Thalassemia, a genetically inherited hemoglobinopathy, represents a significant global health challenge with profound socioeconomic implications, particularly in endemic regions. The emergence of third-generation sequencing (TGS) technologies has revolutionized thalassemia research and diagnostic paradigms, offering unprecedented capabilities for comprehensive genetic characterization. Between 2021 and 2024, we conducted a comprehensive analysis of 536 clinically suspected thalassemia cases from southern China, conventional diagnostic methods and Nanopore TGS were performed simultaneously. Among the 536 subjects analyzed, TGS identified 332 cases harboring either common or rare variants, which included 160 cases with rare thalassemia variants, 50 cases with abnormal hemoglobin variants, and 122 cases carrying common α- or β-thalassemia mutations. --THAI and HKαα emerging as the most prevalent variants among rare thalassemia, followed by Chinese (Aγδβ)0 and α-Fusion gene. The predominant abnormal hemoglobin was Hb New York (HBB:c.341 T > A). We used TGS and discovered three rare variants that have not been identified by conventional diagnostic methods for thalassemia, the variants included two cases of α-globin chain 32.8 kb deletions and one case of β-globin chain 3.5 kb deletion. Hb G-Ferrara (HBB:c.174 C > A) and Hb Ethiopia (HBA2:c.421 T > C) were firstly identified in the Chinese population. Moreover, two novel α-globin variants: NC_000016.10:g.176260-176930del and HBA1:c.386 T > C were discovered in this study. This study expands the genetic landscape of hemoglobinopathies in Southern China by characterizing a comprehensive spectrum of rare variants. Our findings demonstrate the superior diagnostic capability of TGS in identifying rare thalassemia genotypes, suggesting its potential as a first-line molecular diagnostic tool for comprehensive hemoglobinopathy screening.

Personalized product search (PPS) aims to retrieve products relevant to the given query considering user preferences within their purchase histories. Since large language models (LLM) exhibit impressive potential in content understanding and reasoning, current methods explore to leverage LLM to comprehend the complicated relationships among user, query and product to improve the search performance of PPS. Despite the progress, LLM-based PPS solutions merely take textual contents into consideration, neglecting multimodal contents which play a critical role for product search. Motivated by this, we propose a novel framework, HMPPS, for Harnessing Multimodal large language models (MLLM) to deal with Personalized Product Search based on multimodal contents. Nevertheless, the redundancy and noise in PPS input stand for a great challenge to apply MLLM for PPS, which not only misleads MLLM to generate inaccurate search results but also increases the computation expense of MLLM. To deal with this problem, we additionally design two query-aware refinement modules for HMPPS: 1) a perspective-guided summarization module that generates refined product descriptions around core perspectives relevant to search query, reducing noise and redundancy within textual contents; and 2) a two-stage training paradigm that introduces search query for user history filtering based on multimodal representations, capturing precise user preferences and decreasing the inference cost. Extensive experiments are conducted on four public datasets to demonstrate the effectiveness of HMPPS. Furthermore, HMPPS is deployed on an online search system with billion-level daily active users and achieves an evident gain in A/B testing.

Since the outbreak of COVID-19 in late 2019, the transmission dynamics and clinical presentation patterns of influenza A (Flu A) virus have undergone changes. This article conducted a comparative analysis in clinical characteristics and laboratory results of pediatric patients with Flu A before, during, and after the COVID-19 pandemic. The medical records of 885 children hospitalized with Flu A virus infection at a tertiary hospital in Guangdong Province, China, were retrospectively analyzed. Flu A was confirmed in these cases using a direct immunofluorescence antigen assay. The clinical data for this study span from January 1, 2018, to May 31, 2023. In our study, we observed a total of 340 cases before the COVID-19 pandemic, 196 cases during the pandemic, and 349 cases after the pandemic. Patients after the pandemic had a higher median age on admission (5.66 years, range 3.41–7.70) and exhibited more respiratory symptoms such as cough, sore throat, and nasal stuffiness. The length of hospital stay was longer, and there was a higher percentage of patients with fever duration ≥ 5 days among Flu A patients during the pandemic. Compared to before and during the COVID-19 pandemic, Flu A patients after the pandemic showed significantly reduced white blood cell (WBC) and platelet (PLT) counts (P < 0.001), along with elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in laboratory indexes (P < 0.001). Furthermore, more hospitalized children after the pandemic were diagnosed with benign acute childhood myositis (BACM). Our research results indicates a significant decrease in Flu A cases during the COVID-19 pandemic, and hospitalized children with Flu A have more severe clinical symptoms after the COVID-19 pandemic. These findings have implications for public health policy and clinical management of Flu A cases. Not applicable.

