1.Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma
Huajie XIE ; Kai CHANG ; Yanyan WANG ; Wanlin NA ; Huan CAI ; Xia LIU ; Zhongyong JIANG ; Zonghai HU ; Yuan LIU
Journal of Clinical Hepatology 2025;41(2):284-291
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.
2.Effectiveness of arthroscopic release assisted with medial small incision in treatment of non-traumatic elbow stiffness.
Lijun LÜ ; Yanyan CHANG ; Baojun ZHOU ; Qiuming GAO ; Jieliang HU ; Liyuan CHEN ; Kongxing WEI ; Fujun GAO ; Wentao LI ; Xin YUAN ; Yibin JIN
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(5):563-568
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
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Elbow Joint/physiopathology*
;
Retrospective Studies
;
Range of Motion, Articular
;
Treatment Outcome
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Ulnar Nerve/surgery*
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Operative Time
3.Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence
Kai CHANG ; Yanyan WANG ; Zhongyong JIANG ; Wei SUN ; Chenxia LIU ; Wanlin NA ; Hongxuan XU ; Jing XIE ; Yuan LIU ; Min CHEN
Journal of Clinical Hepatology 2024;40(2):319-326
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.
4.Expert consensus on the genetic counseling for Dystrophinopathies
Xiaoliang LIU ; Yanyan ZHAO ; Hua WANG ; Jesse Ling LI ; Lingqian WU ; Yanping LU ; Qingxian CHANG
Chinese Journal of Medical Genetics 2024;41(6):651-660
Dystrophinopathies caused by variants of DMD gene are a group of muscular diseases including Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy. With the advancement of genetic testing techniques and wider implementation of genetic screening, especially the expanded carrier screening, more and more individuals carrying DMD gene variants have been identified, whereas the genetic counseling capacity is relatively insufficient. Currently there is still a lack of professional norms for genetic counseling on dystrophinopathies. In this consensus, the main points to be covered in the pre- and post-test consultation have been discussed, with an aim to provide genetic counseling guidance for the disease diagnosis, treatment, and family reproduction.
5.Combined ultrasound and clinical characteristics to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars
Yanjing CHEN ; Yongshuai QI ; Zhouyue JIANG ; Yanyan ZHANG ; Ting LANG ; Yue LIN ; Min CHANG ; Yingjia LI
Chinese Journal of Ultrasonography 2024;33(7):603-608
Objective:To combine ultrasound and clinical characteristics for predicting the treatment time of strontium 90( 90Sr) radioisotope applicator therapy for pathological scars when the therapeutic effect meets the clinical effective criteria. Methods:From September 2022 to October 2023, 48 patients (90 lesions) with pathological scars who underwent 90Sr radioisotope applicator therapy at the Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University were prospectively collected. The clinically effective criteria of 90Sr radioisotope applicator therapy for pathological scars were defined as a reduction of the superficial height of the scar higher than 50%. All lesions were divided into short period treatment group (2 months, 38 lesions) and long period treatment group (>2 months, 52 lesions) according to the duration of treatment when the therapeutic effect met the clinical criteria. Univariate comparative analyses of ultrasound and clinical characteristics between the two groups were performed. The statistically significant variates were used to build a multivariate logistic regression model for analyzing the independent predictors of the treatment time of 90Sr radioisotope applicator therapy for pathological scars. Results:Family history, blood flow signal, disease duration, age, and scar Young′s modulus were independent predictors of the effective treatment time of 90Sr radioisotope applicator therapy for pathological scars (all P<0.05). By using the selected variables, a predictive model was developed, area under the ROC curve (AUC) were 0.886 (95% CI=0.817-0.955, P<0.001), and the calibration curve showed that the model was well calibrated(χ 2=5.668, P=0.684). Conclusions:The multivariate logistic regression model with family history, blood flow signal, disease duration, age, and scar Young′s modulus could be used to predict the treatment time of 90Sr radioisotope applicator therapy for pathologic scars, which can help to guide the design of treatment plan, reduce unnecessary radiation damage, and improve patient compliance.
