ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

OBJECTIVE: To explore the effectiveness of arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release in the treatment of non-traumatic elbow stiffness. METHODS: The clinical data of 15 patients with non-traumatic elbow stiffness treated with arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release between April 2019 and September 2023 were retrospectively analyzed. There were 6 males and 9 females with an average age of 46 years ranging from 34 to 56 years. The causes included rheumatoid arthritis in 3 cases, gouty arthritis in 2 cases, loose bodies in 3 cases, and elbow osteoarthritis in 7 cases. There were 4 cases with ulnar neuritis and 3 cases with synovial osteochondromatosis. The duration of elbow stiffness ranged from 6 to 18 months, with an average of 10 months. The operation time and intraoperative blood loss were recorded. The effectiveness was evaluated by visual analogue scale (VAS) score, range of elbow motion (maximum flexion, maximum extension, and total flexion and extension), Mayo score, and Hospital for Special Surgery (HSS) elbow score. RESULTS: The operation time was 60-90 minutes, with an average of 65 minutes, and the intraoperative blood loss was 40-100 mL, with an average of 62 mL. All patients were followed up 13-18 months, with an average of 14 months. There was no complication such as vascular and nerve injury, poor wound healing, collateral ligament injury, elbow joint space narrowing, osteophyte proliferation, or loose body formation around the joint. At last follow-up, the elbow range of motion (maximum flexion, maximum extension, and total flexion and extension), VAS score, and Mayo score significantly improved when compared with those before operation ( P<0.05). The HSS elbow score was 85-95, with an average of 92; 12 cases were excellent, 3 cases were good, and the excellent and good rate was 100%. CONCLUSION Arthroscopic release of elbow joint assisted by medial small incision ulnar nerve release is an effective way to treat non-traumatic elbow stiffness, which has the advantages of small trauma, short operation time, and good effectiveness. It can carry out early elbow rehabilitation training and significantly improve elbow function.
Humans ; Male ; Female ; Arthroscopy/methods* ; Adult ; Middle Aged ; Elbow Joint/physiopathology* ; Retrospective Studies ; Range of Motion, Articular ; Treatment Outcome ; Ulnar Nerve/surgery* ; Operative Time

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Objective To investigate the effect of resveratrol(RSV)in the treatment of peri-implantitis in a murine model and its effect on nuclear factor kappa-B(NF-κB)signaling and mitogen-activated protein kinase(MAPKs)signal-ing.Methods This study has been reviewed and approved by the Ethics.After extracting the right maxillary molars of 40 C57BL/6 mice and allowing them to heal naturally for 8 weeks,implants were implanted at the site of the first molar.The mice were randomly divided into a control group,a mouse peri implantitis model group,a low-dose group of 20 mg/kg resveratrol(RSV-L),and a high-dose group of 40 mg/kg resveratrol(RSV-H).After 4 weeks of implant implantation,a silk thread ligation induced peri implantitis model was established in all mice except for the control group.The model group received intervention with physiological saline by gavage,while the drug group received intervention with resvera-trol by gavage for 6 consecutive weeks.After 6-week treatment,observe the swelling of the gums around the implant and measure the bone resorption around the mouse implant using micro CT.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor alpha(TNF-α)and interleukin-6(IL-6)in gingival crevicular fluid.HE staining was used to observe the infiltration of inflammatory cells in the surrounding tissues of mouse implants.Pro-tein expression level and phosphorylation level of extracellular regulated protein kinases(ERK),p-ERK,c-Jun N-termi-nal kinase(JNK),p-JNK,p38 mitogen activated protein kinase(p38 MAPK),p-p38MAPK,nuclear factor kappa-B(NF-κB),p-NF-κB,nuclear factor-κB inhibitory protein(IκBα),p-IκBα in MAPKs/NF-κB signaling pathway were detected by Western blot(WB).Results Resveratrol group showed reduced tissue edema and decreased alveolar bone resorp-tion.Among them,the high-dose resveratrol group had lighter tissue edema and weaker bone resorption compared to the low-dose group.The micro CT results showed that significant changes in the bone level around the implant were observed in the model group mice at four sites:proximal,distal,buccal,and palatal.High dose resveratrol intervention reduced al-veolar bone resorption(P＜0.05);compared with the low-dose group,the high-dose group showed a decrease in palatal bone resorption(P＜0.05),while there was no significant difference in absorption between the mesial,distal,and buccal sides(P＞0.05).The ELISA results showed that compared with the model group,the levels of TNF-α and IL-6 in the gingival crevicular fluid of mice in the low-dose and high-dose resveratrol groups were lower(P＜0.05).The IL-6 in the gingival crevicular fluid of mice in the high-dose resveratrol group was lower than that in the low-dose group(P＜0.05).However,there was no significant difference in TNF-α levels between the two groups.HE staining showed a decrease in inflammatory cell infiltration in mice after treatment with resveratrol.The WB results showed that compared with the con-trol group,the expression levels of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB phosphorylated proteins in the gingi-val tissue of the model group mice were significantly increased(P＜0.01).The resveratrol treatment group significantly inhibited the phosphorylation of p-Erk,p-JNK,p-p38MAPK,p-IκA,and p-NF-κB proteins.Compared with the low-dose group,the high-dose group inhibited the phosphorylation of MAPKs/NF-κB signaling pathway related proteins more sig-nificantly(P＜0.05).Conclusion Resveratrol protect ligature induced peri-implantitis murine model,which may be re-lated to its inhibition of phosphorylation of MAPKs/NF-κB pathway.

