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

Residual inflammatory risk （RIR） is a key issue to be urgently addressed in the secondary prevention of atherosclerotic cardiovascular disease （ASCVD）. Targeted intervention of RIR has become a novel target for drug development and clinical management. A series of high-quality randomized controlled trials （RCTs）， including COLCOT， LoDoCo2 and CLEAR SYNERGY， provided high-level evidence and confirmed that low-dose colchicine （0.5 mg/d） significantly reduced the risk of cardiovascular events in ASCVD patients at stable stage or after the acute phase， while its efficacy varied in different clinical scenarios. International authoritative guidelines from the European Society of Cardiology and the American Heart Association/American College of Cardiology include low-dose colchicine in the recommendations for ASCVD secondary prevention. Two domestic guidelines released in 2024， namely the Guideline for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndrome （ 2024 ） and the Guideline for the Diagnosis and Management of Chronic Coronary Syndrome in China ， have also added relevant recommendations. Nevertheless， due to potential racial differences， safety concerns regarding drug-drug interactions， and the relative lack of clinical evidence in China， especially the absence of prospective RCTs using low-dose colchicine for secondary prevention of ASCVD patients， current clinical recommendations still mainly based on international evidence and guidelines， and should not be simply extrapolated.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objective To investigate the relationship between serum microRNA(miRNA,miR)-9-5p,miR-21-5p and miR-206 and hemorrhagic transformation(HT)occurs and prognosis in patients with large ar-tery atherosclerotic cerebral infarction(ACI-LAA)after thrombolysis.Methods A total of 265 patients with ACI-LAA admitted to the hospital from April 2021 to November 2023 were selected as the research objects.According to whether HT occurred after intravenous thrombolysis,they were divided into non-HT group and HT group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.The general data of patients with ACI-LAA were collected.Univariate and multivariate Logistic regression analysis were used to analyze the influencing factors of HT occurs in patients with ACI-LAA after thrombolysis.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting HT occurs after thrombolysis in patients with ACI-LAA.The patients with ACI-LAA were followed up for 90 d.According to the modified Rankin scale(mRS)score,the patients were divided into a good prognosis group and a poor prognosis group,and the expression levels of serum miR-9-5p,miR-21-5p and miR-206 were compared between the two groups.Univa-riate and multivariate Logistic regression analysis were used to analyze the influencing factors of poor progno-sis in patients with ACI-LAA.ROC curve was used to analyze the efficacy of serum miR-9-5p,miR-21-5p and miR-206 expression levels in predicting poor prognosis of patients with ACI-LAA.Results HT occurred in 74(27.92％)of 265 patients with ACI-LAA after thrombolysis.Compared with the non-HT group,the National Institutes of Health Stroke Scale(NIHSS)score atadmission,the proportion of hypertension,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were significantly in-creased in the HT group(P＜0.05).However,the expression level of serum miR-9-5p was decreased(P＜0.05).Hypertension,high NIHSS score at admission,the proportion of infarct size ≥10 cm2,high expression of miR-21-5p and miR-206 were risk factors for HT occurs in patients with ACI-LAA after intravenous thrombolysis,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that the area under the curve(AUC)and 95％CI of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting HT occurs were 0.796(0.726-0.866),0.779(0.711-0.846),0.784(0.714-0.854),0.891(0.839-0.943),respectively.Among 265 patients with ACI-LAA,83 patients(31.32％)had poor prognosis at 90 d of follow-up.Compared with the good prognosis group,the age,NIHSS score at admis-sion,the proportion of HT,the proportion of infarct size ≥10 cm2,and the expression levels of serum miR-21-5p and miR-206 were increased(P＜0.05),and the expression level of serum miR-9-5p was decreased(P＜0.05)in the poor prognosis group.Advanced age,high NIHSS score at admission,HT,infarct size ≥10 cm2,high expression of miR-21-5p,and high expression of miR-206 were risk factors for poor prognosis of ACI-LAA patients,and high expression of miR-9-5p was a protective factor(P＜0.05).The ROC curve showed that The AUC(95％CI)of single and combined detection of serum miR-9-5p,miR-21-5p and miR-206 for predicting poor prognosis were 0.754(0.691-0.818),0.779(0.719-0.838),0.792(0.815-0.919),0.931(0.902-0.960),respectively.Conclusion Low expression of serum miR-9-5p,high expression of miR-21-5p and high expression of miR-206 are associated with the HT occurs and poor prognosis in patients with ACI-LAA after thrombolysis,and the combined detection of the three indicators has a high predictive value for the HT occurs and poor prognosis.

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 explore the efficacy and safety of embolization of anterior cranial fossa dural arteriovenous fistula (ACF-DAVF) via different arterial approaches, and provide evidence for individualized treatment of ACF-DAVF. Methods:A retrospective study was performed; 25 patients with ACF-DAVF admitted to Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from January 2020 to December 2023 were enrolled. Vascular approaches, including the anterior cerebral artery ( n=7), facial artery ( n=3), middle meningeal artery ( n=8), ophthalmic artery ( n=6), and vein ( n=1), were selected based on angioarchitectural features and microcatheter accessibility. Fistula and proximal draining vein occlusions were confirmed by immediate post-embolization digital subtraction angiography (DSA), and perioperative complications were recorded. At a 6-month follow-up, prognoses were assessed by modified Rankin Scale (mRS), and DSA or MRA was performed to detect the recurrence of ACF-DAVF. Results:Six patients had complete embolization and 2 patients had near-total embolization of the fistula and proximal draining vein immediately after embolization via middle meningeal artery approach; 4 patients achieved complete embolization and 2 patients achieved near-total embolization via ophthalmic artery approach; 6 patients achieved complete embolization and one patient achieved near-total embolization via anterior cerebral artery approach; 3 patients achieved complete embolization via facial artery approach; one patient achieved complete embolization via venous approach. No perioperative intracranial hemorrhage or central retinal artery occlusion was noted. Follow-up for 6 months was performed in 25 patients: mRS score was 0 in 19 patients, 1 in 2 patients, and 2 in 4 patients; DSA in 19 patients and MRA in 6 patients indicated no ACF-DAVF recurrence. Conclusion:Based on the angioarchitectural features and microcatheter accessibility, individualized selection of vascular approaches for ACF-DAVF embolization can achieve better efficacy and safety.

