1.VIRMA-mediated SHQ1 m6A modification enhances liver regeneration through an HNRNPA2B1-dependent mechanism.
Hao CHEN ; Haichuan WANG ; Jiwei HUANG ; Guoteng QIU ; Zheng ZHANG ; Lin XU ; Xiao MA ; Zhen WANG ; Xiangzheng CHEN ; Yong ZENG
Acta Pharmaceutica Sinica B 2025;15(10):5212-5230
N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl4) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.
2.Promoting Reform of Talent Evaluation Based on China Clinical Cases Library of Traditional Chinese Medicine
Kaige ZHANG ; Yong ZHU ; Jisheng WANG ; Liangzhen YOU ; Weijun HUANG ; Jie YANG ; Candong LI ; Genping LEI ; Chuan ZHENG ; Shuzhen GUO ; Longtao LIU ; Zhining TIAN ; Xinping QIU ; Wenli SU ; Zuo LI ; Wei YAN ; Hongcai SHANG ; Xiaoxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):220-226
Talents are the main force for the development of traditional Chinese medicine(TCM), and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present, we are still exploring and developing in the fields of the formulation, implementation and evaluation indicators of TCM talent evaluation system. However, there are shortcomings and difficulties. For instance, insufficient stratification in the evaluation, excessive emphasis on the quantity of achievements, neglecting the quality of the achievements and the actual contribution, imperfect assessment indicators, and the weak characteristics of TCM. Therefore, national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard, in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value, ability and contribution. For the evaluation of TCM clinical talents, China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM(CCCL-TCM), which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry, and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.
3.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
4.Measurement of the diameter of the corpus callosum in children on the midsagittal plane of MRI
Kuan LU ; Jie DENG ; Yong ZHENG ; Lihua QIU
Journal of Practical Radiology 2024;40(4):629-632,658
Objective To measure the diameter of the corpus callosum in children aged 0-14 years using midsagittal high-resolution MRI,and to find the normal reference values of the diameter of the corpus callosum in children of different ages.Methods The imaging data of 967 children with normal brain MRI were retrospectively selected and grouped according to age.The anteroposterior diameter(APD),thickness of the genu(GT),thickness of the body(BT),thickness of the isthmus(IT),thickness of the splenium(ST)and fronto-occipital diameter(FOD)of the corpus callosum were measured on the midsagittal plane of the brain.The diameters of the corpus callosum on the midsagittal plane of the brain of children at different ages were measured.The correlation analysis between the diameter of the corpus callosum and age were performed.Results The APD,GT,BT,IT,ST and FOD were positively correlated with age(r=0.660,0.590,0.528,0.521,0.660,0.597,P<0.01).The IT variation was the greatest in the subregions of the corpus callosum.The growth peak of GT and ST of corpus callosum appeared before 2 years of age.Conclusion The establishment of the normal reference value of different subregions of the corpus callosum in children can help to accurately evaluate the development of the corpus callosum,which is conducive to the evaluation of the prognosis of diseases related to the corpus callosum.
5.Antimicrobial resistance and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli from human and food samples in Henan Province
Hao-Yu QI ; Yan-Fen LI ; Yu WANG ; Zheng-Yong QIU ; Ying CUI ; Ling-Ling WU ; Meng ZHANG ; Yong-Li LI
Chinese Journal of Zoonoses 2024;40(8):723-731
This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1%),followed by tetracycline(79.2%)and nalidixic acid(64.4%).The resistance rate to cefotaxime was 38.6%.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).
