1.Research Progress on the Mechanism of Lipocalin-2 in Neurological Diseases
Yongtai ZHOU ; Zhenyu YANG ; Yan LI ; Jiajing WU ; Bo ZHAO
Medical Journal of Peking Union Medical College Hospital 2025;16(2):330-337
Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.
2.Efficacy of the far lateral Key-hole technique in the treatment of central cervical disc herniation.
Zhenyu MENG ; Jingbo XUE ; Xuelin LI ; Zhun XU ; Jinghua TAN ; Yong XIE ; Yiguo YAN
Journal of Central South University(Medical Sciences) 2025;50(8):1408-1417
OBJECTIVES:
In the early stage of central cervical disc herniation, clinical symptoms may be mild. However, as the spinal cord becomes compressed by herniated nucleus pulposus tissue, progressive edema and degeneration may occur, resulting in more severe clinical manifestations, including limb weakness, bladder and bowel dysfunction, spastic paraplegia of the lower extremities, and even respiratory difficulty. The spinal endoscopic Key-hole technique is widely applied in treating radiculopathic cervical spondylosis and has demonstrated good clinical outcomes. This study aims to analyze and summarize the technical points and therapeutic efficacy of the far lateral Key-hole technique in the treatment of central cervical disc herniation, providing reference for clinical application.
METHODS:
Eight patients with central cervical disc herniation treated with the far lateral Key-hole technique were included as the experimental group. Another 8 patients who underwent single-level anterior cervical diskectomy and fusion (ACDF) during the same period were selected as the control group. Data collected included gender, age, intraoperative blood loss, incision length, and length of hospitalization. Pain severity was evaluated using the Visual Analogue Scale (VAS); cervical function was assessed using the Japanese Orthopaedic Association (JOA) score; and cervical disability was measured by the neck disability index (NDI). Radiological outcomes were assessed using disc height index (DHI), cervical Cobb angle, and operative segment Cobb angle.
RESULTS:
Compared with the control group, the experimental group had significantly less intraoperative blood loss, shorter incision length, and shorter hospital stay (all P<0.05), while there was no significant difference in operation time (P>0.05). Postoperative VAS and NDI scores in both groups were significantly lower than preoperative values, and JOA scores significantly improved (P<0.05). No significant differences were noted between the two groups preoperatively (P>0.05). Postoperatively, the experimental group showed significantly lower VAS and NDI scores and higher JOA scores than the control group (P<0.05). There was no statistical significance in DHI before and after surgery in the experimental group (P>0.05), while the DHI increased significantly postoperatively in the control group (P<0.05). Postoperative DHI in the experimental group was significantly lower than in the control group (P<0.05). No significant differences were observed in the cervical Cobb angle either within or between groups (all P>0.05). The operative segment Cobb angle increased significantly after surgery in the control group (P<0.05), while no other operative segment angle changes were statistically significant (all P>0.05).
CONCLUSIONS
The far lateral Key-hole technique offers advantages in treating central cervical disc herniation, including reduced intraoperative bleeding, smaller incision length, shorter hospitalization, and improved postoperative pain relief. Additionally, the technique does not affect cervical physiological curvature or stability in the short term, making it suitable for clinical application.
Humans
;
Intervertebral Disc Displacement/surgery*
;
Cervical Vertebrae/surgery*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Diskectomy/methods*
;
Treatment Outcome
;
Spinal Fusion/methods*
;
Endoscopy/methods*
3.m6A modification regulates PLK1 expression and mitosis.
Xiaoli CHANG ; Xin YAN ; Zhenyu YANG ; Shuwen CHENG ; Xiaofeng ZHU ; Zhantong TANG ; Wenxia TIAN ; Yujun ZHAO ; Yongbo PAN ; Shan GAO
Chinese Journal of Biotechnology 2025;41(4):1559-1572
N6-methyladenosine (m6A) modification plays a critical role in cell cycle regulation, while the mechanism of m6A in regulating mitosis remains underexplored. Here, we found that the total m6A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m6A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m6A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m6A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m6A modification inhibits PLK1 translation via YTH N6-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m6A in regulating mitosis and the potential of m6A as a therapeutic target in proliferative diseases such as cancer.
