGB levels, higher ESR, CRP, and AST levels were correlated with coinfections. Conclusion: In summary, the study revealed a high prevalence of coinfections among children diagnosed with IM, particularly involving Mycoplasma pneumoniae and influenza viruses. These coinfections were notably common in children under 5 years old and were more frequent among females. Clinical manifestations such as fever and tonsillopharyngitis, along with specific laboratory findings including lower hemoglobin levels, elevated ESR, CRP and AST levels, were found to be correlated with coinfections.

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

Clinical significance of MLH1/MSH2 for stage Ⅱ/Ⅲ sporadic colorectal cancer

BACKGROUND The development of colorectal cancer(CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes.In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes(MMR),among which MLH1 and MSH2 are the most important.Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC.We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation.AIM To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage Ⅱ-Ⅲ CRC using immunohistochemical analysis and GeneScan.METHODS Specimens from 681 patients with CRC(395 stage Ⅱ and 286 stage Ⅲ, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested.Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis.RESULTS Five hundred and fifty(80.76%) patients were MLH1/MSH2 positive and 131(19.24%) were negative by immunohistochemistry.MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production(P < 0.05).Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin.MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients(P < 0.001).Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage Ⅱ/Ⅲ CRC.MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio(HR) = 4.064,95%CI: 2.241–7.369].Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage Ⅲ disease(P <0.001, HR = 7.660, 95%CI: 2.974–15.883).However, patients with stage Ⅱ disease or MLH1/MSH2-positive patients with stage Ⅲ disease did not benefit from adjuvant chemotherapy.GeneScan analysis demonstrated that among 133 patients, 105(78.95%) were microsatellite stable, and 28(21.05%) had microsatellite instability(MSI), including 18(13.53%) with high MSI and 10(7.52%) with low MSI.This is consistent with the immunohistochemical results.CONCLUSION MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC.MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage Ⅱ-Ⅲ CRC.

Primary neuroendocrine tumor in the presacral region: A case report

BACKGROUND Primary neuroendocrine tumors (NETs) in the presacral region are extremely rare, some of which are caused by other primary tumors or metastatic rectal carcinoids. Nevertheless, cases of NETs have been increasing in recent years. This report describes the first primary neuroendocrine tumor in the presacral region that was found at our hospital within the last five years. CASE SUMMARY The patient was identified as a 36-year-old woman with a presacral mass and pelvic floor pain. A digital rectal examination revealed a presacral mass with unclear margins and obvious tenderness. Magnetic resonance imaging (MRI) demonstrated a 57 mm × 29 mm presacral lump. An ultrasound-guided needle biopsy confirmed a well-differentiated neuroendocrine tumor. No other primary or metastatic tumors were found. CONCLUSION Comprehensive consideration of our case report and literature reported by others suggests that a conclusive diagnosis of NETs should be based on computed tomography/MRI and pathological examinations. The treatment of primary NETs in the presacral region mainly relies on surgical procedures with follow-up.

Mitochondria-derived small RNAs as diagnostic biomarkers in lung cancer patients through a novel ratio-based expression analysis methodology

Small non-coding RNAs are potential diagnostic biomarkers for lung cancer. Mitochondria-derived small RNA (mtRNA) is a novel regulatory small non-coding RNA that only recently has been identified and cataloged. Currently, there are no reports of studies of mtRNA in human lung cancer. Currently, normalization methods are unstable, and they often fail to identify differentially expressed small non-coding RNAs (sncRNAs). In order to identify reliable biomarkers for lung cancer screening, we used a ratio-based method using mtRNAs newly discovered in human peripheral blood mononuclear cells. In the discovery cohort (AUC = 0.981) and independent validation cohort (AUC = 0.916) the prediction model of eight mtRNA ratios distinguished lung cancer patients from controls. The prediction model will provide reliable biomarkers that will allow blood-based screening to become more feasible and will help make lung cancer diagnosis more accurate in clinical practice.

Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer

Liver cancer presents divergent clinical behaviors.There remain opportunities for molecular markers to improve liver cancer diagnosis and prognosis,especially since tRNA-derived small RNAs(tsRNA)have rarely been studied.In this study,a random forests(RF)diagnostic model was built based upon tsRNA profiling of paired tumor and adjacent normal samples and validated by independent validation(IV).A LASSO model was used to developed a seven-tsRNA-based risk score signature for liver cancer prognosis.Model performance was evaluated by a receiver operating characteristic curve(ROC curve)and Precision-Recall curve(PR curve).The five-tsRNA-based RF diagnosis model had area under the receiver operating characteristic curve(AUROC)88%and area under the precision–recall curve(AUPR)87%in the discovery cohort and 87%and 86%in IV-AUROC and IV-AUPR,respectively.The seven-tsRNA-based prognostic model predicts the overall survival of liver cancer patients(Hazard Ratio 2.02,95%CI 1.36–3.00,P<0.001),independent of standard clinicopathological prognostic factors.Moreover,the model successfully categorizes patients into high-low risk groups.Diagnostic and prognostic modeling can be reliably utilized in the diagnosis of liver cancer and high-low risk classification of patients based upon tsRNA characterization.

Early Diagnostic Value of Circulating MiRNA-21 in Lung Cancer: A Meta-Analysis

To evaluate the early diagnostic value of circulating miRNA-21 in diagnosis of lung cancer, databases such as Wan Fang, VIP, PubMed, and Elsevier were systematically searched from 2005 to 2013 to collect relevant references in which the diagnostic value had been evaluated. The statistics were consolidated and the qualities of the studies were classified. The data were analyzed using Meta Disc1.4 software. The diagnostic value of circulating miRNA-21 in lung cancer was assessed by pooling sensitivity, specificity, the likelihood ratio, and the Summary Receiver Operating Characteristic（SROC） curve. Publication biases of the studies involved were analyzed using Stata 11.0 software. A total of 143 papers were collected of which 8 were included, which contained 600 cases and440 controls. A heterogeneity test proved the existence of homogeneity in this study. Upon analysis using random effects models, the weighted sensitivity was 0.68, the specificity 0.77, the positive likelihood ratio 2.84, the negative likelihood ratio 0.40, and the SROC Area Under the Curve（AUC） was 0.8133. Further analysis by subgroup showed that the 5 indicators mentioned above were 0.72, 0.84, 4.50, 0.27, and 0.8987, respectively, for the serum group and 0.63, 0.70, 1.95, 0.53, and 0.7318, respectively, for the plasma group. We conclude that circulating miRNA-21can be regarded a valuable reference in diagnosis of lung cancer. This research showed that in lung cancer the early diagnostic value of miRNA-21 in serum was better than that in plasma.

The efficacy and safety of NeuroWell antidepressant dietary supplement,Deanxit,and their combination in the treatment of mild-to-moderate depression:A randomized clinical trial

Depression is the leading global cause of,disability,affecting about 300 milion people worldwide.1;2 Depending on the number and severity of symptoms,depressive episodes can be classified as mild,moderate,and severe.Previous studies have typically focused on the treatment of severe refractory depression,while there have been few studies on the treatment of mild-to-moderate depression.