OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective To investigate whether dexmedetomidine(DEX)can inhibit the inflammatory response mediated by microglia after traumatic brain injury(TBI)in rats through the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods A TBI rat model was constructed,and successfully modeled rats were randomly separated into TBI group,low and high-dose dexmedetomidine treatment groups(DEX-L,DEX-H groups),and high-dose dexmedetomidine treatment+cGAS-STING pathway activator group(DEX-H+DMXAA group),with 18 rats in each group.Additionally,18 healthy normal rats were selected as the Control group.Rats in each group were subjected to neurobehavioral scoring(mNSS).The brain water content of rats in each group was detected.Flow cytometry was used to detect Tregs in the brain tissue of each group.ELISA was applied to detect the levels of inflammatory cytokines in brain tissue.HE staining was applied to observe brain tissue injury.TUNEL staining was applied to detect neuronal apoptosis.Immunohistochemistry was applied to detect the expression of the microglial cell marker ion calcium binding adapter molecule 1(Iba1).Western blot was applied to detect the expression of apoptosis and cGAS-STING pathway related proteins.Results Compared with the Control group,the TBI group showed structural injury to brain tissue,edema,abnormal neuronal morphology,reduced number and disordered arrangement,deep staining of nuclear folds,and blurred nucleoli,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1 β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Compared with the TBI group,the brain tissue structure of the DEX-L and DEX-H groups was slightly injuried,edema was reduced,and the morphology of neurons was relatively normal,with a small decrease in number and relatively neat arrangement,a small amount of nuclei were wrinkled and deeply stained,and most of the nucleoli were obvious,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were reduced(P＜0.05).The brain tissue structure and neuronal injury in the DEX-H+DMXAA group were more severe than the DEX-H group,the mNSS score,brain tissue water content,levels of Tregs,TNF-α,IL-1β,IL-6,neuronal apoptosis rate,expression of caspase-3,caspase-3,Iba1,cGAS,p-STING,p-TBK1,p-IRF3,IFN-Ⅰ were elevated(P＜0.05).Conclusion Dexmedetomidine can inhibit the inflammatory response mediated by microglia after TBI in rats,and its mechanism of action is related to the inhibition of the cGAS-STING pathway.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.

Objective:To investigate a novel coating technology for artificial blood vessel pipelines, conducting preliminary tests on the mechanical stability, hemocompatibility, and biocompatibility of the coating.Methods:The polyester braided artificial blood vessels produced by Terumo Corporation were subjected to three different experimental treatments and divided into three groups. Model group: The uncoated artificial blood vessels were thoroughly cleaned and freeze-dried. Experimental group: The artificial blood vessels were first immersed in a dopamine solution to form a polydopamine(PDA) coating on their surface, and then further immersed in an earthworm active protein/gelatin(EWAP/GT) solution to create PDA/GT/EWAP-modified artificial blood vessels. Collagen group: The untreated polyester woven artificial blood vessels served as the control. The study detailed the characterization, porosity, water permeability, degradation rate, blood compatibility, and cytotoxicity of the PDA/GT/EWAP-coated artificial blood vessels. Additionally, a 2-week in vivo study was conducted to evaluate the biocompatibility of the PDA/GT/EWAP-coated artificial blood vessels implanted subcutaneously in SD rats.Results:The PDA/GT/EWAP-coated artificial vascular grafts were successfully fabricated. The artificial blood vessels in the PDA/GT/EWAP group exhibited a porosityof(50.53±1.10)%, with water permeability showing a gradual decreasing trend over time. The overall in vitro degradation rate at 4 weeks was(1.83±0.08)%, and the PDA/GT/EWAP group demonstrated favorable mechanical stability. The activated partial thromboplastin time(APTT) of the PDA/GT/EWAP group was(26.30±0.46)s, the thrombin time(TT) was(18.83±0.49)s, the hemolysis rate was(2.15±0.09)%, and the plasma recalcification time(PRT) was(191.00±10.54)s, indicating excellent blood compatibility and anticoagulant properties. MTT assay evaluation of the PDA/GT/EWAP group revealed no significant cytotoxicity. After subcutaneous implantation of vascular samples in rats for 2 weeks, analysis of blood immune parameters and hematoxylin-eosin(HE) staining of the artificial vascular samples showed that the immune response in the PDA/GT/EWAP group exhibited no significant difference compared to the collagen group and was superior to the model group. Conclusion.Conclusion:The PDA/GT/EWAP composite-coated artificial blood vessel demonstrates excellent mechanical properties, good hemocompatibility, biocompatibility, and low cytotoxicity. It also shows remarkable stability. This research offers a new approach for domestic technological breakthroughs in related fields.

Objective To explore the efficacy of a compound nutrition preparation on wound healing after acute trauma and investigate the underlying mechanism primarily.Methods After skin wound model was successfully constructed on totally 60 male SD rats surgically,they were randomly divided into control group(CON group),whey protein group(WP group)and low-and high-dose nutritional formula groups(LDF and HDF groups),with 15 animals in per group.From the next day after surgery,the rats in each group were given corresponding nutritional interventions for 2 weeks.During the intervention,the wound conditions were observed and recorded,and the wound area was measured.The samples were collected on the 3rd,7th and 14th days after surgery,respectively.Serum albumin(ALB),prealbumin(PA),total protein(TP),inflammatory factors(TNF-α,IL-1β,IL-6 and IL-10),immunoglobulins(IgA,IgG and IgM)and hydroxyproline(Hyp)were detected by the corresponding reagent kits.The histopathologic changes of wound were observed with HE staining.Masson staining was used to observe the collagen fiber deposition in wound tissue.The angiogenesis of wound tissue was evaluated by immunohistochemical staining.Results Compared with the CON group,the wound healing speed,collagen synthesis and angiogenesis speed were significantly accelerated in the WP group,LDF group and HDF group(P＜0.05),and the effects were the most obvious in the HDF group.On the 3rd day after surgery,in the WP,LDF and HDF groups,the serum ALB,PA and TP levels were significantly increased(P＜0.05),serum TNF-α and IL-1β levels were obviously decreased(P＜0.05),and serum IL-10 level was notably increased(except WP group)when compared with the CON group.The serum IgG and IgM levels were significantly increased in the LDF group and HDF group(P＜0.05)and significant increment of IgA was only observed in the HDF group(P＜0.05).On the 7th day after modeling,the levels of ALB,PA and TP were significantly increased(P＜0.05),the levels of TNF-α,IL-1β and IL-6 were obviously decreased(P＜0.05),and the levels of IL-10 were remarkably increased(P＜0.05)in the HDF group than the CON group;The LDF group and HDF group had significantly elevated serum IgG and IgM levels(P＜0.05),but only the former group had statistically increased serum IgA level(P＜0.05).On the 14th day after modeling,the HDF group had significantly increased levels of ALB and TP(P＜0.05),decreased levels of IL-1β(P＜0.05),and raised levels of IgG and IgM when compared with the CON group(P＜0.05).Conclusion Our compound nutrition preparation promotes wound healing in rat model of acute trauma,which might be related to its improving the nutritional status,promoting collagen synthesis,and thus alleviating inflammatory response and enhancing immune function.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.