Humans
;
Polo-Like Kinase 1
;
Cell Cycle Proteins/metabolism*
;
Proto-Oncogene Proteins/metabolism*
;
Protein Serine-Threonine Kinases/metabolism*
;
Mitosis/physiology*
;
HeLa Cells
;
Adenosine/genetics*
;
Methyltransferases/metabolism*
;
RNA, Messenger/metabolism*
;
RNA-Binding Proteins/metabolism*
4.Antibacterial magnesium oxide-calcium phosphate composite coating prepared by combining electrodeposition and sol-gel impregnation
Junjie TAN ; Jiaheng DU ; Zhenyu WEN ; Jiyuan YAN ; Kui HE ; Ke DUAN ; Yiran YIN ; Zhong LI
Chinese Journal of Tissue Engineering Research 2024;28(29):4663-4670
BACKGROUND:Calcium phosphate(CaP)coatings are widely used to improve the integration of titanium implants into bone but these coatings are associated with risks of infection.It is thus desirable to confer antibacterial properties to CaP coatings. OBJECTIVE:To prepare CaP-MgO composite coatings by impregnating magnesium oxide(MgO)sol into CaP coatings and assess the in vitro antibacterial activities and cytocompatibility. METHODS:An electrolyte was determined by titration and used for CaP coating electrodeposition on titanium(referred to as Ti-CaP).MgO was impregnated into the coating by immersing in an MgO sol with different mass fractions(15%,30%,50%)and subsequently calcined to form MgO-CaP composite coatings,which were recorded as Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg,respectively.Microstructure,tensile properties,critical load,and Mg2+ release of coatings in vitro were characterized.Antibacterial activity was assayed using spread plate method by culturing S.aureus on the pure titanium sheet surface and Ti-CaP,Ti-Cap-15mg,Ti-Cap-30mg and Ti-Cap-50mg surfaces for 24 and 48 hours.Mouse osteoblast suspension was inoculated on pure titanium sheets and Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg coated titanium sheets,respectively.Cell proliferation was detected by CCK-8 assay,and cell survival rate was calculated.The morphology of composite coating soaked in DMEM was also observed. RESULTS AND CONCLUSION:(1)Homogeneous,microporous CaP coatings consisting of octacaclium phosphate crystal flakes were prepared on titanium by electrodeposition.After sol impregnation-calcination,MgO aggregates were filled into the inter-flake voids.The extent of MgO filling and Mg concentration in the coating increased with the number of sol impregnation procedures.When immersed in phosphate buffered saline,all composite coatings actively released Mg2+ within 1 day;subsequently,the Mg2+ release slowed down on day 3.A small amount of Mg2+ release was still detected on day 7.The yield strength,tensile strength and fracture growth rate of Ti-CaP-30Mg coated titanium were not significantly different from those of pure titanium(P>0.05).There was no significant difference in the critical load of Ti-CaP,Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups(P>0.05).(2)Except that pure titanium sheet and Ti-CaP had no antibacterial properties,the other samples had good antibacterial properties,and the antibacterial rate increased with the increase of MgO content in the coating.(3)After 1 and 3 days of co-culture,the cell survival rate of Ti-CaP-15Mg,Ti-CaP-30Mg and Ti-CaP-50Mg groups was lower than that of pure titanium group and Ti-CaP group(P<0.05).After 5 and 7 days of culture,there was no significant difference in cell survival rate among five groups(P>0.05).The content of MgO in the coating decreased gradually with the time of immersion in the medium.(4)The MgO sol impregnation added antibacterial properties to the CaP coatings while retained their biocompatibility.