6.Research progress of choroidal vascular index in diabetic retinopathy
Xiaokun WANG ; Chao WU ; Yanyan CUI ; Weiwei CHANG ; Bojun ZHAO
Chinese Journal of Ocular Fundus Diseases 2023;39(12):1016-1021
Diabetic retinopathy (DR) is the main cause of blindness in diabetic patients. Early diagnosis and intervention are essential to improve the quality of life of patients with DR. Choroidal vascularity index (CVI) is the ratio of choroidal luminal area to total area, which can reflect the structure and blood flow of the choroid, and has been used to evaluate the choroidal condition in various eye diseases. CVI has shown great potential in the prediction, early intervention, disease assessment, and prognosis of DR. The relationship between CVI and photoreceptors needs more research, and CVI may be used as a predictive indicator of photoreceptor health and visual prognosis. In addition, the study of CVI at different layers of the choroid is limited by the accuracy of stratification and the repeatability of measurement. Artificial intelligence and other technologies may provide solutions for this. In the future, through more comprehensive study and the help of artificial intelligence, the value of CVI will be further enriched, which is of great significance for the elucidation of the pathogenesis of DR and serving the clinic.
7.Curative effect of wide pedicled double-vessel flap of posterolateral calf in repair of soft tissue defect in hind foot
Xiaowen DENG ; Lijun LYU ; Jie SHI ; Peng LIU ; Chuangbin LI ; Wenbo LI ; Wei WANG ; Yaqiang ZHANG ; Peisheng SHI ; Yun XUE ; Yanyan CHANG ; Qiuming GAO
Chinese Journal of Microsurgery 2023;46(1):32-38
Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.
8.Establishment of Specific Chromatogram and Thin-layer Identification Method for Kaixinsan
Wenya GAO ; Min FENG ; Chang GAO ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Ruipeng YU ; Yipeng ZHAO ; Lili ZHANG ; Yanqing GAO ; Yanhong XIAO ; Cuina CHENG ; Xiaolu WEI ; Nan SI ; Baolin BIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):37-44
ObjectiveTo establish the specific chromatogram and thin layer chromatography(TLC) identification method of Kaixinsan(KXS) samples, in order to clarify the key quality attributes and provide reference for the quality evaluation of KXS. MethodHigh performance liquid chromatography(HPLC) specific chromatogram of KXS was developed with YMC Hydrosphere C18 column(4.6 mm×250 mm, 5 μm), the mobile phase was acetonitrile(A)-0.2% formic acid aqueous solution(B) for gradient elution(0-15 min, 2%-20%A; 15-25 min, 20%-25%A; 25-30 min, 25%-30%A; 30-45 min, 30%-31%A; 45-50 min, 31%-44%A; 50-65 min, 44%-45%A; 65-73 min, 45%-75%A; 73-95 min, 75%-100%A; 95-105 min, 100%A; 105-105.1 min, 100%-2%A; 105.1-120 min, 2%A), the detection wavelength was 320 nm. Ultra high performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to identify the chemical components of KXS with electrospray ionization(ESI), negative ion mode and scanning range of m/z 50-2 000. TLC identification methods for Poria and Ginseng Radix et Rhizoma in KXS were established. ResultThere were 11 common peaks in the specific chromatogram of KXS, attributed to Polygalae Radix, Poria and Acori Tatarinowii Rhizoma. Taking peak 9(α-asarone) as the reference peak, the relative standard deviations of the retention times of 15 batches of KXS samples were<0.2%. A total of 34 compounds were identified by UHPLC-LTQ-Orbitrap MS, including terpenoids, phenylpropanoids, oligosaccharides and ketones. The established TLC had good separation and was rapid, reliable, simple, feasible, suitable for the identification of Poria and Ginseng Radix et Rhizoma in KXS. ConclusionThe specific chromatogram and TLC of KXS are stable and reproducible. The material basis of KXS is basically clarified by MS, which can provide a reference for the development and quality control of KXS.
