TAFRO syndrome is a systemic inflammatory disease with unknown etiology.It has low incidence rate and progresses rapidly,which poses a significant challenge for clinicians to make a timely diagnosis and provide reasonable treatment.This article retrospectively analyzed a 65-year-old male patient with iMCD-TAFRO admitted to Minhang Hospital,Fudan University,and visited the Department of Nephrology due to bilateral lower limb edema.The patient exhibited systemic edema,fever,and multiple enlarged lymph nodes.A comprehensive examination showed thrombocytopenia,renal dysfunction,elevated CRP levels,multiple serosal fluid accumulations,and bone marrow reticulin fibrosis.For further diagnosis and treatment,he visited the Hematology Clinic of Zhongshan Hospital,Fudan University.Based on the clinical manifestations,the diagnosis of TAFRO syndrome was considered.After further lymph node pathological consultation,the diagnosis was confirmed as idiopathic multicentric Castleman disease(iMCD)-TAFRO syndrome.Later,the patient was transferred to the hematology department of Minhang Hospital,Fudan University.After 15 days of treatment with methylprednisolone,cyclosporine A,rituximab,and thrombopoietin,there was no significant improvement in the condition.Due to personal reasons,the patient discontinued further treatment and passed away 2 weeks later.

Objective To obtain measurements of fetal four-chamber view and left and right ventricular shapes using two-dimensional speckle tracking,and to explore the clinical quantification of cardiac shape remodeling in small for gestational age(SGA)fetuses.Methods In this study,we prospectively collected data on singleton pregnancies from 28 to 39 weeks that were established in the archives of Obstetrics and Gynecology Hospital,Fudan University from May 2020 to Jul 2021.Fetuses eligible for inclusion criteria were randomly matched according to the ratio of estimated fetal weight(EFW)≥10th percentile(P10)∶EFWP90 in the apical segments of the left ventricle was greater in normal UAPI fetuses than that in low-risk fetuses(24.2%vs.14.3%,P=0.005);the SI of left ventricle in UAPI-normal SGA fetuses was greater in segments S1 to S22 than that of right ventricle with statistically significant difference(all P<0.05),while no significant difference was found between the SI of left and right ventricles in segments S23 and S24.Conclusion About one-fourth of SGA fetuses with normal UAPI have abnormally increased apical segments of the left ventricular SI,suggesting that cardiac remodeling with a predominantly"elongated"apical segments of the left ventricle precedes Doppler anomalies.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Objective To evaluate the application value of four-dimensional CT(4D-CT)in the preoperative localization of primary hyperparathyroidism(PHPT). Methods A retrospective analysis was conducted on the clinical data and parathyroid 4D-CT images of 63 patients who underwent PHPT surgery at Peking Union Medical College Hospital between April 2020 and April 2023.Based on the clinical experience of the hospital's surgeons,parathyroid lesions were categorized into six anatomical regions:around the upper pole of the thyroid,posterior to the mid-thyroid,posterior to the lower pole of the thyroid and the tracheoesophageal groove,below the lower pole of the thyroid and the suprasternal fossa,retrosternal anterior mediastinum,and other rare locations.All images were independently analyzed by two experienced radiologists,with discrepancies resolved through discussion led by a senior radiologist.Using pathological results as the gold standard,the accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),Youden index,positive likelihood ratio(PLR),and negative likelihood ratio(NLR)of preoperative 4D-CT in diagnosing PHPT were calculated. Results There were no statistically significant differences between preoperative 4D-CT and surgical localization in the following regions:around the upper pole of the thyroid(χ²=0.500,P=0.480),posterior to the mid-thyroid(χ²<0.001,P>0.999),posterior to the lower pole of the thyroid and the tracheoesophageal groove(χ²=0.571,P=0.450),below the lower pole of the thyroid and the suprasternal fossa(χ²<0.001,P>0.999),retrosternal anterior mediastinum(χ²<0.001,P>0.999),and other rare locations(χ²<0.001,P>0.999).The preoperative 4D-CT diagnosis of PHPT lesions demonstrated a sensitivity of 82.09%,specificity of 97.43%,PPV of 87.30%,NPV of 96.19%,accuracy of 94.71%,Youden index of 79.52%,PLR of 31.94,and NLR of 0.18. Conclusion Parathyroid 4D-CT demonstrates good diagnostic efficacy in the preoperative localization of PHPT.
Humans ; Hyperparathyroidism, Primary/surgery* ; Retrospective Studies ; Four-Dimensional Computed Tomography ; Male ; Female ; Middle Aged ; Adult ; Aged ; Parathyroid Glands/diagnostic imaging* ; Preoperative Period