Chronic migraine is a common episodic brain dysfunction disorder, which often progresses from migraine and is frequently accompanied by sleep disorders, anxiety, depression or obesity. Extensive connections exist between the hypothalamus and other components of the central nervous system; through integrating pain signals, neural conduction and inflammatory pathways, the hypothalamus becomes an important hub for migraine chronicization. This review, combined with clinical imaging evidence, analyzes the pathogenic mechanisms of chronic migraine and its complications from perspective of the hypothalamus as the higher neural center, so as to provide useful references for prevention and treatment of chronic migraine.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of Pseudomonas aeruginosa and ability to horizontally transfer across species. Methods:Clinical P. aeruginosa isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. Results:A total of 241 isolates of P. aeruginosa were gathered, and 35 blaOXA subtypes were identified through screening of 252 blaOXA genes. These genes were classified into three subfamilies: blaOXA-50-like (241, 95.6%), blaOXA-1-like (9, 3.6%) and blaOXA-10-like (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel blaOXA subtypes. Nine of these belonged to the blaOXA-50-like subfamily and were designated as blaOXA-1244, blaOXA-1245, blaOXA-1246, blaOXA-1250, blaOXA-1252, blaOXA-1253, blaOXA-1254, blaOXA-1255, and blaOXA-1256. The remaining two belonged to the blaOXA-10-like subfamily and were named blaOXA-1247 and blaOXA-1248. Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme′s ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the blaOXA genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: aac( 6′) -Ib-blaOXA-1247-ant( 3′′) -Ia, aac( 6′) -Ib-blaOXA-1248 and aac( 6′) -Ib- blaIMP-45-blaOXA-1-catB3. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS CR1 element to form a composite class I integron structure, additionally carrying the resistance gene blaPER-1. Out of the 223 non-wild-type P. aeruginosa strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. Conclusions:The blaOXA genes in 241 clinical P. aeruginosa strains showed diversity. Some blaOXA genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered blaOXA subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

Objectives:To evaluate the efficacies of laminoplasty(LP)and laminectomy and fusion(LF)in the treatment of multi-level ossification of the posterior longitudinal ligament(OPLL)in the cervical spine through meta-analysis.Methods:The databases of CNKI,Wanfang,Pubmed,Cochrane Library,EMBASE were searched by computer from their inceptions to June 2023 and the published clinical studies comparing LP and LF in the treatment of multi-level OPLL in the cervical spine were included.Cochrane risk bias assess-ment tool and Newcastle-Ottawa scale(NOS)were used to evaluate the quality of the included studies.Rele-vant data including operation time,intraoperative blood loss,the improvement rate of Japanese Orthopaedic Association(JOA)score,the change value of visual analogue scale(VAS)score,neck disability index(NDI),cer-vical curvature index(CCI),sagittal vertical axis(SVA)and cervical range of motion(CROM)at the final fol-low-up,the postoperative complication rate and OPLL progression rate were extracted and sorted.Then the meta-analysis was conducted by RevMan 5.4 and StataSE 16.0 softwares.Results:12 literatures(3 randomized controlled studies and 9 cohort studies)were ultimately included,involving a total sample size of 1496 cases,containing 839 cases in the LP group and 657 cases in the LF group.The results of meta-analysis were as follows:the LP group was better than LF group with significant differences in operation time[WMD=-28.01,95％CI(-36.25,-19.77),P＜0.00001],intraoperative blood loss[WMD=-115.09,95％CI(-197.91,-32.27),P=0.006],the change value of CROM[WMD=-7.83,95％CI(-8.10,-7.55),P＜0.00001]compared with those before surgery at final follow-up,the incidence of postoperative C5 nerve root paralysis[OR=0.32,95％CI(0.21,0.50),P＜0.00001]and axial symptoms[OR=0.44,95％CI(0.28,0.71),P=0.0006].The LF group was better than the LP group with significant differences in the change value of the CCI[WMD=-0.75,95％CI(-0.92,-0.58),P＜0.00001]and SVA[WMD=5.49,95％CI(5.30,5.68),P＜0.00001]compared with those before surgery at final follow-up,and the postoperative OPLL progression rate[OR=1.76,95％CI(1.26,2.46),P=0.0009].There were no significant differences between the two groups in the improvement rate of JOA score[WMD=-1.24,95％CI(-4.02,1.54),P=0.38],the change value of VAS[WMD=0.03,95％CI(-0.43,0.49),P=0.89]and NDI[WMD=0.54,95％CI(-0.07,1.14),P=0.08]compared with those before surgery at final follow-up,the incidence of postoperative cerebrospinal fluid leakage[OR=0.58,95％CI(0.24,1.39),P=0.22],incision infection[OR=0.71,95％CI(0.32,1.57),P=0.39]and epidural hematoma[OR=0.37,95％CI(0.06,2.16),P=0.27].Conclusions:Both LF and LP can effectively treat multi-level OPLL in the cervical spine and improve the neurological function of patients.Compared to LF,LP causes less surgical damage,preserves more cervical mobility and additionally,has a lower incidence of the postoperative C5 nerve root paralysis and axial symptoms.In comparison,LF can better maintain the curvature and stability of the cervical spine and delay the progression of ossification.