Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective: To estimate the diagnostic value of fibronectin type Ⅲ-domain containing protein 5 (FNDC5) in subclinical diabetic cardiomyopathy. Methods: A total of 94 patients with type 2 diabetes (T2DM), who were hospitalized from April 2018 to June 2019 in the Third Affiliated Hospital of Soochow University, were enrolled in this study. Patients were divided into T2DM with cardiac dysfunction (subclinical DCM) group (n=47) and T2DM without cardiac dysfunction (non-DCM) group (n=47) according to echocardiography and gated myocardial perfusion imaging results. Basic clinical data and serum FNDC5 level were compared between the two groups. Logistic regression analysis was used to establish predicting models and the diagnostic efficiency of established models was compared by ROC curve analysis. Results: Compared to non-DCM group, patients in subclinical DCM group were older, with longer duration of diabetes, and had higher levels of glycosylated hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) (all P<0.05). Serum FNDC5 level was significantly lower in subclinical DCM group than in non-DCM group (P<0.001). FNDC5 level was positively correlated with ventricular septal e'(r=0.451,P=0.005), mitral valve e'(r=0.291,P<0.001), the ratio of peak early diastolic trans-mitral flow velocity (E) to peak late diastolic trans-mitral flow velocity (A)(r=0.490,P=0.002), while negatively correlated with A(r=-0.399,P<0.001), the average ratio of E/e'(r=-0.490,P<0.001), tricuspid regurgitation velocity(r=-0.567,P<0.001), left atrial volume index(r=-0.491,P<0.001). Univariate ROC analysis showed that the diagnostic efficacy of FNDC5(AUC=0.940,95%CI 0.897-0.982)was superior to age(AUC=0.639,95%CI 0.523-0.752), diabetic duration(AUC=0.663,95%CI 0.555-0.772), HbA1c(AUC=0.740,95%CI 0.638-0.839), TG(AUC=0.661,95%CI 0.547-0.776), TC(AUC=0.675,95%CI 0.563-0.788)and LDL-C(AUC=0.644,95%CI 0.532-0.756). Model 1 was established with subclinical DCM as dependent variable, age, diabetic duration, TG, TC, LDL-C and HbA1c as independent variables. Model 2 was established by adding FNDC5 as independent variable on the basis of model 1. Diagnostic efficacy for subclinical DCM was compared between the two models by ROC analysis. The diagnostic efficiency was better with model 2 (AUC=0.980) than with model 1 (AUC=0.879, P<0.001). When sensitivity was set at 0.617, the specificity of model 2 was higher than that of model 1(0.979 vs. 0.936). When sensitivity was set at 0.532, the sensitivity of model 2 was higher than that of model 1 (1.000 vs. 0.915). Conclusions: Our findings suggest that serum FNDC5 could be used as a novel biomarker for the diagnosis of subclinical DCM.

The field of two-dimensional (2D) nanomaterial-based cancer immunotherapy combines research from multiple subdisciplines of material science, nano-chemistry, in particular nano-biological interactions, immunology, and medicinal chemistry. Most importantly, the "biological identity" of nanomaterials governed by bio-molecular corona in terms of bimolecular types, relative abundance, and conformation at the nanomaterial surface is now believed to influence blood circulation time, bio-distribution, immune response, cellular uptake, and intracellular trafficking. A better understanding of nano-bio interactions can improve utilization of 2D nano-architectures for cancer immunotherapy and immunotheranostics, allowing them to be adapted or modified to treat other immune dysregulation syndromes including autoimmune diseases or inflammation, infection, tissue regeneration, and transplantation. The manuscript reviews the biological interactions and immunotherapeutic applications of 2D nanomaterials, including understanding their interactions with biological molecules of the immune system, summarizes and prospects the applications of 2D nanomaterials in cancer immunotherapy.

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

OBJECTIVETo analyze the advantages of spatial measurement of anatomical parameters in a 3D model in surgical planning for laparoscopic partial nephrectomy (LPN).

METHODSFrom February, 2016 to October, 2017, 37 patients diagnosed with T1 renal mass underwent LPN based on 3D reconstruction after enhanced CT scanning using the Uromedix-3D system (group A), and another 38 patients received LPN with conventional CT planning (group B). The anatomical parameters were measured in the reconstructed 3D model and the demographic data, surgical outcome and postoperative data were compared between the two groups.

RESULTSIn group A, the average time for 3D model reconstruction was (29.3∓9.7) min; the length, width and depth of the renal defect in 3D model were 3.2∓1.1 cm, 2.6∓0.9 cm and 1.7∓0.7 cm, respectively; The distance of the tumor from the collecting system was 3.8∓2.2 mm; The mean R.E.N.A.L score of the patients was 7∓1.5, and 3 patients had accessory renal artery and 2 had early branching of the renal artery. LPNs were completed via the retroperitoneal approach in all the 75 patients without conversion to open or total nephrectomy. Group A and group B showed significant differences in warm ischemic time (26.7∓6.4 vs 31.9∓7.0 min), tumor-excision time (8.4∓2.6 vs 10.4∓2.8 min), renal defect suture time (18.3∓3.9 vs 21.5∓3.4 min), 24-h volume of retroperitoneal drainage (88.6∓40.2 vs 134.3∓58.3 mL) and 48-h volume of retroperitoneal drainage (127.9∓54.5 vs 198.1∓86.3 mL), but not in the demographic data, operation time, intraoperative blood loss or postoperative hospital stay.