OBJECTIVE: To investigate the relationship between peripheral blood T-cell immunoglobulin mucin-3 (TIM-3) and iron overload in patients with myelodysplastic syndrome (MDS) undergoing red blood cell transfusion. METHODS: 120 MDS patients who received treatment at Wuhan Third Hospital from June 2020 to May 2022 were included and analyzed as research subjects, all of whom met the indications for red blood cell transfusion. Blood routine and biochemical indicators were tested before transfusion, and general clinical data of the patients were statistically analyzed. The iron metabolism status of the patients were evaluated. The clinical characteristics of patients with iron overload and the factors affecting iron overload were analyzed. And a correlation analysis was conducted between TIM-3 and other factors affecting iron overload. RESULTS: Among the 120 MDS patients included in this study, 82 cases (68.33%) were detected to have iron overload after red blood cell transfusion. The occurrence time of iron overload was 20-42 weeks, with an average time of 32.35±5.26 weeks, calculated from the first transfusion of red blood cells. The proportion of patients with high-risk and extremely high-risk according to the revised International Prognostic Scoring System (IPSS-R) and WHO classification-based Prognostic Scoring System (WPSS), the volume of blood transfusions, the proportion of transfusion-dependent patients, and the levels of serum hepcidin (Hepc), erythropoietin (EPO), and TIM-3 in patients with iron overload were higher than those in patients with normal iron metabolism, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high-risk and extremely high-risk according to WPSS, blood transfusion volume, transfusion dependence, and upregulation of serum Hepc, EPO, and TIM-3 expression were factors affecting iron overload in MDS patients undergoing red blood cell transfusion (P < 0.05). Pearson correlation analysis showed that serum TIM-3 level in MDS patients were positively correlated with the other factors affecting iron overload (P < 0.05). CONCLUSION Serum TIM-3 is associated with iron overload in MDS patients undergoing red blood cell transfusion, and upregulation of serum TIM-3 expression increases the risk of iron overload after red blood cell transfusion.
Humans ; Myelodysplastic Syndromes/blood* ; Iron Overload/blood* ; Hepatitis A Virus Cellular Receptor 2/blood* ; Erythrocyte Transfusion ; Male ; Female ; Middle Aged ; Aged ; Iron

TAFRO syndrome is a systemic inflammatory disease with unknown etiology.It has low incidence rate and progresses rapidly,which poses a significant challenge for clinicians to make a timely diagnosis and provide reasonable treatment.This article retrospectively analyzed a 65-year-old male patient with iMCD-TAFRO admitted to Minhang Hospital,Fudan University,and visited the Department of Nephrology due to bilateral lower limb edema.The patient exhibited systemic edema,fever,and multiple enlarged lymph nodes.A comprehensive examination showed thrombocytopenia,renal dysfunction,elevated CRP levels,multiple serosal fluid accumulations,and bone marrow reticulin fibrosis.For further diagnosis and treatment,he visited the Hematology Clinic of Zhongshan Hospital,Fudan University.Based on the clinical manifestations,the diagnosis of TAFRO syndrome was considered.After further lymph node pathological consultation,the diagnosis was confirmed as idiopathic multicentric Castleman disease(iMCD)-TAFRO syndrome.Later,the patient was transferred to the hematology department of Minhang Hospital,Fudan University.After 15 days of treatment with methylprednisolone,cyclosporine A,rituximab,and thrombopoietin,there was no significant improvement in the condition.Due to personal reasons,the patient discontinued further treatment and passed away 2 weeks later.

Objective To obtain measurements of fetal four-chamber view and left and right ventricular shapes using two-dimensional speckle tracking,and to explore the clinical quantification of cardiac shape remodeling in small for gestational age(SGA)fetuses.Methods In this study,we prospectively collected data on singleton pregnancies from 28 to 39 weeks that were established in the archives of Obstetrics and Gynecology Hospital,Fudan University from May 2020 to Jul 2021.Fetuses eligible for inclusion criteria were randomly matched according to the ratio of estimated fetal weight(EFW)≥10th percentile(P10)∶EFWP90 in the apical segments of the left ventricle was greater in normal UAPI fetuses than that in low-risk fetuses(24.2%vs.14.3%,P=0.005);the SI of left ventricle in UAPI-normal SGA fetuses was greater in segments S1 to S22 than that of right ventricle with statistically significant difference(all P<0.05),while no significant difference was found between the SI of left and right ventricles in segments S23 and S24.Conclusion About one-fourth of SGA fetuses with normal UAPI have abnormally increased apical segments of the left ventricular SI,suggesting that cardiac remodeling with a predominantly"elongated"apical segments of the left ventricle precedes Doppler anomalies.

