1.Porphyromonas gingivalis promotes autophagy in esophageal squamous cell carcinoma via the miR-21-5p/RASA1/ERK axis
Yubo DU ; Yelin JIAO ; Yueyue CHENG ; Haodong CHENG ; Yi RU ; Gaofeng LIANG ; Shegan GAO ; Yijun QI
Acta Universitatis Medicinalis Anhui 2024;59(9):1621-1628
Objective To investigate the molecular mechanism underlying Porphyromonas gingivalis(Pg)-induced autophagy in esophageal squamous cell carcinoma(ESCC).Methods After Pg infected KYSE70 cells and KYSE140 cells pretreated with siAtg7 or Chloroquin(CQ),Western blot was used to measure protein levels of Atg7,LC3-Ⅱ/LC3-Ⅰ,and p62;Immunofluorescent confocal imaging analysis was used to detect autophagosome and autolysosome;CCK-8 assay was used to test cell viability;Transwell assay was used for ESCC cell migration and invasion potentials.Likewise,miR-21-5p inhibitor,RASA1 overexpression plasmid,or U0126 were used to block miR-21-5p/RASA1/ERK signaling pathway prior to Pg infection,followed by the aforementioned methods.In addition,immunohistochemistry was used to examine Pg abundance and LC3 protein levels,and RT-PCR was used to evaluate miR-21-5p expression in ESCC and adjacent tissue samples,followed by correlation analyses be-tween Pg and LC3,and Pg and miR-21-5p.Results Pg infected KYSE70 cells and KYSE140 cells showed upreg-ulation Atg7 protein and LC3-Ⅱ/LC3-Ⅰ protein but downregulation of RASA1 protein and p62 protein,enhanced cell proliferation,migration,and invasion as well as immunofluorescent spots of red,green,and yellow in mRFP-GFP-LC3-labeled ESCC cells.Pretreatment with CQ or siAtg7 abolished the above alterations induced by Pg.Con-sistently,pretreatment with miR-21-5p inhibitor,U0126,or RASA1 overexpression plasmid also blocked Pg-stimu-lated autophagy.In ESCC samples,Pg abundance was correlated with upregulation of miR-21-5p and LC3.Con-clusion Pg promotes autophagy in esophageal squamous cell carcinoma via miR-21-5p/RASA1/ERK signaling pathway.
2.Correlation of sarcopenia and osteoporosis in postmenopausal elderly patients with type 2 diabetes
Ping ZHANG ; Yijun DU ; Yue WANG ; Yanqiu WANG ; Xiaoqun XU ; Tianrong PAN
Acta Universitatis Medicinalis Anhui 2024;59(10):1871-1874,1880
Objective To investigate the correlation between the appendicular skeletal mass index(ASMI)and os-teoporosis(OP)in postmenopausal patients with type 2 diabetes(T2DM).Methods 164 hospitalized postmeno-pausal elderly T2DM patients were selected and their bone density(BMD)and appendicular skeletal mass were measured using dual energy X-ray absorption method(DXA).ASMI=appendicular skeletal mass/height2(kg/m2),and they were divided into OP group and non OP group based on T value.The general clinical data,blood biochemical indicators,and ASMI between the two groups were compared,and Logistic regression analysis,ROC curve were further used to analyze the correlation and diagnostic power.Results Compared with non OP group,OP group had a higher incidence of sarcopenia(SAC)(P<0.05);the differences in age,ASMI,body mass index(BMI),and estradiol(E2)had significant differences between the two groups(P<0.05);Logistic regression analysis showed that the reduction of ASMI[OR=0.133,95%CI(0.029-0.611)],BMI[OR=0.785,95%CI(0.625-0.985)],and E2[OR=0.967,95%CI(0.942-0.993)]were protective factors for OP;receiver operating curve(ROC)suggested that the AUC of ASMI for OP prediction was 0.752[95%CI(0.632-0.872),P<0.001]with sensitivity 87.5%,specificity 47.8%,and the best diagnostic value was 5.52 kg/m2.Conclusion The reduction of ASMI,BMI,and E2 is positively correlated with the occurrence of osteoporosis.ASMI is an important protective factor for osteoporosis.Early OP screening and risk factor assessment should be conducted for elderly postmenopausal T2DM patients,and early intervention measures should be taken to reduce the risk of falls and fractures.