5.Protective role of intestinal microbial network in hyperoxaluria-induced kidney impairment in rats
Yan WANG ; Tiejun PAN ; Zhenyu LIU ; Jinbo SUN ; Yu ZHOU ; Chaosheng LI ; Lei GAO
The Journal of Practical Medicine 2024;40(13):1771-1777
Objective To explore the effects of fecal microbiota transplantation(FMT)on oxalate metabolism and renal protection in rats fed a high oxalate diet.Methods Twenty-four male SD rats were randomly divided into four groups:SC,SC+FMT,OD+PBS and OD+FMT.The SC group was set as the control group and was fed standard rat chow.The OD+PBS group and OD+FMT group were fed a diet containing 5%oxalate.Starting from day 14,the OD+PBS group,OD+FMT group and SC+FMT group received intragastric administration of PBS solution or filtered faecal microbiota solution from guinea pigs for 7 consecutive days.The 24-hour urine,feces,and venous serum of the rats were collected from the rats of all groups to determine the gut microbiota and biochemical markers.Real-time quantitative PCR and immunohistochemistry were conducted on the rat kidneys to detect the expression of renin,ACE,and OPN.Results The fecal microbiota transplantation altered the gut microbiota of rats.The gut microbiota of the SC+FMT group deviated from that of the SC group and showed increased similarity to that of the guinea pigs.Compared to the OD+PBS group,the OD+FMT group exhibited significant reductions in the urinary oxalate,urinary urea,uric acid,urinary creatinine,serum urea nitrogen/creati-nine,and serum uric acid.Furthermore,after FMT treatment,the OD+FMT group exhibited reduced upregulation of renin mRNA expression and restored downregulation of OPN mRNA expression compared to the OD+PBS group;similar results were obtained from immunohistochemistry.Conclusion Fecal microbiome trans-plantation activated the microbial network in the rat gut,particularly the oxalate-degrading bacteria represented by Muribaculaceae.The kidney injury induced by high oxalate was partially restored by the microbiota network's degradation of oxalate,indicating the protective effect of fecal microbiota transplantation on the rat kidneys.
6.Effects of dietary restriction combined with different exercises on inflammatory factors and gut microbiota in obese children
WANG Peng, LIU Baoliang, HU Zhenyu, LIU Yan, JIANG Di,ZHANG Ping
Chinese Journal of School Health 2024;45(6):794-798
Objective:
To compare the effects of aerobic exercise, resistance training, and a combination of aerobic exercise and resistance training (combined exercise) with dietary restrictions on inflammatory factors and gut microbiota in obese children, so as to provide the reference for improving the health level of obese children.
Methods:
From August to September 2022, a total of 70 obese children aged 10-12 from the Affiliated Experimental Primary School of Minjiang Normal University were recruited through online notifications and WeChat distribution through parent groups. Participants were divided into dietary restriction (DR, n=18) group, aerobic exercise combined with dietary restriction (AE+DR, n=18) group, resistance training combined with dietary restriction (RT+DR, n=17) group and combined exercise combined with dietary restriction (ART+DR, n=17) group,through random number table method. From September to November 2022, each group received different interventions.The daily dietary intake of calories in the DR group was determined according to resting energy consumption. The AE+DR group intervention mainly included skipping rope, aerobics exercises, jogging and sports games, and were maintained for each session lasting 50 minutes. For RT+DR group, the exercise intensity of resistance training was (65%-85%) maximum strength, with a total of 10 actions. The ART+DR group included resistance training (20 minutes), aerobic exercise (20 minutes), preparation and relaxation phases for 5 minutes each. The DR and exercise intervention was administered for 8 weeks (4 times a week for Monday, Tuesday, Thursday and Friday). Before and after different intervention methods, serum inflammatory factors were detected by enzymelinked immunosorbent assay (ELISA) and intestinal flora was calculated by plate colony counting method.
Results:
Compared to those before intervention, the levels of serum TNF-α, IL-6 and CRP, and the contents of enterococcus and escherichia coli in the faeces significantly decreased, while the contents of lactobacillus and bifidobacterium in the faeces significantly increased after intervention (t=7.19,7.15,4.57,5.42,5.15,-3.51,-7.30;5.14,3.64,3.02,3.27,5.00,-3.09,-3.75;7.10,10.86,7.74,10.92,9.26,-6.63,-6.33,P<0.05) in AE+DR, RT+DR and ART+DR groups. The levels of serum TNF-α and CRP and enterococcus decreased significantly, and the contents of lactobacillus and bifidobacterium in the faeces increased significantly after intervention (t=2.74, 2.22, 2.14, -2.21, -2.81, P<0.05) in the DR Group. After 8 weeks of intervention with different methods, the change differences of enterococcus, escherichia coli, lactobacillus, bifidobacterium in the faeces, and serum TNF-α, IL-6 and CRP levels were statistically significantin the four groups of obese children (H=22.22, 23.75, 13.44, 28.33, 18.02, 33.64, 25.14, P<0.01). In addition, the decreases of enterococcus in the faeces and serum TNF-α, IL-6, CRP levels, and the increases of lactobacillus in the faeces were significantly higher than those in the other three groups.