6.Factors for low libido in male patients with sexual dysfunction
Qiu-Chen LÜ ; Rui WANG ; Zu-Long WANG ; Tian-Ji ZHANG ; Tao ZHENG ; Kun-Long LÜ ; Yong-Hao NAN
National Journal of Andrology 2024;30(8):734-737
Objective:To analyze the factors for low libido in male patients with sexual dysfunction and provide some evidence for the clinical diagnosis and treatment of the condition.Methods:We retrospectively analyzed the clinical data on 111 cases of sex-ual dysfunction(including disorders in erection,ejaculation or libido)treated in the Zhengzhou University First Hospital from June to September 2023.According to the patients'complaints of low libido or accompanied symptoms,we divided them into a normal libido group(n=68)and a low libido(n=43),obtained their scores on IIEF-5,Premature Ejaculation Diagnostic Tool(PEDT),13-1-tem Self-Rating Libido Scale for Males(SRLS-M),Patients'Health Questionnaire-9(PHQ-9)and General Anxiety Disorder-7(GAD-7),examined the levels of the sexual hormones FSH,LH,PRL,T,free testosterone(fT),E2,?insulin-like growth factor 1(IGF-1)and growth hormone(GH),compared the basic parameters between the two groups,and analyzed their correlation with the libido values.Results:The IIEF-5,PEDT and libido scores and IGF-1 level were significantly higher and the GAD-7 score remark-ably lower in the normal than in the low libido group(P<0.05),but no statistically significant differences were observed between the two groups in the PHQ-9 score and the levels FSH,LH,PRL,T,fT,E2,T/E2 and GH(P>0.05).The libido value was correla-ted positively with the I1EF-5(r=0.28,P<0.01)and PEDT scores(r=0.29,P<0.01)and IGF-1 level(r=0.23,P<0.05),but negatively with the GAD-7 score(r=-0.21,P<0.05).Conclusion:Low libido results from multiple factors,which cannot be fully explained by sexual hormone levels but is closely related to the decreased level of IGF-1 and severity of ED and anxiety.
7.Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1.
Xue-Li WANG ; Xiao-Zheng CAO ; Dao-Yuan WANG ; Ye-Bei QIU ; Kai-Yu DENG ; Jian-Guo CAO ; Shao-Qiang LIN ; Yong XU ; Kai-Qun REN
Chinese journal of integrative medicine 2023;29(3):224-232
OBJECTIVE:
To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.
METHODS:
Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).
RESULTS:
DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.
CONCLUSION
CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Female
;
Humans
;
Cell Line, Tumor
;
HeLa Cells
;
Neoplastic Stem Cells/metabolism*
;
RNA, Small Interfering/metabolism*
;
Uterine Cervical Neoplasms/metabolism*
9.A comparative study for the efficacies of transaxillary non-inflatable endoscopic surgery versus traditional surgery for papillary thyroid carcinoma.
Xiao Lei CHEN ; Chao LI ; Yu Qiu ZHOU ; Yong Cong CAI ; Yu Dong NING ; Chun Yan SHUI ; Xu WANG ; Zi Xun ZENG ; Gang QIN ; Ming Hua GE ; Chuan Ming ZHENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(4):351-357
Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs. 20 (10) ml, M (IQR), Z=-2.22], postoperative drainage volumes [170 (70)ml vs. 101 (55)ml, Z=-7.91], operative time [135 (35)min vs. 95 (35)min, Z=-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs. (25 643.5±2 610.7)yuan, x¯±s, t=0.73], postoperative hospitalization time [(3.1±0.9)days vs. (2.6±0.9)days, t=-3.24], and drainage tube placement time [(2.5±0.8) days vs. (2.0±1.0)days, t=-4.16], with statistically significant differrences (all P<0.05). There was no significant difference in surgical complications (P>0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P<0.05), while there were no statistically significant differences in other quality of life scores (all P>0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference (χ2=41.47, P<0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.
Male
;
Female
;
Humans
;
Thyroid Cancer, Papillary/surgery*
;
Retrospective Studies
;
Quality of Life
;
Thyroid Neoplasms/pathology*
;
Endoscopy
;
Thyroidectomy/methods*
10.Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome.
Ming Sheng MA ; Zhi YANG ; Cai Hui ZHANG ; Yao Yao SHANGGUAN ; Yong Zhen LI ; Mei Fang ZHU ; Cui BAI ; Yu ZHOU ; Qiu Ye ZHANG ; Hai Guo YU ; Xiao Chuan WU ; Wen Jie ZHENG ; Jun YANG ; Hong Mei SONG
Chinese Journal of Pediatrics 2023;61(12):1098-1102
Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.
Male
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Child
;
Female
;
Humans
;
Child, Preschool
;
Receptors, Tumor Necrosis Factor, Type I/genetics*
;
Retrospective Studies
;
Hereditary Autoinflammatory Diseases/drug therapy*
;
Glucocorticoids/therapeutic use*
;
Biological Factors/therapeutic use*
;
Immunosuppressive Agents/therapeutic use*
;
Autoantibodies
;
Familial Mediterranean Fever/diagnosis*
;
Mutation

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