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Pulmonary sarcomatoid carcinoma(PSC)is a rare and highly malignant tumor,which includes the follow-ing five pathologic types:pleomorphic carcinoma,spindle cell carcinoma,giant cell carcinoma,carcinosarcoma and pulmonary blastoma.The onset of PSC is occult with non-specific clinical symptoms and signs.The clinical manifestations include irritat-ing cough,bloody sputum,dyspnea,chest pain and so on,which are closely related to the growth and invasion site of the tumor.PSC tends to metastasize early,so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit.A patient with primary PSC which led to 90%stenosis in central airway was treated by com-bined method of vascular and tracheoscopic intervention in our respiratory center.This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery.Herein we report the case for clinical reference.

Background and objective As a new technique developed in recent years,bronchoscopic interven-tion therapy has the advantages of minimal invasion,high safety and repeatability.The aim of this study is to investigate the clinical characteristics of bronchopleural fistula(BPF)induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF,so as to provide support for prevention and treatment of BPF.Methods Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Cen-ter of Dongzhimen Hospital,Beijing University of Chinese Medicine from June 2020 to September 2023 were collected.Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol,combined with blocking therapy with N-butyl cyanoacrylate,medical bioprotein glue or silicone prosthesis.Patients with fistula diameter＞5 mm were im-planted with different stents and cardiac occluders.Locations and characteristics of fistulas were summarized,meanwhile,data including Karnofsky performance status(KPS),shortbreath scale(SS),body temperature,pleural drainage volume and white blood cell count before and after operation were observed.Results For all 64 patients,96 anatomic lung resections in-cluding pneumonectomy,lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations.The proportion of fistula in the right lung(63.5％)was significantly higher than that in the left(36.5％).Besides,the right inferior lobar bronchial fistula was the most common(40.5％).After operation,KPS was significantly increased,while SS,body tem-perature,pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values(P＜0.05).By telephone follow-up or readmission during 1 month to 38 months after treament,median survival time was 21 months.33 patients(51.6％)showed complete response,7 patients(10.9％)showed complete clinical response,18 patients(28.1％)showed partial response,and 6 patients(9.4％)showed no response.As a whole,the total effective rate of broncho-scopic intervention for BPF was 90.6％.Conclusion BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating.Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Pulmonary mixed squamous cell and glandular papilloma(MSCGP)is a subtype of pulmonary papil-loma,which can be classified as central type and peripheral type based on its site of development.The central type is the most common.The clinical manifestations of pulmonary MSCGP are mainly related to the location of the tumor.Surgery is the main treatment for this disease.Bronchoscopic interventional treatment for the MSCGP in the central trachea could receive satis-factory effect.We reported a patient suffered from diffuse tracheal MSCGP who was treated by bronchoscopic interventional treatment in Respiratory Disease Center,Dongzhimen Hospital of Beijing University of Chinese Medicine,aiming to enhance the recognition of the clinical features and provide clinical references for the diagnosis and treatment of such disease.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.