Abstract Background SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children’s medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. Methods We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. Results The median age of patients was 2 years (Interquartile Range, IQR: 1.0–8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5–23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0–14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75–13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. Conclusion We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Objectives: The prevalence of G6PD deficiency has not been reported in Yangjiang, a western city in Guangdong province. This study aims to investigate the molecular characteristics of G6PD deficiency in this region.Methods: Blood samples were collected from adults at a local hospital to screen for G6PD deficiency. The deficient samples were subjected to further analysis using PCR and reverse dot blot to determine the specific G6PD variants.Results: Among the 3314 male subjects, 250 cases of G6PD deficiency were found using the G6PD enzyme quantitative assay, resulting in a prevalence of 7.54% (250/3314) in the Yangjiang region. The prevalence of G6PD deficiency in females was 3.42% (176/5145). Out of the 268 cases of G6PD deficiency tested for G6PD mutations, reverse dot blot identified 20 different G6PD variants. The most common G6PD variant was c.1388G>A (81/268), followed by c.1376G>T (48/268), c.95A>G (32/268), c.1024C>T (9/268), c.392G>T (7/268), and c.871G>A/c.1311C>T (6/268). It was observed that c.871G>A was always linked to the polymorphism of c.1311C>T in this population.Conclusion: This investigation into G6PD deficiency in this area is expected to significantly improve our understanding of the prevalence and molecular characterization of this condition.

ContextThe highly infectious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused large-scale transmission from Dec 2022 to Feb 2023 in China. After this event, a remarkable surge of influenza A (Flu A) occurred from March to May 2023, especially in pediatric patients.ObjectivesThis study aimed to investigate the differences between pediatric patients infected with COVID-19 Omicron and Flu A virus.MethodsA total of 1,063 hospitalized children who admitted into two tertiary general hospital of Guangdong province of China were included. Medical records were compared retrospectively in these patients during the pandemic periods of SARS-CoV-2 omicron and Flu A.ResultsA total of 592 Patients with Flu A were mostly preschool and school-aged (>3y, 76.0%), they showed higher ratio of high fever (≥39°C), cough, rhinorrhea, and vomiting than patients with SARS-CoV-2 omicron. Most of the 471 Omicron patients were young children (0–3y, 74.5%) and had more poor appetite and dyspnea symptom. Benign acute children myositis (BACM) was only observed in patients with Flu A, and a significant male predominance. Multisystem inflammatory syndrome in children (MIS-C) was only found in patients with SARS-CoV-2 Omicron. Compared to the SARS-CoV-2 Omicron group, for both age groups (0–3 years and > 3 years), the Flu A group showed significantly reduced lymphocyte (Lym) counts (P < 0.001), and elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatinine kinase-MB (CK-MB) in laboratory indexes (all P < 0.001). Additionally, it was found that more children hospitalized with COVID-19 had increased C-reactive protein (CRP) levels compared to those with Flu A.ConclusionInfluenza A infections have notably surged in children, coinciding with the relaxation of COVID-19 related social restrictions. During the epidemic periods of Omicron and Flu A virus infection, different clinical and laboratory characteristics were observed in hospitalized children.

Abstract Background It is widely recognized that genetic variation is among the risk factors associated with neonatal jaundice. Therefore, the objective of this study was to assess the impact of genetic variants on Chinese neonates with hyperbilirubinemia. Methods This cohort consisted of 43 cases with normal bilirubin levels, 54 cases categorized as the medium jaundice group (total serum bilirubin less than 342 umol/L), and 33 cases belonging to the high jaundice group (total serum bilirubin exceeding 342 umol/L). Whole exome sequencing was performed on the neonates to identify genetic variations. Results UGT1A1-G71R, mixed feeding and breast feeding were significantly correlated with higher bilirubin value. Homozygous SNP of CAPN12, ECT2L, SLC9B2, PLEKHA4, and hemizygous G6PD were only found in jaundice group but not in control group. Consistent with the result of linear regression, feeding pattern and UGT1A1 G71R were all correlated with level of bilirubin in Fisher exact test (p = 7.81E-13, and p = 2.48E-07, respectively). Conclusion The UGT1A1 gene variants emerged as a prominent risk factor for neonatal jaundice, significantly contributing to elevated bilirubin levels in Chinese neonates, particularly in conjunction with breastfeeding.