3.Renal cell carcinoma unclassified with medullary phenotype: a report of 2 cases and literature review
Yijun QIAN ; Xiaohua LIU ; Manming CAO ; Wei DU ; Kai GUO ; Yawen XU
Journal of Modern Urology 2024;29(12):1060-1063
[Objective] To investigate the clinical features and treatment of renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), so as to improve the clinical understanding of this disease. [Methods] The clinical data of 2 patients with pathological diagnosis of renal medullary carcinoma (RMC) in Zhujiang Hospital during 2019 and 2023 were retrospectively analyzed, and relevant literature was reviewed. [Results] Both patients had symptoms of backache, and imaging examination indicated renal space-occupying lesions.Case 1 was diagnosed as RMC by renal biopsy, and case 2 was pathologically diagnosed as RMC after surgery.Both cases lacked evidence of sickle cell trait or sickle cell disease, and were finally diagnosed as RCCU-MP.Case 1 did not receive antineoplastic therapy and died 5 months after diagnosis.Case 2 underwent laparoscopic nephrectomy, and then received gemcitabine + paclitaxel chemotherapy + immunotherapy.The patient's tumor progressed gradually after first-line treatment was abandoned due to concurrent hematologic infection, and he eventually died 7 months after surgery. [Conclusion] The clinical features of RCCU-MP are partially similar to those of RMC.The diagnosis of RCCU-MP requires pathological examinations and should exclude sickle cell trait or sickle cell disease.Due to the aggressive nature of the tumor, the prognosis of patients is poor.
4.Role and related mechanisms of LiaSR two-component system in acid tolerance and biofilm formation of Streptococcus mutans
Shan HUANG ; Jingyun DU ; Yijun LI ; Minjing WU ; Shuai CHEN ; Shan JIANG ; Xiaojing HUANG
Chinese Journal of Stomatology 2024;59(1):54-63
Objective:To investigate the role and related mechanisms of the LiaSR two-component system in acid tolerance and biofilm formation abilities of Streptococcus mutans (Sm) 593. Methods:The growth curves of various Sm strains in pH=5.5 brian heart infusion (BHI) medium were analyzed. And colony forming unit (CFU) was also performed to evaluate the acid tolerance of Sm. Laurdan probe, H +-K +adenosine triphosphate (ATP)ase activity analysis kit, proton permeability assay and real-time fluorescence quantitative PCR (RT-qPCR) were conducted to detect the acid tolerant mechanisms of LiaSR two-component system in Sm. Crystal violet staining, CFU, SYTOX probe and anthrone-sulfuric method were used to analyze the properties and structures of the Sm biofilms. RT-qPCR was conducted to detect the expression levels of underlying regulated genes. Results:The growth of mutants in acidic BHI were inhibited ( P<0.05). The acid tolerance of mutants significantly decreased compared to the wild-type strain ( P<0.05). In mutants, the activity of H +-ATPase (917.06±59.53 and 469.53±47.65) were elevated by 7.22-folds and 3.70-folds compared to the wild-type strain (127.00±50.71) ( P<0.001, P<0.001) and the encoded gene atpD (3.39±0.21 and 1.94±0.17) were also elevated by 3.39-folds and 1.94-folds compared to the wild-type strain (1.00±0.15) ( P<0.001, P=0.001). The Laurdan generalized polarization of mutants (0.18±0.04 and 0.18±0.05) increased significantly compared to the wild-type strain (0.08±0.05) ( P=0.006, P=0.003) and the expression levels of fabM gene were decreased in mutants (0.52±0.11 and 0.57±0.05) by 1/2 ( P=0.014, P=0.022). In liaR deletion mutant, the reduced terminal pH (4.76±0.01) can also be observed ( P<0.001). The total amount of the biofilms of three Sm didn't show significant differences ( P>0.05). But the number of viable bacteria of mutants′ biofilms were decreased [Sm 593: (12.00±2.80)×10 7 CFU/ml; Sm ΔliaS: (2.95±1.13)×10 7 CFU/ml; Sm ΔliaR: (7.25±1.60)×10 7 CFU/ml] ( P=0.001, P=0.024). The extracellular DNA were increased by 18.00-folds and 6.50-folds in mutants′ biofilms (128.73±15.65 and 46.38±5.52) compared to the wild-type strain (7.16±3.62) ( P<0.001, P=0.003). Water-soluble exopolysaccharides could be found up-regulated in liaS deletion mutant [(138.73±10.12) μg/ml] ( P=0.003) along with the expression level of gtfC gene (1.65±0.39) ( P=0.014). The expression level of gtfD were elevated by 47.43-folds and 16.90-folds in mutants ( P<0.001, P=0.010). Conclusions:The LiaSR two-component system can promote the expression of fabM gene and increase the fluidity of Sm which contributes to acid tolerance. The LiaR can also decrease the proton permeability and restrict the entrance of H +. The LiaSR two-component system can negatively regulate the production of the extracellular matrix in Sm biofilm.