Objective To construct reference ranges of cardiac size and morphologic parameters in low-risk fetuses at 28-39 gestational weeks using two-dimensional speckle tracking technique.Methods A prospective collection of 453 low-risk singleton pregnancies with echocardiography at Obstetrics and Gynecology Hospital,Fudan University was used to assess the size(length,width,and area)and morphology(sphericity index,i.e.,the ratio of length to width)of the fetal four-chamber view and two ventricles using two-dimensional speckle tracking technique.Repeated inter-and intra-observer agreement of measurements was assessed using the intraclass correlation coefficients(ICCs).Statistical analysis of cardiac measurement parameters was performed to establish reference ranges of values for cardiac size and morphology in low-risk fetuses.Results The inter-and intra-group ICCs for reproducibility tests of fetal cardiac parameters measurements were 0.691 to 0.980.Fetal four-chamber view and ventricular size increased with gestational week(all P<0.001),the end-diastolic length of the left ventricle was larger than that of the right ventricle,and the end-diastolic diameter was smaller than that of the right ventricle(both P<0.001),while there was no significant difference in the end-diastolic area of the two ventricles(P= 0.050).The spherical index of four-chamber view did not correlate with gestational week(P=0.811).The sphericity index of the basal and intermediate segments of the left ventricle was greater than that of the right ventricle,and the sphericity index of the apical segment was less than that of the right ventricle,the differences were statistically significant(all P<0.01).Conclusion The two-dimensional speckle tracking technique for measuring fetal cardiac parameters has good reproducibility.The reference ranges for cardiac size and morphology in low-risk fetuses developed in this study will be useful for prenatal evaluation of cardiac remodeling.

Objective To investigate the antibacterial effect and its preliminary mechanism of lavender essential oil on multi-drug resistant Acinetobacter baumannii.Methods Micro-dilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)of lavender essential oil against multi-drug resistant Acinetobacter baumannii,and bactericidal kinetic study was employed to determine the onset and maintenance time of lavender essential oil.Meanwhile,the promoting and therapeutic effects of lavender essential oil on wound healing were observed in a mouse model of infection.Subsequently,crystal violet staining was used to determine the inhibition and clearance of multi-drug resistant Acinetobacter baumannii biofilm by lavender essential oil,and laser confocal microscopy was utilized to observe the survival of bacteria in biofilms.NanoDrop instrument was utilized to quantify the leakage of bacterial DNA nucleic acid and protein after intervention with 3 and 6 mg/mL lavender essential oil,and the leakage of bacterial potassium ion was measured by potassium ion test kit.Proteomics technology combined with bio-informatics were applied to explore the action mechanism of lavender essential oil against multi-drug resistant Acinetobacter baumannii.Results The MIC and MBC of lavender essential oil were both 6 mg/mL,which could kill almost all multi-drug resistant Acinetobacter baumannii at the time point of 120 min,and showed an obvious dose-and time-dependent manner.The overall animal model evaluation showed that both 3 and 6 mg/mL lavender essential oil could promote wound healing,and the curative effect was obvious.Further studies confirmed that 3 mg/mL lavender essential oil had a certain biofilm inhibitory effect on multi-drug resistant Acinetobacter baumannii,and 6 mg/mL also had a certain biofilm clearance effect under the same conditions.Meanwhile,when incubated at 37℃ for 1 h,the dose of 3 mg/mL could increase the leakage of DNA nucleic acid and protein,and significantly promote the efflux of potassium ions.Proteomic analysis suggested that the antibacterial effect of lavender essential oil may be related to affecting the oxidorereductase activity and cell metabolic process of multi-drug resistant Acinetobacter baumannii,and interfering with the biosynthesis of cell wall/membrane/envelope and other structures.Conclusion Lavender essential oil at 3 mg/mL can play an antibacterial effect against multi-drug resistant Acinetobacter baumannii,and its mechanism may be related to the destruction of bacterial biofilm and interference with bacterial metabolism.