CONCLUSIONS3D reconstruction of the renal masses can be completed efficiently and accurately using this system. Compared with conventional CT-based measurement, 3D spatial measurement of the anatomical structures helps to increase the precision in the performance of LPN and reduce the warm ischemia time.

Objective To observe the clinical effect of etomidate combined with propofol on laparoscopic cholecystectomy.Methods Eight patients undergoing laparoscopic cholecystectomy cho sen from March 2015 to April 2016 in our hospital,falling into ASA Ⅰ or Ⅱ grades,randomly divided into four groups,20 in each.Group A was administered of propofol (2 mg/kg);group B etomidate (0.3 mg/kg);group C etomidate (0.15 mg/kg) combined with propofol (1 mg/kg);group D etomidate (0.1 mg/kg) combined with propofol (1.5 mg/kg).Systolic blood pressure,diastolic blood pressure and heart rate of the four group were compared at the following six time points:before anesthesia induction(T0),1 min before intubation (T1),the intubation moment (T2),1 min after intubation (T3),5 min after intubation (T4),15 min after intubation (T5).The serum of four groups were collected at the time before anesthesia induction (T0),30 min after anesthesia induction (Tb),2 h after induction of anesthesia (Tc) and 24 h after anesthesia induction(Td).Aldosterone,cortisol and adrenocorticotropic hormone in serum were tested by radioimmunoassay.The incidence of adverse reactions such as injection pain and myoclonus during induction,and postoperative nausea and vomiting of the four groups were recorded and compared.Results Compared with T0,HR,SBP at T1,T4 and T5 were significantly decreased in group A (P＜0.05).SBP at T2 were significantly increased in group B (P＜0.05),and SBP at T1 and T5 were significantly decreased in group C (P＜0.05).There was no significant difference of HR at T1,T2,T3,T4 and T5 in group B and C.Compared with T0,HR,SBP at T1,and T5 were significantly decreased in group D (P＜0.05).There was no significant difference in hemodynamics among the four groups.Compared with T0,the levels of Cor and ALD at Tb and Tc were decreased in group B and C (P＜0.05).And the level of ACTH of B and C in Tc were significantly increased (P＜0.05).Compared with group A,the levels of Cor and ALD of group B and C were significantly decreased at Tb and Tc (P＜0.05).Compared with group B,the levels of Cor and ALD of group C and D showed less decrease at Tb and Tc (P＜0.05).And compared with group C,the levels of Cor and ALD of group D showed less decrease at Tb and Tc (P＜0.05).Conclusion Etomidate combined with propofol induced can reduce the side effects induced by propofol or etomidate alone,which is an ideal way of anesthesia induction.

PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.
Animals ; Asthma* ; Bronchoalveolar Lavage Fluid ; Cell Adhesion Molecules ; Chemokines ; Cholesterol ; Cytokines ; Eosinophils ; Epithelial Cells ; Female ; Gene Expression ; Goblet Cells ; HL-60 Cells ; Humans ; Hyperplasia ; Immunoglobulin E ; Inflammation* ; Injections, Intraperitoneal ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Lovastatin* ; Lung ; Mice ; Mucin 5AC ; Mucus* ; Ovalbumin ; Ovum ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the features of intraductal papilloma of the breast in mammography and magnetic resonance imaging (MRI) and assess the diagnostic values of the two imaging modalities.

METHODSFifteen patients with intraductal papilloma of the breast confirmed surgically and pathologically underwent X-ray examination of the breast, and 11 of them also received enhanced MRI. The imaging findings by mammography and MRI were compared.

RESULTSEnhanced MRI clearly displayed the location and morphology of the intraductal papilloma, and 7 patients showed smooth tumor margins and 2 showed irregular margins. On T(1)WI, the lesions were isointense or slightly hypointense, and appeared isointense or slightly hyperintense on T(2)WI. Some of the intraductal papillomas were seen encapsulated in the dilated ductal. The varying enhancement features of the lesions increased the difficulty in distinguishing from carcinoma. Mammography identified intraductal papillomas only in 2 of the 15 cases (13%) with lesion feature similar to that found by MRI. Fine cluster calcification was found in 1 case.

CONCLUSIONMRI can more accurately define the location of the lesion than X-ray. In spite of some resemblance in the MRI findings between intraductal papillomas and breast carcinoma, MRI still serves as a useful diagnostic modality for intraductal papilloma that shows some characteristic findings.

Adult ; Aged ; Breast Neoplasms ; diagnostic imaging ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Mammography ; Middle Aged ; Papilloma, Intraductal ; diagnostic imaging ; pathology ; Sensitivity and Specificity