5.Scalp acupunture can improve lower limb motor function and balance after a stroke
Yijun DU ; Juan HUAI ; Yonghui WANG ; Yujuan QU ; Wanlin LIU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(8):712-715
Objective:To observe any effect of dynamic scalp acupunture on the lower limb motor function and balance of stroke survivors.Methods:Eighty-two hemiplegic stroke survivors were randomly divided into a traditional scalp acupuncture group and a dynamic scalp acupuncture group, each of 41. In addition to routine symptom support treatment, the traditional scalp acupuncture group was given daily scalp acupuncture treatment and lower limb motor training 5 times a week for 3 consecutive weeks. The dynamic scalp acupuncture group was treated separately on the same schedule. Before and after the treatment, all were evaluated using the lower extremity part of the Fugl-Meyer motor function scale (FMA-LE), the Berg Balance Scale (BBS), the modified Barthel index (MBI) and functional ambulation categories (FAC).Results:Where was no significant difference between the two groups in any of the measurements before the treatment. Afterward the average FMA-LE, MBI and BBS scores of both groups had increased significantly, with greater improvement in the dynamic scalp acupuncture group. There was no significant difference in the two groups′ average functional ambulation categorization after the treatment.Conclusions:Dynamic scalp acupunture can effectively improve the lower limb motor function and balance of stroke survivors.
6.Optimizing visualization of thoracodorsal artery using energy spectrum CT angiography optimal single energy imaging combined with adaptive statistical iterative reconstruction V
Jian HE ; Yijun LIU ; Wei WEI ; Mengting HU ; Yong FAN ; Deshuo DONG ; Changyu DU
Chinese Journal of Interventional Imaging and Therapy 2024;21(10):613-617
Objective To observe the value of energy spectrum CT angiography(CTA)optimal single energy imaging combined with adaptive statistical iterative reconstruction V(ASIR-V)for optimizing visualization of thoracodorsal artery(TDA).Methods Energy spectrum CTA was prospectively performed in 60 patients to observe TDA.The images were reconstructed as 120 kVp-like combined with 40%post-set ASIR-V(group A),as well as totally 18 kinds of single energy images ranging from 45 to 70 keV(with interval of 5 keV)combined with 40%,60%and 80%post-set ASIR-V(group B),and the subjective and objective evaluation results of the images were compared between and within groups.Results Under the same post-set ASIR-V weight,significant differences of subjective scores of axial and 3D images were found among different keV levels(all P<0.001).With the increase of keV level,subjective scores of axial images increased first and then decreased,among which subjective score of 50 keV was the highest(all P<0.001).Under the same keV levels,with the increase of ASIR-V weight,the subjective scores of overall axial images and 3D images for displaying the main trunk of TDA,as well as contrast-to-noise ratio of axillary artery increased(all P<0.01).Conclusion Performing CTA using 50 keV single energy imaging combined with 80%ASIR-V reconstruction could balance image contrast and noise better,hence improving visualization of TDA and its branches.