Objective We aimed to investigate the clinical findings of hospitalized paediatric COVID-19 patients by the end of 2022.Method All confirmed children with COVID-19 infection admitted into Chaozhou Central Hospital during the COVID-19 outbreak from 19 December 2022 to 1 February 2023 were included. Detailed clinical data of those children were evaluated retrospectively.Results A total of 286 children, ranging in age from 1 month to 13 years old, were diagnosed with SARS-CoV-2 infection. Among these cases, 138 (48.3%) were categorized as mild, 126 (44.0%) as moderate and 22 (7.7%) as severe/critical. Symptoms varied among the children and included fever, upper respiratory tract symptoms, convulsions, sore throat, poor appetite, dyspnoea and gastrointestinal symptoms. Notably, febrile convulsions were observed in 96 (33.6%) patients, while acute laryngitis was documented in 50 (17.5%) cases. Among the severe/critical patients, eight developed multisystem inflammatory syndrome in children (MIS-C), and tragically, one patient’s condition worsened and resulted in death. Furthermore, MRI scans revealed abnormal brain signals in six severe/critical patients. The severe/critical group also exhibited more pronounced laboratory abnormalities, including decreased haemoglobin and elevated ALT, AST, LDH and CK levels.Conclusions Febrile convulsions and acute laryngitis are frequently observed in children diagnosed with SARS-CoV-2 Omicron infection. Moreover, MIS-C and abnormal neuroimaging appear to be relatively common phenomena in severe/critical cases.

Background Human papillomavirus (HPV) is the main cause of cervical cancer. The aim of the present study was to investigate HPV DNA detection and genotyping on paired genital and urine samples and to evaluate if urine samples could be used to monitor HPV infection. Methods Study subjects were recruited from one local hospital in Guangdong of China from September 1, 2011, to June 30, 2012. They were invited to participate if they have taken an HPV genotyping assay for clinical diagnosis of the genital-urinary disease or for a health check-up 3–5 days ago. DNA was extracted from paired genital and urine samples; genotyping was performed with the GenoArray assay. Results A total of 250 patients were recruited, which included 203 females and 47 males. Our results showed that the overall agreement on HPV status between the paired samples was 77.1% (155/201, 95% CI: 0.713–0.829) for females, with a kappa value of 0.523 (95% CI: 0.469–0.632), while the agreement was extremely low in the paired male samples. As to individual genotyping, the greatest agreement was found for HPV16 type-specific identification in females (96.02%, 0.933–0.987), followed by the other 12 high oncogenic risk (HR-HPV) types, while the agreement for low-risk HPV detection is poor (κ < 0.6). Agreement between paired samples showed that HPV detection had a significantly greater concordance in the samples obtained in females than males (p = 0.002). Moreover, the agreement for low-risk HPV detection was significantly lower as compared to HR-HPV detection (48.1% vs. 62.3%, p = 0.044). Conclusion Despite reduced sensitivity, HPV detection in urine closely represents the same trend that is seen with genital sampling. Urine appears to be an appropriate surrogate sample for HPV DNA detection in women with very limited access to healthcare, while the utility of urine for HPV DNA detection in males is less certain.

ObjectiveTo analyze the clinical characteristics of neonatal infection during the outbreak of COVID-19 omicron variant in Guangdong province of China.MethodThe clinical data of neonates infected with COVID-19 omicron variant were collected from three hospitals of Guangdong province, their epidemiological history, clinical manifestation and prognosis were summarized.ResultsFrom December 12, 2022 to January 15, 2023, a total of 52 neonates with COVID-19 infection were identified across three hospitals in Guangdong Province, including 34 males and 18 females. The age of diagnosis was 18.42 & PLUSMN; 6.32 days. 24 cases had clear contact history with adults who were suspected to be infected with COVID-19. The most common clinical manifestation was fever (43/52, 82.7%), the duration of fever was 1-8 days. The other clinical manifestations were cough (27/52, 51.9%), rales (21/52, 40.4%), nasal congestion (10/52, 19.2%), shortness of breath (2/52, 3.8%), and vomiting (4/52, 7.7%). C-reactive protein was only increased in 3 cases. Chest radiological examination was performed in 42 neonates, twenty-three cases showed abnormal chest radiographic findings, including ground-glass opacity and consolidation. Fifty cases were admitted with COVID-19 presentation, two cases were admitted for jaundice. The hospital stay was 6.59 & PLUSMN; 2.77 days. The clinical classification included 3 cases of severe COVID-19 and one critical case. Fifty-one cases were cured and discharged after general treatment, and one critical case with respiratory failure was intubated and transferred to another hospital.ConclusionThe COVID-19 omicron variant infection in neonates is usually mild. The clinical manifestation and laboratory results are not specific, and the short-term prognosis is good.