Conclusions
Dietary restriction alone or combined with different exercises bring beneficial changes in the inflammatory factors and gut microbiota indicators in obese children. Combined exercise,as well as aerobic exercise combined with dietary restrictions are more reasonable and effective in obese children.
7.Interaction effect between vitamin D and gestational diabetes mellitus in the second trimester
Ziwen MA ; Xiaoying DING ; Liming CHU ; Yan ZHANG ; Aifeng ZHANG ; Yanjun ZHU ; Xun WANG ; Zhenyu XIE
Shanghai Journal of Preventive Medicine 2024;36(11):1094-1099
ObjectiveTo investigate the relationship between serum 25(OH)D and gestational diabetes mellitus in the second trimester (GDM), to analyze the interaction effect of key risk factors, so as to provide a basis for clinical personalized vitamin D supplementation. MethodsA total of 266 pregnant women who registered and took regular obstetric check-ups in Shanghai Pudong New Area Health Care Hospital for Women and Children from June to December 2022, were selected as the research subjects. According to the results of oral glucose tolerance test (OGTT), the subjects were divided into the GDM group (131) and control group (135). The level of serum 25(OH)D at the time of OGTT were detected and other clinical indicators were followed up. ResultsThe age, systolic blood pressure in early pregnancy, pre-pregnancy BMI, FPG, OGTT 1-hour and 2-hour glucose, GHb, HOMA-IR, TG, AST, Cr, D-D, FDP and SF at 35 weeks’ gestation of the pregnant women were higher in the GDM group than that of the pregnant women in the normal group, while gestational weight gain and serum 25(OH)D level were significantly lower than that of the pregnant women in the normal group. Serum 25(OH)D was negatively correlated with HOMA-IR and WBS’s, but positively correlated with TG and ALT. Serum 25(OH)D was non-linearly correlated with the risk of GDM in an inverted J-shape, and there was an interaction effect of advanced age, pre-pregnancy obesity and vitamin D deficiency on the risk of GDM. ConclusionVitamin D is non-linearly associated with the risk of GDM. The risk of GDM is significantly reduced when serum 25(OH)D level ≥30 ng∙mL-1.
8.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
9.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.
10.Construction of a prediction model for postoperative prognosis in patients with resectable cholangiocarcinoma based on silence information regulator 2 expression
Wei WANG ; Wenbin JI ; Zhenyu LYU ; Wanliang SUN ; Yu SHAO ; Jing LIU ; Yan YANG
Journal of Zhejiang University. Medical sciences 2024;53(1):98-107
Objective:To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma(CCA)based on the expression of silence information regulator 2(SIRT2).Methods:The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases.Gene set enrichment analysis(GSEA)was used to explore potential mechanisms of SIRT2 in CCA.The expression of SIRT2 protein in CCA tissues and normal tissues(including 44 pairs of specimens)was also detected by immunohistochemistry(IHC)in 89 resectable CCA patients who underwent surgical treatment in the First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021.The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed.A survival prediction model for patients with resectable CCA was constructed with COX regression results,the calibration curve and the time-dependent receiver operating characteristic curve(ROC)were used to evaluate the performance of the constructed model,and the predictive power between this model and the American Joint Committee on Cancer(AJCC)/TNM staging system(8th edition)was compared.Results:SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases.IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues.GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway,such as fatty acid metabolism,oxidative phosphorylation and amino acid metabolism.SIRT2 expression was related to serum triglycerides level,tumor size and lymph node metastasis(all P<0.05).The survival analysis results showed that patients with higher SIRT2 expression had a significantly lower overall survival(OS)than patients with lower SIRT2 expression(P<0.05).Univariate COX regression analysis suggested that pathological differentiation,clinical stage,postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients(all P<0.05).Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients(both P<0.05).A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed.The C-index of the model was 0.675,and the area under the time-dependent ROC curve(AUC)for predicting survival in the first,second,and third years was 0.879,0.778,and 0.953,respectively,which were superior to those of AJCC/TNM staging system(8th Edition).Conclusions:SIRT2 is highly expressed in CCA tissues,which is associated with poor prognosis in patients with resectable CCA.The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system(8th edition)in prediction of survival of postoperative CCA patients.


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