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

With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Aim To investigate the protective effect of Vaccarin(Va)on epithelial-mesenchymal transition(EMT)in renal fibrosis model mice through regulating STAT3,and the underlying mechanism.Methods Left ureter ligation was used to establish a mouse model of unilateral ureteral obstruction(UUO);human kid-ney tubular epithelial(HK2)cells were induced to differentiate by transforming growth factor-β(TGF-β)in vitro.HE and Masson staining were used to observe the morphological changes of renal tissue;kits were used to detect the levels of BUN,Cr,IL-1β and IL-7 in mouse serum;CCK-8 was used to detect the effect of Va on the viability of HK2 cells;RT-PCR was used to detect the levels of inflammatory factors in HK2 cells;Western blot was used to detect the expression of STAT3,p-STAT3,E-cadherin,and α-SMA proteins in renal tissue and HK2 cells;to further investigate the regulation of Va on STAT3,JAK/STAT3 pathway acti-vator RO8191 was used to treat TGF-β-induced HK2 cells,and functional loss was detected.Results Va improved the pathological damage in UUO mice,inhibi-ted the levels of BUN,Cr and inflammatory factors;Va inhibited the phosphorylation of STAT3,upregulated E-cadherin,and downregulated α-SMA protein expres-sion;RO8191 counteracted the inhibitory effect of Va on the phosphorylation of STAT3.Conclusions Va inhibits the phosphorylation of STAT3 and the release of inflammatory factors,improves EMT,thus exerting an anti-renal fibrosis effect.

This study investigated the infection status,drug resistance,and molecular characteristics of Shiga toxin-producing Escherichia coli(STEC)in domestic goats in Chengkou county,Chongqing.In August 2023,283 fecal samples were collected from households in Chengkou county.After enrichment with EC broth and inoculation onto selective media,samples that tested positive for stx1/stx2 were selected for further isolation.The positive strains were investigated with antimicrobial susceptibility testing and whole genome sequencing.According to the whole genomic sequences,the stx subtypes,serotypes,multi-locus sequence types,virulence genes,drug resistance genes,and phylogenetic relationships of the STEC strains were analyzed.Forty-six strains of STEC were isolated from 283 goat fecal samples,thus resulting in a detection rate of 16.25%.The 46 STEC strains were categorized into 12 O∶H serotypes,among which O76∶H19 and O8∶H7 predominated,each represented by 9 strains.Five STEC strains were identified as serotype O157∶H7.The 46 STEC strains were categorized into 11 sequence types(STs),among which ST675 and ST196 predominated,each represented by nine strains,accounting for a 19.57%proportion.The strains were categorized into 7 stx subtypes,among which stx1c(26/46,56.52%),followed by stx2k(9/46,19.57%)predominated.All nine Stx2k-STEC strains were identified as serotype O8∶H7 and sequence type ST196.In antimicrobial susceptibility testing,2 STEC strains were resistant to ampicillin,one strain was resistant to ampicillin/sulbactam,one strain was resistant to cefazolin,and one strain was resistant to cefoxitin.Nine Stx2k-STEC strains were found to carry the beta-lactam resistance gene blaEC-18.Antimicrobial sensitivity tests revealed that the nine Stx2k-STEC strains were sensitive to all 15 tested antibiotics.Moreover,phylogenetic analysis indicated that the 9 Stx2k-STEC strains were remarkably similar but showed high genetic diversity with respect to that of the Stx2k-STEC strains isolated from other regions in China.Goatsare an important animal reservoir for STEC in theChengkou district of Chongqing,and novel sequence type Stx2k-STEC strains distinct from those found in other regions of China were identified in this region.

Aim To investigate the role of corylin in angiotensin Ⅱ(Ang Ⅱ)-induced cardiomyocyte hy-pertrophy and its underlying mechanisms.Methods An Ang Ⅱ-induced cardiomyocyte hypertrophy model was established and treated with corylin.Real-time PCR was employed to assess hypertrophic gene mRNA expression,and immunofluorescence was used to meas-ure cardiomyocyte surface area.Western blot and en-zyme activity assay kits were used to evaluate SIRT1 expression and activity.Results Corylin markedly mitigated Ang Ⅱ-induced hypertrophic gene expression and cardiomyocyte surface area enlargement.Moreo-ver,it prevented the Ang Ⅱ-mediated decline in SIRT1 protein levels and deacetylase activity.Further investi-gation indicated that corylin inhibited Ang Ⅱ-driven NF-κB transcriptional activity and the expression of its downstream target genes,such as TNF-α,IL-6,and IL-1β.Notably,SIRT1 silencing abolished the protective effects of corylin against cardiomyocyte hypertrophy,as well as its regulation of the SIRT1/NF-κB signaling pathway.Conclusion Corylin suppresses cardiomyo-cyte hypertrophy by modulating the SIRT1-dependent NF-κB signaling pathway.

