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 assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

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.

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.

Objective To investigate the relationship between serum phenylacetylglutamine(PAGln),short-chain fatty acids(SCFAs)levels and ventricular remodeling and prognosis in patients with chronic heart failure(CHF).Methods A total of 267 CHF patients treated at Jiulongpo District People's Hospital of Chongqing from January 2019 to December 2022 were selected as the CHF group,and 100 healthy individuals underwent physical examination during the same period were selected as the control group.CHF patients were further divided into a poor prognosis group(n=63)and a good prognosis group(n=204)based on 1-year outcomes.Serum levels of PAGln and SCFAs(acetic acid,propionic acid,butyric acid)were measured using liquid chromatography-tandem mass spectrometry.Echocardiography was used to assess ventricular remode-ling indicators including left ventricular mass index(LVMI),interventricular septal thickness in diastole(IVST),left ventricular posterior wall thickness(LVPWT),and left ventricular end-diastolic diameter(LVEDD).Pearson correlation was used to analyze the associations between serum PAGln,SCFAs levels and LVMI,IVST,LVPWT,LVEDD.Multivariate logistic regression was used to identify risk factors for poor prognosis in CHF patients,and receiver operating characteristic(ROC)curves were used to assess the predic-tive value of PAGln and SCFAs levels.Results Serum PAGln levels were significantly higher in the CHF group than in the control group,while acetic acid,propionic acid,and butyric acid levels were significantly low-er(P＜0.05).LVMI,IVST,LVPWT,and LVEDD were significantly elevated in the CHF group compared to the control group(P＜0.05).Serum PAGln levels were positively correlated with LVMI,IVST,LVPWT,and LVEDD(P＜0.05),while SCFAs levels were negatively correlated with these parameters(P＜0.05).Univa-riate analysis showed that age,duration of CHF,NYHA functional classification,atrial fibrillation,LVEF,NT-proBNP,PAGln,acetic acid,propionic acid,and butyric acid were associated with poor prognosis(P＜0.05).Multivariate analysis identified NYHA class Ⅲ-Ⅳ,atrial fibrillation,elevated NT-proBNP,and elevated PA-Gln as independent risk factors for poor prognosis,while higher LVEF and increased levels of acetic acid,pro-pionic acid,and butyric acid were independent protective factors(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)for the combined prediction using PAGln and SCFAs was 0.881,which was greater than that for PAGln(0.800)or SCFAs(0.789)alone(P＜0.05).Conclusion Elevated serum PAGln and decreased SCFAs levels are closely associated with ventricular remodeling and poor prognosis in CHF pa-tients.The combination of serum PAGln and SCFAs levels has a high predictive value for poor prognosis in CHF.

Objective:To analyze the clinical characteristics and outcomes of Haemophilus influenzae (Hi) meningitis in children. Methods:This is a retrospective case series study. This study included 34 Hi meningitis patients who admitted to Beijing Children′s Hospital, Capital Medical University, from January 1, 2010, to December 31, 2023. Data on clinical presentations, laboratory tests, hearing assessment and outcomes at discharge were collected. Patients were divided into 2 groups according to the outcome at discharge: favorable outcome group and unfavorable outcome group. Mann-Whitney U test and Fisher exact test was used to estimate the risk factors for an unfavorable outcome at discharge. Results:Thirty-four patients were enrolled. There were 16 males and 18 females. The age at onset ranged from 3 months to 12 years. Fever (34 patients (100%)), convulsions (17 patients (50%)), and coma (21 patients (62%)) were the common clinical presentations. Twenty-four patients (71%) developed complications. There were 15 patients (44%) needed treatment in the intensive care unit, 5 patients (15%) received intubation, and 4 patients (12%) had developed shock. The favorable outcome group included 23 patients, and the unfavorable outcome group included 11 patients. Female, patients with limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L were risk factors of unfavorable outcome at discharge (all P<0.05). Among the 23 patients (68%) in favorable outcomes group, 13 patients (57%) had data available on their long-term follow-up results, including 12 patients with favorable long-term outcomes and 1 patient with unfavorable long-term outcome. Among the 11 patients (32%) in unfavorable outcomegroup, 1 patient died, the other 10 patients (91%) had data available on their long-term outcomes. Eight patients had unfavorable long-term outcomes and 2 patients with favorable long-term outcomes. Patients who had unfavorable outcomes at discharge were at a greater risk of experiencing unfavorable long-term outcomes ( P=0.001). Conclusions:It is common for patients with Hi meningitis to have intracranial complications or develop into critical conditions. Patients who have limb movement disability, dystonia, ventriculomegaly or hydrocephalus, and who exhibit a concentration of glucose in the initial cerebrospinal fluid lower than 1 mmol/L tend to have unfavorable outcomes; they need to be assessed for sequelae.