Objective Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice. Methods The term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations. Results Out of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant ( P < 0.001). Furthermore, the hemoglobin levels in the jaundiced infants with G6PD deficiency (146.85 ± 24.88 g/L) were lower than those without G6PD deficiency (156.30 ± 22.07 g/L) ( P = 0.001). 65 jaundiced infants with G6PD deficiency underwent G6PD mutation testing, and six different genotypes were identified, including c.95A > G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciency Conclusion In newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants.

INTRODUCTION:Neonatal hyperbilirubinemia is common and remains a clinical concern in China. Since neonatal hyperbilirubinemia is linked to genetic factors, we aimed to identify the gene variants of the red blood cell membrane (RBCM) and evaluate the clinical risk factors in Chinese neonates with hyperbilirubinemia.METHODS:117 hyperbilirubinemia neonates (33 cases of moderate hyperbilirubinemia and 84 cases of severe hyperbilirubinemia) and 49 controls with normal bilirubin levels were selected as our study subjects. A customized 22-gene panel with next-generation sequencing (NGS) was designed to characterize genetic variations among the neonates. Sanger sequencing was used to verify the accuracy of the NGS. The clinical risk factors and potential effects of genetic variations in neonates with hyperbilirubinemia were subsequently assessed.RESULTS:After data filtering, suspected pathogenic variants of UGT1A1, SLCCO1B1, and RBCM-associated gene were identified in neonates, the combined numbers of RBCM-associated gene variants were found to have differences between the hyperbilirubinemia group and the controls (p = 0.008), they were also different between severe hyperbilirubinemia and moderate hyperbilirubinemia (p = 0.008), and were correlated with an increased risk of hyperbilirubinemia (odds ratio = 9.644, p = 0.006). The UGT1A1-rs4148323 variant in neonates with hyperbilirubinemia was significantly increased as compared with the controls (p < 0.001). However, there was no statistical difference for the SLCO1B1-rs2306283 variant between the hyperbilirubinemia group and the controls. In addition, breastfeeding contributed to an increased risk of hyperbilirubinemia.CONCLUSION:Our study highlights that the RBCM-related gene variants are an underestimated risk factor, which may play an important role in developing hyperbilirubinemia in Chinese newborns.

ObjectiveThe objective of this study was to analyze the clinical characteristics of pregnant women infected with the COVID-19 omicron variant and their neonates during the outbreak in Guangdong province, China.MethodsThe clinical data of pregnant women infected with the COVID-19 omicron variant and their neonates were retrospectively collected from two hospitals in Guangdong province. Information recorded included age of mother, date of birth, sex, weight at birth, mode of delivery, gestational age, feeding mode, Apgar score, signs, medical records, underlying comorbidities and laboratory results. The presence of SARS-CoV-2 viral RNA was tested using an real-time PCR assay.ResultsSeventy-nine pregnant women infected with COVID-19 omicron variant and their 68 neonates were included in this study. The vast majority (86.1%) of pregnant women was in their third trimester of pregnancy, and only 11 cases (15%) were in the first or second trimester. Of 79 pregnant women, 39 cases were asymptomatic at the time of infection, and 40 mothers presented with mild manifestations of COVID-19. The most common symptoms were fever (92.5%, 37/40) and cough (57.5%, 21/40). All of pregnant women did not receive chest computed tomography (CT) scan or X-ray. No pregnant woman developed severe pneumonia. A total of 68 neonates (3 set of twins) from 65 mothers with COVID-19 were reviewed. Among women who delivered, 34 cases underwent cesarean section, 31 cases underwent vaginal delivery. According to the timing of birth, there were 10 (14.7%) preterm neonates. Two babies were born dead (intrauterine fetal death after 22 weeks of gestation). Of the live babies born (66 cases) from mothers with COVID-19, 9 newborns were lower weight, and one preterm case was born with respiratory distress and intubated, he recovered and developed normally. SARS-CoV-2 nucleic acid testing was conducted on 41 neonates daily after birth, with only one neonate testing positive for SARS-CoV-2 infection on the third day after birth. The infected neonate exhibited typical fever and acute respiratory tract syndrome but ultimately had a good prognosis, recovering after 5 days of treatment.ConclusionAlthough preliminary data suggests the risk of severe maternal and fetal complications from Omicron variant infection during pregnancy is lower than previous variants and Delta variant. Our study, which was conducted on a limited population sample, indicates that there is a possibility of severe complications, such as stillbirth, occurring in some fetal cases. These findings emphasize the need for continued attention from obstetricians.

