OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

To analyze the clinical and genetic features of oculopharyngodistal myopathy (OPDM) patients and compare the phenotypic differences among various causative genes.

Extracellular vesicles(EVs)are nanoscale membrane vesicles released by cells that carry bioactive molecules such as proteins and nucleic acids. They play a key role in intercellular communication. In recent years, they have shown significant potential in the diagnosis and treatment of corneal and ocular surface diseases. As diagnostic biomarkers, EVs derived from tears or other sources can reflect disease-specific characteristics, providing a basis for the early disease detection. In terms of therapy, mesenchymal stem cells(MSCs)-derived EVs deliver miRNAs to modulate inflammatory pathways, promote corneal epithelial repair, and inhibit fibrosis. Furthermore, as natural drug vehicles, EVs enable precise delivery of therapeutic agents and promote corneal wound healing. This review systematically summarizes the recent research advances in the application of EVs in the field.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.

Objective:To investigate the diagnosis，therapeutic strategy and early prognosis of Scimitar syndrome in pediatric patients.Methods:Clinical data of 21 children with Scimitar syndrome admitted to the Department of Cardiothoracic Surgery of Shanghai Children's Medical Center from January 2014 to December 2021 were retrospectively analyzed，and divided into 11 cases in the infantile-type group and 10 cases in the adult-type group.Results:Twenty-one children with Scimitar syndrome，10 males and 11 females，aged 5 days to 10 years old. Compared with the adult-type group，the infant-type group had a high proportion of preoperative clinical symptoms( P<0.05)，a high concomitant rate of intracardiac malformations (100% vs. 40%， P=0.002)，a big size of aortopulmonary collateral(APC)[(0.77±0.25) mm/kg vs.(0.36±0.13) mm/kg， P=0.016]，a high incidence of pulmonary hypertension(91.0% vs. 50.0%， P=0.038), and a high proportion of severe pulmonary hypertension(50 % vs. 0). There was a high rate of postoperative complications of low cardiac output syndrome (36.4% vs. 0， P=0.034)，prolonged postoperative mechanical ventilation [(73.22±44.75) h vs. (19.5±12.79) h， P=0.007]，and prolonged length of ICU stay[(7.89±3.37) d vs. (2.50±1.26) d， P<0.001]. Eleven cases underwent surgical treatment only，and 10 cases received hybrid operation with APC occlusion. The survival rate of the whole group was 90.5%，and there was no case of pulmonary venous obstruction in the early postoperative period. Systolic pulmonary artery pressure/systolic artery pressure decreased significantly after surgery in 15 children with pulmonary arterial hypertension( P<0.01).Five cases in the infantile-type group still had pulmonary hypertension. Conclusion:Surgical effect of Scimitar syndrome in pediatric patients is satisfactory. Infants with Scimitar syndrome usually have more severe symptoms, higher incidence of severe pulmonary hypertension and relatively longer postoperative recovery time.

Objective:To investigate the clinicopathological characteristics and prognostic factors of biliary neuroendocrine neoplasms (NENs).Methods:The retrospective cohort study was conducted. The clinicopathological data of 36 patients who underwent surgical treatment for biliary NENs at The First Hospital of Jilin University from January 2013 to December 2023 were collected. There were 22 males and 14 females, aged (59±9)years. Observation indicators: (1) clinicopatholo-gical characteristics of patients; (2) follow-up; (3) prognostic factors analysis of patients. Compari-son of measurement data with normal distribution among multiple groups was conducted using the ANOVA. Comparison of measurement data with skewed distribution among multiple groups was conducted using the Kruskal-Wallis H test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. The Cox risk regression model was used for univariate and multivariate analyses. Results:(1) Clinicopatholo-gical characteristics of patients. None of the 36 patients with biliary NENs had carcinoid syndrome. There were 11 cases with tumor located at gallbladder, 14 cases with tumor located at bile duct, and 11 cases with tumor located at ampulla of Vater. There were significant differences in weight loss and TNM stage among biliary NENs patients with different tumor location ( χ2=9.14, 6.54, P<0.05). Of the 36 patients, there were 12 cases with neuroendocrine tumors, 16 cases with neuroendocrine carcinomas, and 8 cases with mixed neuroendocrine-non-neuroendocrine neoplasms. (2) Follow-up. All 36 patients were followed up for 39(range, 10-93)months. Of the 36 patients, 19 patients experienced tumor recurrence and 16 patients experienced tumor metastasis. There were 18 patients died. The median overall survival time of 36 patients was 30 months, with the 1-, 2-, 3-year overall survival rates of 63.9%, 51.0%, and 35.7%, respectively. The 1-, 2-, 3-year recurrence-free survival rates were 47.5%, 34.1% and 21.3%, respectively. The 1-, 2-, 3-year overall survival rates of 19 patients with tumor recurrence were 55.6%, 55.6% and 27.8%, respectively. The 1-, 2-, 3-year overall survival rates of 17 patients without tumor recurrence were 71.3%, 50.4% and 42.0%, respectively. There was no significant difference in overall survival between patients with and without tumor recurrence ( χ2=0.24, P>0.05). (3) Prognostic factors analysis of patients. Results of multivariate analysis showed that pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin were independent risk factors influencing overall survival time of patients ( hazard ratio=5.50, 5.33, 14.04, 95% confidence interval as 1.32-23.01, 1.17-24.35, 2.67-73.79, P<0.05). Conclusions:Biliary NENs lack specific clinical manifestations. Poorly differentiated neuroendocrine carcinomas are the most common pathological type. Pathological type as neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasms, non-R 0 margin are independent risk factors influencing prognosis of patients.