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 assess the sound localization ability of patients with unilateral sudden hearing loss during the early period of treatment, to explore its changing characteristics and to analyze influencing factors.Methods:A total of 22 patients with unilateral sudden sensorineural hearing loss, with onset within 3 days, who were hospitalized at Shandong Provincial ENT Hospital between January and April 2024, were collected in this study. The cohort included 13 males and 9 females, with a mean age of 36.5 years. Among them, 10 suffered in the right ear and 12 in the left ear. Additionally, 15 healthy individuals (8 males and 7 females, mean age 29.2 years) were selected as controls. Pure tone audiometry and sound localization tests were reviewed on the first day, third day, fifth day of admission; the third week after onset, and the pure tone average and the root-mean-square error(RMSE) were used as indicators, respectively. The improvement of the ability of sound localization and pure tone average were assessed by correlation analyses using SPSS, version 27.0, and multiple regression analysis was employed to explore effects that might influence sound localization ability.Results:The pure tone threshold and sound localization ability on the third week of onset were improved compared with those on the initial three instances(the first, third, and fifth days of admission). 9 of the 22 patients (40.91%, 9/22) presented normal sound localization ability whereas their hearing loss had not recurred yet. The Spearman correlation analysis revealed a significant positive correlation between the improvement of sound localization ability and hearing improvement ( r=0.57, P<0.001). Meanwhile, multiple regression analysis showed that hearing threshold was a significant factor for sound localization when there was audible frequency. Vice versa, at this circumstance, ages and vertigo were significant factors. Conclusions:For most of the patients with unilateral sudden hearing loss, ability of sound localization improves with the decrease of hearing threshold. Notably, some patients can restore normal levels of sound localization for white noise, even in the presence of hearing loss at certain frequencies, by relying on binaural acoustic cues provided by residual hearing.

Objective: To investigate the effects of "liver-smoothing and spirit-regulating" acupuncture on the intestinal flora, lipopolysaccharide (LPS) and the hippocampal toll-like receptor 4 (TLR4)/ transcription factor (NF)-κB signaling pathway in depressive disorder mouse model, and to explore its underlying mechanisms. Methods: Eighteen male SPF-grade C57BL/6J mice were randomly assigned to the control, model, and acupuncture groups using a random number method, with six mice in each group. The depression disorder model was induced in mice from both the acupuncture and model groups using CUMS. The mice in the acupuncture group were treated with acupuncture at the acupoints of "Baihui" (DU20), "Yintang" (DU29), "Hegu" (LI4), and "Taichong" (LR3) on the 15th day of modeling, with a duration of 20 min per session, once per day, for 2 consecutive weeks. Behavioral differences were assessed using the sucrose preference test, open field test, and forced swim test. Hematoxylin-eosin staining was used to observe pathological changes in the hippocampus and colon. The levels of the inflammatory factors interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and LPS in the hippocampus and colon were measured using Enzyme-linked Immunosorbent Assay. Western blotting was used to detect the expression of TLR4 and NF-κB protein in the hippocampus. Changes in gut microbiota structure and abundance were analyzed by 16 S rDNA sequencing. Results: Compared to the control group, the model group showed reduced sucrose preference rate, time in the center area, and total distance, with an increase in immobility time (P<0.01). Inflammatory pathological changes were observed in the hippocampal CA1 region and colon. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon increased (P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were increased (P<0.01). The Chao1 index was increased (P<0.01). The relative abundances of Pseudomonadales, Acinetobacter, Moraxellaceae, Solibacillus, Escherichia_shigella, Enterobacteriaceae, Enterobacterales, Dubosiella, and Erysipelottichales were decreased, while the relative abundances of Alloprevotella and gram_negative_bacteriurh_cTPY_13 were increased (P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were upregulated, and the pathway of terpenoid backbone biosynthesis was downregulated (P<0.01). Compared to the model group, the acupuncture group showed increased sucrose preference, time in the center area, and total distance, with a decrease in immobility time (P<0.01). The inflammatory pathological changes in the hippocampal CA1 region and colon were alleviated. The contents of IL-1β, IL-6, TNF-α, and LPS in the hippocampus and colon were reduced(P<0.01). The protein expression levels of hippocampal TLR4 and NF-κB were reduced (P<0.01). The Chao1 index was decreased (P<0.05), and the relative abundances of Dubosiella and Erysipelotrichaceae were increased, while the relative abundance of Rikenellaceae, Alloprevotella, and gram_negative_bacteriuch_cTPY_13 were decreased(P<0.05). The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were significantly downregulated, and the pathway of terpenoid backbone biosynthesis was upregulated (P<0.01). Conclusion " Liver-smoothing and spirit-regulating" acupuncture can improve depressive symptoms in depressive disorder mice, potentially through regulating the LPS and TLR4/NF-κB signaling pathway mediated by intestinal flora, reducing the inflammatory response of the hippocampus, and improving the pathological injury of the hippocampus.