7.Correlation analysis of anterior pituitary hormone and tumor size in patients with pituitary adenomas
Yuepeng WANG ; Yijun LI ; Bing LI ; Li ZANG ; Kang CHEN ; Jin DU ; Jingtao DOU ; Zhaohui LYU ; Weijun GU ; Yiming MU
Chinese Journal of Internal Medicine 2023;62(8):979-986
Objective:To summarize the correlation between anterior pituitary function and tumor size in patients with different hormone-secreting pituitary adenomas.Methods:This was a retrospective case series study. The clinical data of 1 946 patients with pituitary adenoma hospitalized in the First Medical Center of Chinese PLA General Hospital from January 1, 2005, to December 31, 2020, were collected. The correlation between tumor size and anterior pituitary hormone levels was analyzed using Spearman rank correlation analysis in different types of pituitary adenomas.Results:The median age of the 1 946 patients was 45.1 years, of which 857 (44.0%) were men. The maximum tumor diameter of the patients [ M ( Q1, Q3)] was 22 (14, 30) mm. Tumor size in nonfunctioning adenomas ( n=1 191) was negatively correlated with adrenocorticotropic hormone (ACTH) ( r=-0.11, P<0.001), growth hormone ( r=-0.13, P<0.001), and luteinizing hormone (men: r=-0.26, P<0.001, women: r=-0.31, all P<0.001). The tumor size of somatotropic adenomas ( n=297) was positively correlated with growth hormone ( r=0.46, P<0.001), but negatively correlated with male testosterone ( r=-0.41, P<0.001). The tumor size of ACTH-secreting pituitary adenomas ( n=155) was positively correlated with the ACTH level at 8∶00 AM ( r=0.25, P<0.001); however, no correlation was found with cortisol at 8∶00 AM ( P>0.05). The tumor size of prolactinomas ( n=303) was positively correlated with the prolactin level (men: r=0.34, P=0.001; women: r=0.13, P=0.070). Conclusions:The correlation between the function of the anterior pituitary and size of the tumor depends on the cellular origin of the pituitary adenoma and specific type of hormone secretion. In somatotroph adenomas, ACTH-secreting pituitary adenomas, and prolactinomas, there is a positive correlation between tumor size and level of hormones secreted by the corresponding tumors. In patients with nonfunctioning adenomas, the tumor size was negatively correlated with the hormone levels of the pituitary-adrenal and pituitary-growth hormone axes.
8.The effect of sodium-glucose co-transporter 2 inhibitor dapagliflozin on cognitive function in middle-aged and elderly patients with type 2 diabetes mellitus and related factors
Jingcheng DING ; Ying SUN ; Yanyun GUO ; Hong SU ; Yijun DU ; Tianrong PAN ; Xing ZHONG
Chinese Journal of Endocrinology and Metabolism 2023;39(9):772-777
Objective:To investigate the effect of dapagliflozin on cognitive function in middle-aged and elderly type 2 diabetes mellitus patients and related factors.Methods:This was a retrospective study. A total of 200 patients who were hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Anhui Medical University from August 2021 to August 2022 were recruited randomly. They were divided into the dapagliflozin group and control group. Clinical data were collected; plasma levels of β-amyloid protein(Aβ) 40 and Aβ42 were measured. The Montreal cognitive assessment(MoCA) and the mini-mental state examination(MMSE) were employed to assess cognitive function in both groups. Based on MoCA scores, patients in the dapagliflozin group were further categorized into mild cognitive impairment(MCI) and non-MCI subgroups. Differences among groups were analyzed and compared using t-test, χ2 test, and Mann-Whitney U test, and multivariable logistic regression was used to identify relevant factors associated with cognitive impairment in diabetes patients. Results:Compared to the control group, the dapagliflozin group exhibited significant increases in MMSE and MoCA scores, estimated glomerular filtration rate, and plasma concentration Aβ40(all P<0.05); And the incidence of MCI, homeostasis model assessment for insulin resistance(HOMA-IR), total cholesterol, triglycerides, urine albumin creatine ratio, plasma Aβ42, and Aβ42/Aβ40 ratio were significantly decreased(all P<0.05). Compared with the MCI subgroup, duration of dapagliflozin treatment in the non-MCI subgroup were significantly increased( P<0.05); There were statistically significant decreased in the non-MCI subgroup in age, systolic blood pressure, fasting plasma C-peptide, and HOMA-IR(all P<0.05). Multivariable logistic regression analysis showed that duration of dapagliflozin treatment was a protective factor for cognitive dysfunction( OR=0.322, 95% CI 0.150-0.692, P=0.004) and the age and HOMA-IR were risk factors( OR=1.109, 95% CI 1.014-1.212, P=0.023; OR=3.376, 95% CI 1.276-8.931, P=0.014). Conclusion:Dapagliflozin may improve cognitive function and significantly reduce the incidence of MCI in middle-aged and elderly patients with type 2 diabetes mellitus, possibly associated with the improvement of insulin resistance.
9.Protective effect of dulaglutide against sepsis⁃induced acute kidney inj ury in mice
Fengyi Deng ; Yue Wang ; Xingyu Fan ; Hujing Deng ; Xing Zhong ; Yijun Du ; Hong Su ; Tianrong Pan
Acta Universitatis Medicinalis Anhui 2023;58(8):1329-1334
Objective :
To investigate the protective effect of dulaglutide on acute kidney injury (AKI) induced by
lipopolysaccharide (LPS) .