Even though colon cancer ranks among the leading causes of cancer mortality, early detection dramatically increases survival rates. Many studies have been conducted to determine whether altered metabolite levels may serve as a potential biomarker of cancer that affects key metabolic pathways. The goal of the study was to detect metabolic biomarkers in patients with colon cancer using liquid chromatography-mass spectrometry (LC-MS). This study consisted of 30 patients with colon cancer. An analysis of the metabolomes of cancer samples and para-carcinoma tissues was conducted. We identified a series of important metabolic changes in colon cancer by analyzing metabolites in cancerous tissues compared to their normal counterparts. They are mainly involved in the pentose phosphate pathway, the TCA cycle, glycolysis, galactose metabolism, and butanoate metabolism. As well, we observed dysregulation of AMP, dTMP, fructose, and D-glucose in colon cancer. Additionally, the AUCs for AMP, dTMP, fructose, and D-glucose were greater than 0.7 for the diagnosis of colon cancer. In conclusion, AMP, dTMP, fructose, and D-glucose showed excellent diagnostic performance and could serve as novel disease biomarkers for colon cancer diagnosis.

Background: Thalassemia presents a higher incidence in southern China. The objective of this study is to analyze the genotype distribution of thalassemia in Yangjiang, a western city of Guangdong Province in China. Methods: The genotypes of suspected cases with thalassemia were tested by PCR and reverse dot blot (RDB). Unidentified rare thalassemia genotypes of the samples were further ascertained by PCR and direct DNA sequencing. Results: Among 22467 suspected cases with thalassemia, 7658 cases were found with thalassemia genotypes using our PCR-RDB kit. Among these 7658 cases, 5313 cases were found with α-thalassemia (α-thal) alone, -- SEA /αα was the most common genotype, accounting for 61.75% of α-thal genotypes, and the following mutations were found: α 3.7 /αα, -α 4.2 /αα, α CS α/αα, α WS α/αα, and α QS α/αα. A total of 2032 cases were found with β-thalassemia (β-thal) alone. β CD41-42 /β N , β IVS−II−654 /β N , and β −28 /β N accounted for 80.9% of all β-thal genotypes, and the following genotypes were found: β CD17 /β N , β CD71-72 /β N , and β E /β N . Compound heterozygotes of β-thal and β-thalassemia homozygotes were identified in 11 and five cases, respectively, in this study. α-thal combined with β-thal was identified in 313 cases, showing 57 genotype combinations of the coincidence of both Hb disorders; one extreme patient had a genotype of -- SEA /α WS α and β CD41-42 /β −28 . In addition, four rare α -mutations (-- THAI , HKαα, Hb Q-Thailand, and CD31 AGG>AAG) and six rare β-mutations (CD39 CAG>TAG, IVS-Ⅱ-2 (−T), −90(C>T), Chinese G γ + ( Aγδβ)0 , CD104 (-G), and CD19 A>G) were also found in this study population. Conclusion: This study provided detailed genotypes of thalassemia in Yangjiang of western Guangdong Province in China and reflected the complexity of genotypes in this high-prevalence region, and this would be valuable for diagnosis and counseling for thalassemia in this area.

BACKGROUND:Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin, resulting in sequelaes such as hearing loss, motor and intellectual development disorders, and even death. The pathogenic factors of neonatal hyperbilirubinemia are complex. Different cases of hyperbilirubinemia may have a single or mixed etiology.AIM:To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China.METHODS:Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations.RESULTS:Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China, 32.20% (580/1602) was severe hyperbilirubinemia. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, breast milk jaundice accounted for 12.09%, infection accounted for 10.17%, glucose-6-phosphate dehydrogenase (G6PD) deficiency accounted for 9.14%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 41.72%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6 variant (rs4148323, c.211G>A, p.Arg71Gly), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes.CONCLUSION:The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns, G6PD deficiency and infection. UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus.