9.Establishment of Specific Chromatogram and TLC Identification for Qingxin Lianziyin
Wenya GAO ; Xiujing MA ; Chang GAO ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Ruipeng YU ; Yipeng ZHAO ; Cuie YAN ; Lifang GAO ; Nan SI ; Baolin BIAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):34-42
ObjectiveTo establish the specific chromatogram and thin layer chromatography(TLC) of Qingxin Lianziyin(QXLZY) benchmark samples, in order to clarify the key quality attributes and provide a reference for the quality evaluation of QXLZY. MethodHigh performance liquid chromatography(HPLC) specific chromatogram of QXLZY benchmark samples was developed by using a YMC Hydrosphere C18 column(4.6 mm×250 mm, 5 μm) with the mobile phase of acetonitrile(A)-0.2% formic acid aqueous solution(B) for gradient elution(0-10 min, 5%-20%A; 10-20 min, 20%A; 20-25 min, 20%-24%A; 25-40 min, 24%-30%A; 40-55 min, 30%-50%A; 55-65 min, 50%-100%A; 65-75 min, 100%A; 75-75.1 min, 100%-5%A; 75.1-90 min, 5%A), and the detection wavelength was 360 nm. Ultra-high performance liquid chromatography-linear ion trap/orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) with electrospray ionization(ESI) was used to identify the components of QXLZY benchmark samples by accurate relative molecular weight and multilevel MS fragment ion information, the detection conditions were positive and negative ion modes and data dependency scanning mode. TLC identification methods for Ophiopogonis Radix, Lycii Cortex, Nelumbinis Semen, Poria, Astragali Radix and Ginseng Radix et Rhizoma in QXLZY were established. ResultA total of 15 characteristic peaks were identified from Glycyrrhizae Radix et Rhizoma, Plantaginis Semen and Scutellariae Radix, and the relative standard deviations of the retention times of 15 characteristic peaks in 15 batches of QXLZY benchmark samples were≤3% with peak 8(baicalin) as the reference peak. A total of 100 compounds, including flavonoids, organic acids, saponins, amino acids and others, were identified in the benchmark samples by UHPLC-LTQ-Orbitrap MS. The established TLC had good separation and was suitable for the identification of Ophiopogonis Radix, Lycii Cortex, Nelumbinis Semen, Poria, Astragali Radix and Ginseng Radix et Rhizoma in QXLZY. ConclusionThe material basis of QXLZY benchmark samples is basically determined by MS designation and source attribution. The established specific chromatogram and TLC of QXLZY are simple, stable and reproducible, which can provide a reference for the development and quality control of QXLZY.
10.A study on the mechanism of Avilamycin intervention MTIF2 regulating ribosomal translation process to inhibit hepatitis B virus replication
Kai Chang ; Wanlin Na ; Chenxia Liu ; Zhongyong Jiang ; Yanyan Wang ; Hongxuan Xu ; Jinlan Shen ; Yuan Liu
Acta Universitatis Medicinalis Anhui 2022;57(2):203-207
Objective :
To investigate the inhibitory effect and molecular mechanism of ribosomal translation factor inhibitor Avilamycin on hepatitis B virus replication.
Methods:
Liver cancer Hep3B cells were treated with different concentrations of Avilamycin. Cell activity was detected by CCK⁃8 ; the apoptosis was detected by flow cytometry , and HBV⁃DNA、pgRNA、MTIF2、RPL10 gene expression level was detected by qPCR method. The HBsAg and HBeAg was detected by ELISA. The AFP was detected by chemiluminescence. Aspartate aminotransferase (AST) , alanine aminotransferase(ALT) , and alkaline phosphatase (ALP) proteins was detected by Biochemistry method.
Results :
Avilamycin had no inhibitory effect on Hep3B cell proliferation and apoptosis. However, it could promote
cellular AST secretion , reduce AFP levels , and have less effect on ALP secretion. In Hep3B cells , Avilamycin promotes accumulation of pgRNA expression by intervening with MTIF2 and feedback upregulates mRNA expression of host RPL10 and MTIF2 genes. It can effectively reduce the HBsAg , HBeAg , and HBV - DNA levels.
Conclusion
Avilamycin can inhibit MTIF2 translation initiation , regulate the translation process of viral assembly protein by affecting translation initiation , and then inhibit hepatitis B virus replication.


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