Objective To analyze the clinical characteristics of drug-induced liver injury(DILI)caused by different drug categories,and to investigate factors influencing DILI prognosis.Methods Medical records of DILI patients diagnosed in our hospital from January 1,2019 to December 31,2023 were retrospectively collected.Clinical characteristics of DILI induced by different drug categories were analyzed.Multivariate Logistic regression was employed to identify prognostic factors of DILI.Results A total of 347 DILI patients were included.The predominant DILI pattern was hepatocellular injury(67.15％),followed by cholestatic(20.46％)and mixed types(12.39％).The top three causative drug categories were traditional Chinese medicine(25.34％),antineoplastic drugs(24.15％)and anti-infective agents(21.26％).Regarding prognosis outcomes,7 cases(2.02％)achieved complete recovery,269 cases(77.52％)showed improvement,and 71 cases(20.46％)demonstrated no improvement.Significant differences were observed among prognosis groups in age,gender,alanine aminotransferase level,aspartate transaminase level,alkaline phosphatase levels,DILI patterns,number of combined hepatoprotective drugs used,and causative drug categories(P＜0.05).Multivariate analysis revealed that cholestatic type[OR=0.237,95％CI(0.083,0.673),P=0.007]and combination therapy with＞2 hepatoprotective drugs[OR=0.551,95％CI(0.295,0.998),P=0.018]were independent risk factors for prognosis.Conclusion The number of hepatoprotective drugs used in combination and DILI patterns may serve as potential indicators for prognosis evaluation.Particular attention should be paid to the hepatotoxicity of traditional Chinese medicine,antineoplastic agents,and anti-infective drugs.Rational drug selection is essential for improving DILI prevention and treatment.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.

Background and Aims:Tumor deposits(TDs)may influence prognosis beyond the current 8th edition AJCC pTNM nodal classification in gastric cancer(GC).This study investigates the prognostic value of TD number and proposes an improved pN staging(mpN)that classifies patients with TD number>1 as pN3b.We validated the mpN staging against the 8th AJCC pN staging.Methods:A dual-center retrospective cohort study was performed,including 1 327 patients who underwent radical gastrectomy at Sun Yat-sen University Cancer Center(2011-2015;test cohort)and 340 patients from Guangdong Provincial People's Hospital(2015-2022;validation cohort).Patients were dichotomized into low-TD(≤1)and high-TD(>1)groups.Outcomes were overall survival(OS)and disease-free survival(DFS).Survival analyses used Kaplan-Meier curves,IPTW,and Cox regression.Predictive performance of staging systems was assessed by time-dependent ROC(tROC)/tAUC,concordance index(C-index)and Akaike information criterion(AIC).Results:TDs were present in 435/1 327(32.7%)in the test cohort.Presence of TD was associated with worse OS(IPTW-adjusted HR=2.69,95%CI=2.18-3.31,P<0.01)and DFS(HR=2.82,95%CI=2.32-3.42,P<0.01).In multivariable models,TD remained an independent adverse factor for OS(HR=1.65,95%CI=1.34-2.05;P<0.01)and DFS(HR=1.74,95%CI=1.43-2.11,P<0.01).Increasing TD number correlated with progressively poorer survival;X-tile identified>1 as an optimal cutoff,with high-TD patients showing markedly worse outcomes(OS:adjusted HR=3.65,95%CI=2.74-4.88;DFS:adjusted HR=3.74,95%CI=2.85-4.91;both P<0.01).Incorporation of TD number into the mpN staging(assigning TD>1 to pN3b)improved prognostic discrimination:in the test cohort 5-year OS tAUC was 0.746 for mpN vs.0.703 for AJCC pN(C-index 0.738 vs.0.721,AIC 5 805.27 vs.5 849.30);similar improvements were observed in the validation cohort.Conclusion:TD presence and number exert significant negative prognostic impact in GC.Classifying patients with TD number>1 as pN3b enhances prognostic accuracy.Routine reporting of TD counts and further prospective multicenter validation of mpN staging are warranted.