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

Methods: Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted. Results: Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=–3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=–0.19, p=0.009) as factors independently associated with EOP length (adjusted R²=0.382). Conclusions Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

Objective:To explore the risk factors of colostomy site incisional hernia associated with colorectal can-cer and to construct and validate a nomogram model.Methods:A retrospective case-control study was conducted to collect and analyze the clinical data of patients who underwent stoma reversal after colorectal cancer surgery in the Gen-eral Surgery Department of Linyi People's Hospital from January 2019 to January 2023.A total of 371 patients were en-rolled and divided into SSIH group and non-SSIH group according to whether SSIH occurred.SPSS 25.0 software was used to perform univariate analysis on 22 related factors of patients,and multivariate analysis was performed on statisti-cally significant risk factors to screen out the independent influencing factors of SSIH related to CRC surgery.According to the results of multivariate analysis,the R language version 4.3.1 was used to establish and verify the nomogram risk prediction model.Results:SSIH occurred in 52 of 371 patients(14.02％).The results of univariate analysis showed that BMI,coronary heart disease,incision infection,stoma location,parastomal hernia,and closure time were statistically sig-nificant(P＜0.05).Multivariate analysis showed that coronary heart disease,closure time and parastomal hernia were in-dependent risk factors for SSIH after CRC(P＜0.05).Based on the above results,the nomogram prediction model was successfully drawn and verified.Conclusions:Coronary heart disease,closure time and parastomal hernia are inde-pendent risk factors for SSIH after CRC surgery.The nomogram constructed based on these factors has a high predictive value for SSIH,which can provide a basis for clinicians to prevent and treat SSIH,and help reduce the incidence of SSIH.

BACKGROUND:Early diagnosis of pulmonary fibrosis is the foundation for timely antifibrotic drug therapy.Therefore,exploring and discovering ideal biomarkers that can be effectively used for the early diagnosis of pulmonary fibrosis is crucial for the treatment of the disease.OBJECTIVE:To conduct an in-depth analysis of key autophagy-related genes involved in the process of pulmonary fibrosis by means of bioinformatics and machine learning techniques,in order to investigate whether autophagy-related core genes of pulmonary fibrosis can be used as reliable biomarkers in the assessment of the progression of pulmonary fibrosis.METHODS:Two datasets of pulmonary fibrosis,GSE24206 and GSE110147,were downloaded from the Gene Expression Omnibus(GEO)database(a public database developed and maintained by the U.S.National Center for Biotechnology Information to store and share bioinformatics data),and the gene expression matrices of these two datasets were normalized by using the"limma"package in R software.The autophagy-related genes were extracted from GeneCards database(a database created by the U.S.National Center for Biotechnology Information,which automatically integrates gene-centric data from about 200 Web sources,including genomic,transcriptomic,proteomic,genetic,clinical,and functional information).Differential gene analysis was performed on the pulmonary fibrosis dataset,and the common genes were extracted by cross-comparing the differential genes with the autophagy genes,so as to identify autophagy genes that may play a role in the process of pulmonary fibrosis.The intersecting genes were analyzed for functional enrichment and cellular immune infiltration by gene ontology and Kyoto Encyclopedia of Genes and Genomes.Core genes of pulmonary fibrosis associated with autophagy were screened by protein-protein interactions and machine learning,and core genes were subjected to the enrichment analysis.Diagnostic models were constructed from the identified core genes.Calibration curves were used to assess the predictive ability of the line graph model.An external dataset,GSE21369,was used to perform a receiver operating characteristic curve analysis to validate the expression profiles of pulmonary fibrosis genes associated with autophagy,as well as to predict Chinese herbs associated with the genes IL6 and COL1A2 via the Coremine database.Finally,human embryonic lung fibroblasts were cultured and modelled by transforming growth factor-β1 treatment,and the relative expression of genes in the model cells was verified using qRT-PCR.RESULTS AND CONCLUSION:(1)A total of 51 pulmonary fibrosis differential genes and 25 genes intersecting with autophagy genes were obtained.Gene ontology analysis showed that the 25 intersecting genes were related to extracellular matrix tissue,collagen metabolism,collagen pro-fibroblasts,and growth factor binding,etc.The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that they were mainly related to the Phosphatidylinositol 3-kinase/protein kinase B signaling pathway and the signaling pathway of the extracellular matrix-receptor interactions.(2)Immunoinfiltration analysis revealed that the expression of activated memory CD4+T cells,M0 macrophages,and resting dendritic cells was significantly elevated in the pulmonary fibrosis group(P＜0.05),showing a strong correlation.(3)Two autophagy signature genes involved in the progression of pulmonary fibrosis were identified:COL1A2 and IL6.The column-line diagram model showed that the two core genes predicted the onset of pulmonary fibrosis more accurately,and the receiver operating characteristic curve analysis showed that the two characteristic genes had diagnostic significance.COL1A2 and IL6 were related to the cell-cycle pathway,mitogen-activated protein kinase signaling pathway,Janus kinase-signal transduction and activator of transcription signaling pathway and cytokine-cytokine receptor interactions.A total of 20 Chinese herbs were predicted to be related to COL1A2 and IL6 genes,and their efficacies were mainly to clear away heat and detoxify toxins and to invigorate blood and move qi.COL1A2 and IL6 were verified to be highly expressed in pulmonary fibrosis.To conclude,COL1A2 and IL6 may be potential diagnostic biomarkers for pulmonary fibrosis,but its specificity to pulmonary fibrosis needs to be further investigated.