Methods :
Twenty⁃four male C57BL/6 mice were randomly divided into Control group (normal saline) , LPS group (LPS 15 mg/kg) , LPS + Dul group (LPS 15 mg/kg + Dulaglutide 0. 6 mg/kg) and Dul group (Dulaglutide 0. 6 mg/kg) with 6 mice in each group. The drug was administered by intraperitoneal injection. After drug intervention for 24 h , the body weight and kidney weight of mice were recorded , and kidney tissue and serum samples were collected. The pathological changes in kidney tissue were observed by HE staining.
The serum urea nitrogen (BUN) and creatinine (CRE) levels were detected by the kit. The levels of cytokines interleukin (IL⁃6) , tumor necrosis factor (TNF⁃α ) and IL⁃1β in the kidney were detected by qRT⁃PCR. The contents of macrophage marker F4/80 and myeloperoxidase (MPO) in kidney were determined by immunohistochemistry.
Results :
Compared with Control group , mice in LPS group lost weight and increased kidney weight ( P <
0. 001) . Moreover, the levels of BUN and CRE increased (P < 0. 001 , P < 0. 01) . Meanwhile , the mRNA levels of IL⁃6 , IL⁃1β and TNF⁃α increased (P < 0. 05) . There was obvious pathological damage in kidney tissue. In addition , macrophage and neutrophil infiltration increased in LPS group ( P < 0. 001) . Compared with LPS group , mice in LPS + Dul group gained weight and lost kidney weight (P < 0. 05 , P < 0. 001) . Moreover, the levels of BUN and CRE in LPS + Dul group decreased (P < 0. 01) . The renal histological scores were reduced (P < 0. 05) . In addition , the levels of IL⁃6 , IL⁃1β and TNF⁃α in kidney tissue decreased (P < 0. 05 or P < 0. 01) . Moreover, the infiltration of macrophages and neutrophils in kidney was reduced (P < 0. 01) .
Conclusion
Dulaglutide has a protective effect on LPS⁃induced sepsis AKI , which may be related to reduce the expression of inflammatory media⁃ tors and decrease the infiltration of inflammatory cell.
10.Clinical characteristics of pituitary GH adenomas patients with different responses to oral glucose inhibitory GH test
Yuanyuan ZHAO ; Kang CHEN ; Jin DU ; Yijun LI ; Li ZANG ; Jianming BA ; Zhaohui LYU ; Jingtao DOU ; Yu PEI ; Weijun GU ; Qinghua GUO ; Yiming MU
Chinese Journal of Endocrinology and Metabolism 2022;38(4):294-299
Objective:To analyzed clinical characteristics of pituitary growth hormone(GH) adenomas patients with different responses to oral glucose inhibitory GH test.Methods:The clinical data of 50 patients with pituitary GH adenomas newly diagnosed with complete test data and case data in the Department of Endocrinology of Chinese PLA General Hospital was retrospectively analyzed from 2016 to 2021. The cases were divided into two groups according to the cutoff point of GH elevating to 50% of basaline during oral glucose test: abnormal elevation group(A group, n=16) and non-elevation group(B group, n=34). The clinical features, biochemistry, iconography, and immunohistochemistry of the two groups were analyzed. Results:The serum total cholesterol(TC)[(3.9±0.8) vs (4.6±0.9)mmol/L], 120 minutes insulin after glucose loading [11.2(4.4, 25.0) vs 92.0(10.8, 311.8)mU/L], long [1.0(0.4, 2.1) vs 1.5(0.5, 7.3) cm] and short[0.6(0.3, 1.3) vs 1.0(0.5, 5.8)cm] diameters of adenomas in A group were less than those in B group(all P<0.05) while insulin-like growth factor Ⅰ(IGF-Ⅰ) level was higher [(908.2±233.7) vs (743.1±273.1) ng/mL, P<0.05]. There were no significant differences in sex, age, disease course, clinical features, random GH, homeostasis model assessment of insulin resistance index(HOMA-IR), pituitary adenoma site, and invasive properties between the two groups. The immunohistochemical positive rates of ACTH(33% vs 0%) and prolactin(100% vs 28.6%)in A group were higher than those in B group( P<0.05). Conclusion:Pituitary GH adenomas patients with a paradoxical GH response pattern display lower serum TC and 120 minutes insulin levels as well as higher IGF-Ⅰ concentration and proportion of pituitary microadenomas. " Pure" growth hormone tumors may represent entities of a particular class of diseases in acromegaly.


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