Objective To observe the mid-and long-term effects of Kegel training combined with Pilates training on urinary conti-nence recovery in different body mass index(BMI)male patients with urinary incontinence after prostatectomy.Methods From May,2023 to June,2024,48 patients in Beijing Bo'ai Hospital were recruited and divided into group A(<25 kg/m2,n=15),group B(25 to 30 kg/m2,n=18)and group C(>30 kg/m2,n=15)according to their BMI.All the groups performed Kegel training combined with Pilates training for two months,and followed up at six months from baseline.They were evaluated with one hour pad test,the number of daily urinary incontinence,In-ternational Consultation on Incontinence Questionnaire-Short Form(ICIQ-SF)and modified Oxford Rating Scale before treatment,and four weeks,eight weeks and six months after treatment.Results The intra-group effect,the inter-group effect and interaction effect were significant in the results of one hour pad test and the daily number of urinary incontinence(F>2.955,P<0.05).Post Hoc test showed that they were worse in group C than in groups A and B(P<0.05),and the number of daily urinary incontinence was more in group B than in group A(P<0.05).There was significant difference in the scores of ICIQ-SF and modified Ox-ford Rating Scale among groups in different time points after treatment(Z>10.476,P<0.05)except the score of ICIQ-SF four weeks after treatment(P>0.05),and they were the worst in group C.BMI(group A=1,group B=2,group C=3)was correlated with the results of one hour pad test(r=0.79,P<0.001),the number of daily uri-nary incontinence(r=0.68,P<0.001),and the scores of ICIQ-SF(r=0.68,P<0.001)and modified Oxford Rating Scale(r=-0.47,P=0.001)six months after treatment.Conclusion Kegel training combined with Pilates training could improve the urinary control in patients with urinary in-continence after prostatectomy.The decrease of BMI can promote the recovery of urinary control,and improve the symptoms of later urinary incontinence in mid-and long-term.

Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5％,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.

Objective To develop dynamic prediction models based on multiple postnatal time points to support early diagnosis and individualized intervention for bronchopulmonary dysplasia(BPD)in preterm infants with gestational age<32 weeks.Methods Clinical data of 472 preterm infants with gestational age<32 weeks admitted to the Second Xiangya Hospital of Central South University between January 2016 and November 2020 were retrospectively analyzed.Multivariable logistic regression was applied to develop five independent prediction models at postnatal days 1,7,14,21,and 28.The performance of the models was assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Results Baseline characteristics such as gestational age and birth weight differed significantly between the BPD group(n=147)and the non-BPD group(n=325)(P<0.05).Predictors of BPD evolved across time points:on day 1,key predictors included gestational age,birth weight,Score for Neonatal Acute Physiology II(SNAP-II),invasive mechanical ventilation,and fraction of inspired oxygen>30%;by day 7,additional variables emerged,including fasting duration>2 days,mean feeding advancement rate<8.5 mL/(kg·d),neonatal respiratory distress syndrome,apnea of prematurity,and positive sputum culture;from day 14 onward,nutrition-and treatment-related indicators were incorporated additionally.The models demonstrated good discrimination at postnatal days 1,7,14,21,and 28,with AUCs of 0.917,0.927,0.939,0.944,and 0.968,respectively,and good calibration(Hosmer-Lemeshow P>0.05).Internal validation showed AUCs ranging from 0.899 to 0.958,indicating robust performance.Conclusions Dynamic postnatal prediction models incorporating indicators spanning perinatal factors,respiratory support,nutritional management,and therapeutic interventions demonstrate high predictive performance and facilitate dynamic risk assessment for BPD in preterm infants with gestational age<32 weeks.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

Objective:To explore the neuropathological characteristics of brain tissues from autopsy of patients with schizophrenia.Methods:Forty-two autopsy cases from National Human Brain Bank for Health and Disease, School of Medicine, Zhejiang University from January 2013 to December 2024 were selected as research subjects, among which, 21 were schizophrenia patients(schizophrenia group) and 21 were non-schizophrenia patients (non-schizophrenia group). Clinical data of patients from the two groups were compared. HE staining was used to detect the pathological changes such as infarction, hemorrhage and arteriosclerosis in the brain tissues, silver-nitrate staining was used to detect the amyloid plaques in the brain tissues, Congo red staining was used to detect the pathological changes related to cerebral amyloid angiopathy (CAA) in the brain tissues, modified Gallyas silver staining was used to detect the neurofibrillary tangles in the brain tissues, and immunohistochemical staining was used to detect the expressions of phosphorylated tau protein, β-amyloid protein (Aβ), TAR DNA binding protein 43 (TDP-43), and α-synuclein in the brain tissues. Alzheimer's disease neuropathologic change (ADNC), primary age-related tauopathy (PART), limbic-predominant age-related TDP-43 encephalopathy (LATE), aging-related tau astrogliopathy (ARTAG), Lewy body disease (LBD), and cerebrovascular disease (CVD)-related pathological changes in the brain tissues were evaluated, and differences in positive rates of the above pathological changes were compared.Results:No significant difference in gender, age of death, brain weight, or apolipoprotein E genotype was noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Six schizophrenia patients exhibited low-to-intermediate ADNC, including 4 with low ADNC and 2 with intermediate ADNC. Compared with the non-schizophrenia group, the positive rates of ADNC- and CVD-related pathological changes in the schizophrenia group were significantly higher (0 vs. 28.6%; 9.5% vs. 47.6%, P<0.05). No significant differences in positive rates of PART-, LATE-, ARTAG-, and LBD-related pathological changes were noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Conclusion:Schizophrenia patients show high proportions of ADNC- and CVD-related pathological changes, but relatively low ADNC severity.