Suppressor of cytokine signaling 3(SOCS3),a member of SOCS family,plays a major role in cell signaling trans-duction.SOCS3 is important in regulation of immune homeostasis and also involved in the control of energy metabolism,mainly through regulating JAK/STAT pathway.Recent studies have shown that SOCS3 was closely associated with glycolipid metabolic diseases like diabetes and obesity,and can be used as a new target for treatment of these glycolipid metabolic diseases.This review focuses on the latest research progress of the role and mechanism of SOCS3 in glycolipid metabolic diseases,and discusses the possibility of SOCS3 as a therapeutic target for glycolipid metabolic diseases.

Objective To analyze the relationship between the expression of ferroptosis markers in the tumor microenvironment(TME)and the prognosis of transcatheter arterial chemoembolization(TACE)for hepatocellular carcinoma(HCC).Methods This prospective observational study included 100 HCC patients who received TACE treatment at Langfang Hospital of Traditional Chinese Medicine from March 2019 to June 2021 as the study subjects.The levels of 8-isoprostaglandin F2α(8-iso-PGF2α),4-hydroxy-2-nonenal(4-HNE),8-hydroxy-2'deoxyguanosine(8-OH-dG)and hepcidin in plasma were evaluated by ELISA kit at baseline(1 day before TACE),1 day after TACE and 4～8 weeks.The changes of ferroptosis related markers during TACE treatment were compared.The difference between the level of 8-iso-PGF2α,4-HNE and the baseline 1 day after TACE treatment was recorded as △8-iso-PGF2α,△4-HNE.Results Compared with the baseline,the levels of 8-iso-PGF2α and 4-HNE increased significantly and the level of hepcidin decreased significantly one day after TACE treatment,and the differences were statistically significant(t=8.03,16.29,2.92,all P<0.05).Compared with 1 day after treatment,the levels of 8-iso-PGF2α,4-HNE decreased and the level of 8-OH-dG increased at 4～8 weeks after TACE treatment,and the differences were statistically significant(t=9.12,17.17,2.63,all P<0.05).Multivariate COX analysis showed that △8-iso-PGF2α,△4-HNE and 8-iso-PGF2α 1 day after TACE treatment were independent factors affecting the overall survival after TACE(Wald χ2=5.205,13.801,6.054,all P<0.05).The survival time of patients with △4-HNE>2.01 μg/ml was significantly longer than that of patients with △4-HNE≤2.01 μg/ml(Log-rank=5.718,P=0.017),and that of patients with△8-iso-PGF2α>1.75ng/ml was sig-nificantly longer than that of patients with△8-iso-PGF2≤1.75ng/ml(Log-rank=4.163,P=0.041).Conclusion The prognosis of HCC patients who are in a state of high ferroptosis(4-HNE and 8-iso-PGF2 increased)at 1 day after TACE treatment is better,which indicate that ferroptosis mediated HCC death induced by TACE treatment.

Objective:To investigate the independent clinical factors of live birth rate of the first frozen-thawed embryo transfer (FET) cycle after transcervical resection of adhesion (TCRA).Methods:A retrospective case-control study was conducted to analyze the clinical data of patients with intrauterine adhesion (IUA) who received FET in Reproductive Center of Reproductive and Genetic Hospital of CITIC-XIANGYA from January 2019 to June 2022 ( n=6 154). According to the severity of intrauterine adhesions in patients, they were classified into mild adhesions ( n=172), moderate adhesions ( n=5 723), and severe adhesions ( n=259). Based on the FET outcome, the patients were divided into live birth group and non-live birth group. The risk factors and protective factors of live birth were analyzed by multivariate logistic regression. Results:1) No independent factor of live birth was found in the mild IUA group. 2) In the moderate IUA group, the protective factors of live birth included secondary infertility ( OR=1.39, 95% CI: 1.07-1.80, P=0.015), hysteroscopic polypectomy ( OR=1.38, 95% CI: 1.05-1.83, P=0.023), No. of high-quality embryos transferred (one embryo: OR=1.58, 95% CI: 1.37-1.82, P<0.001; two embryos: OR=2.55, 95% CI: 1.80-3.64, P<0.001), two embryos transferred ( OR=1.77, 95% CI: 1.48-2.12, P<0.001), embryo stage (blastocyst transferred, OR=4.93, 95% CI: 3.68-6.63, P<0.001; blastocyst+cleavage transferred OR=1.90, 95% CI: 1.11-3.21, P=0.021), preimplantation genetic testing embryo ( OR=1.42, 95% CI: 1.19-1.69, P<0.001), endometrial thickness before transplantation ( OR=1.11, 95% CI: 1.07-1.15, P<0.001). Risk factors of live birth included female age ( OR=0.94, 95% CI: 0.92-0.96, P<0.001), infertility due to male factor ( OR=0.83, 95% CI: 0.71-0.96, P=0.011), combined repeated implantation failure ( OR=0.60, 95% CI: 0.42-0.87, P=0.007), combined unicornuate uterus/uterus didelphys ( OR=0.25, 95% CI: 0.06-0.79, P=0.033), American Fertility Society score ( OR=0.94, 95% CI: 0.89-0.98, P=0.010), No. of TCRA ( OR=0.83, 95% CI: 0.77-0.90, P<0.001), gonadotropin-releasing hormone agonists down-regulation combined with artificial cycle ( OR=0.56, 95% CI: 0.45-0.69, P<0.001), artificial cycle ( OR=0.62, 95% CI: 0.51-0.76, P<0.001). 3) In the severe IUA group, the risk factor of live birth was artificial cycle ( OR=0.25, 95% CI: 0.07-0.80, P=0.027). Conclusion:The clinical factors that affect the live birth outcome of the first FET cycle after TCRA have different results in patients with different degrees of adhesion. In patients with moderate adhesions, there are 17 clinical indicators that affect the live birth rate. In patients with severe adhesions, the artificial cycle is an independent factor affecting the live birth rate.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.