OBJECTIVES:Shaokwan is one of the inhabitant regions of Hakka population in Guangdong province of southern China. Previous survey has reported that a higher prevalence of abnormal hemoglobin (Hb) in this region. However, large-scale survey on the molecular characteristics of abnormal hemoglobin in this south-north junctional region has not been reported.In this study, we aim to investigate the molecular characteristics of abnormal hemoglobin in this area.METHODS:Blood samples from medical check-up center in one local hospital were selected for abnormal hemoglobin screening. Hemoglobin electrophoresis and routine blood tests were performed. Hemoglobin variants were further analyzed by PCR and DNA sequencing.RESULTS:Among the 9731 study subjects, 45 cases of hemoglobin variants were found by hemoglobin electrophoresis, which gave an incidence of 0.46% (45/9731) in Shaokwan region. 8 kinds of hemoglobin variants were identified by gene sequencing. Hb Q-Thailand (16/45) was the most common hemoglobin variants, followed by HbE (7/45), Hb NewYork (6/45) and Hb G-Chinese (6/45).DISCUSSION AND CONCLUSION:Hemoglobin variants had obviously genetic polymorphisms in Chinese. Our study of hemoglobin disorders in this special Hakka Chinese population will contribute considerably to our understanding of the historical, emigrational, and genetic relationships among different ethnic group in this region.

BACKGROUND:Neonatal hyperbilirubinemia is a common problem faced by pediatricians. The role of genetic factors in neonatal jaundice has been gradually recognized. This study aims to identify genetic variants that influence the bilirubin level in five patients using next-generation sequencing (NGS).CASE SUMMARY:Five neonates with severe hyperbilirubinemia were retrospectively studied. They exhibited bilirubin encephalopathy, hypothyroidism, ABO blood type incompatibility hemolysis, glucose-6-phosphate dehydrogenase (G6PD) deficiency and premature birth, respectively. A customized 22-gene panel was designed, and NGS was carried out for these neonates. Eight variations (G6PD c.G1388A, HBA2 c.C369G, ABCC2 c.C3825G, UGT1A1 c.G211A, SPTB c.A1729G, EPB41 c.G520A, c.1213-4T>G and c.A1474G) were identified in these five neonates. Genetic mutations of these genes are associated with G6PD deficiency, thalassemia, Dubin-Johnson syndrome, Gilbert syndrome, hereditary spherocytosis, and hereditary elliptocytosis. One of the neonates was found to have compound variants of the EPB41 splice site c.1213-4T>G and c.G520A (p.E174K), but no elliptocyte was seen on his blood smear of 4 years old.CONCLUSION:Pathological factors of severe neonatal hyperbilirubinemia are complicated. Genetic variants may play an important role in an increased risk of neonatal hyperbilirubinemia, and severe jaundice in neonates may be related to a cumulative effect of genetic variants.

Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.

Background:This study aimed to investigate the influence of a variant of the UGT1A1 gene on the occurrence and severity of prolonged jaundice in Chinese infants at term.Methods:175 infants with prolonged jaundice and 149 controls were used in this retrospective case-control study. The infants with prolonged jaundice were subdivided into the mild-medium and severe jaundice groups (TSB ≥ 342 µmol/L). The frequency and genotype distribution of the UGT1A1 and G6PD genes, and clinical parameters including sex, birth weight, delivery mode, gestational age, and feeding mode, were analyzed, and the differences in the parameters between the two groups were compared.Results:The allele frequency of UGT1A1*6 in the prolonged jaundice group was higher than that in the control group. Similarly, it was also higher in the severe jaundice group than in the mild-medium jaundice group. Homozygous and heterozygous UGT1A1*6 were also found more frequently in the prolonged jaundice group than in the control group. Exclusive breastfeeding, homozygous and heterozygous forms of UGT1A1*6 were significant risk indicators for prolonged jaundice. Moreover, UGT1A1*6 was the best predictor of prolonged severe jaundice.Conclusion:UGT1A1*6 appears to be a risk factor for prolonged jaundice with hyperbilirubinemia in term infants of Chinese ancestry who are exclusively breastfed.