1.The Regulatory Role of Glucose Transporter 1 on the Function of Human Umbilical Vein Endothelial Cells Under Ischemia-hypoxic Conditions
Meiling LI ; Siqi GAO ; Zhefu LIU ; Huanyan LIAO ; Fanmao LIU ; Wenhao XIA ; Jun GUO ; Yan LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):444-455
Abstract: ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 (GLUT1) on the proliferation, migration, adhesion, and angiogenesis of human umbilical vein endothelial cells (HUVECs) under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment (1% O2, 5% CO2, 94% N2). The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability, proliferation capacity, and examining the expression changes of GLUT1, HIF-1α, and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further, GLUT1 was overexpressed using plasmid transfection and the proliferation, migration, adhesion, and angiogenic capabilities of HUVECs were evaluated through scratch assays, cell adhesion assays, and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy,and oxygen consumption rate (OCR) was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions, the ischemia-hypoxic environment significantly inhibited the proliferation, cell viability, migration, and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1, HIF-1α and VEGFA proteins were also markedly reduced. However, when GLUT1 expression was upregulated, the migration, adhesion, and angiogenic capabilities of HUVECs were significantly improved, and the protein expression levels of HIF-1α, VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage, while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions, potentially through modulating cellular energy metabolism and signal transduction pathways, thereby affecting cell proliferation, migration, adhesion, and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.
2.Current situation of healthcare-associated infection management of fever clinics in Wuhan medical institutions
Xiaoli LIU ; Lin GONG ; Yimei WANG ; Huiqiong XU ; Meiling LI ; Changfeng LI
Journal of Public Health and Preventive Medicine 2024;35(4):62-65
Objective To analyze the current situation of healthcare-associated infection (HCAI) management of fever clinics among different levels of medical institutions in Wuhan, and to provide a scientific basis for improving hospital infection management. Methods In January 2023, a network questionnaire survey was conducted on medical institutions with fever clinics in Wuhan. Results A total of 72 medical institutions were investigated, of which 58.33% had CT, and 48.61% had fever clinics for children. The total qualified rate of HCAI management was 78.28%. The qualified rates of four primary indicators, including hospital management, diagnosis and treatment environment protection, training and education, and implementation of infection control measures, were 82.27%, 71.49%, 75.93%, and 81.31%, respectively. There were statistical differences among different levels of medical institutions (all P<0.01). Among the 13 secondary indicators, the qualified rates of 7 indicators were more than 80%, with the highest being medical item management (93.06%), medical waste disposal (89.72%), and personnel management (83.33%), and the lowest being facilities and equipment (66.32%), and patients and accompanying personnel education (66.67%). Among the 65 tertiary indicators, 30 had a pass rate great than 80%. Conclusion Wuhan actively promotes the construction of fever clinics in medical institutions, and the overall situation of HCAI management is good. However, there are still some problems to varying degrees, especially in the layout procedures, hand hygiene, and staff training of fever clinics in secondary and lower medical institutions, which should be further strengthened.
3.Development and test of reliability and validity of the Visual Cognitive Ability Assessment Scale for Preschool Children
Na WANG ; Shuqing ZHOU ; Xiaojie GUO ; Xin ZHANG ; Xia CHI ; Xiling LI ; Meiling TONG
Chinese Journal of Child Health Care 2024;32(2):138-141
【Objective】 To develop the Visual Cognitive Ability Assessment Scale for Preschool Children and to evaluate its reliability and validity, in order to provide reference for clinical evaluation of visual cognitive ability of preschool children. 【Methods】 1) From November 2021 to February 2022, construct the dimension framework was constructed and the pool of scale items was compiled according to the theory. 2) In March to June 2022, items were screened preliminarily through group discussion and Delphi method. In August 2022, the entries was revised by a pre-survey in a small sample (n=50). 3) Parents of children aged 4 - 7 from 8 kindergartens in 4 main urban areas of Nanjing were investigated by stratified cluster random sampling method in September to December 2022. The valid sample of the first survey (n=344) was analyzed to conduct item analysis and re-test reliability analysis, the valid sample of the second survey (n=695) was tested for reliability and confirmatory factor analysis, then the scale was finally compiled and evaluated. 【Results】 1) The scale contained 19 items in 4 dimensions:visual memory, discerning vision, spatial vision and visual integration. All items passed the project analysis test. 2) The Cronbach′s α coefficient of each dimension ranged from 0.604 to 0.886, and the Cronbach′s α coefficient of the whole scale was 0.917. During the two surveys, the scores of each item were correlated, and the average retest reliability coefficient was 0.601 (P< 0.05). 3) Content validity index (S-CVI) at scale level was 0.91, and item level content validity index (I-CVI) ranged from 0.8 to 1.0. After several rounds of model modification, the confirmatory factor model fit well. 【Conclusion】 The reliability and validity of the Visual Cognitive Ability Assessment Scale for Preschool Children are acceptable and meet the requirements of the scale, which provides a practical tool for clinical screening of visual and cognitive disorders.
4.Explanation for the Methodological Framework for Interventional Clinical Research of Chinese Medicine under the Research Mode of Syndrome Dominating Disease
Qian HUANG ; Li ZHOU ; Meiling XUAN ; Xiaohui GUO ; Xingying QIU ; Bingqing LIU ; Wencong CAO ; Zehuai WEN
Journal of Traditional Chinese Medicine 2024;65(13):1328-1333
The methodological framework for interventional clinical research of Chinese medicine (CM) under the research mode of syndrome dominating disease provides a set of technical principles and methods to design, evaluate, and implement of this kind. It consists of three main parts including general principles, research points and key design elements, with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects, including basic norms to be followed in relevant studies, perspectives for selecting research topics, as well as the technological details on study population (P), intervention (I) and comparison(C), outcome measurement (O), time frame (T) of treatment and follow-up, sample orientation (prospective versus retrospective), study design (S) format and type. To provide practical guidance for future studies, this article clearly explains each items of the methodological framework through some supportive cases.
5.Evaluation of the efficacy and safety of phacoemulsification under the IOL protection: a randomized controlled clinical study
Yujiao JIN ; Nan LI ; Qiushuang SUN ; Weiyi JIN ; Meiling JIANG ; Yingfeng LIU ; Yan LU ; Lixia SUN ; Renzhe CUI
Chinese Journal of Experimental Ophthalmology 2024;42(3):248-255
Objective:To observe the therapeutic effect of intraocular lens (IOL) protected phacoemulsification (PHACO) in patients with hard nucleus cataract.Methods:A randomized controlled clinical study was conducted.A total of consecutive 120 patients (120 eyes) with hard nucleus cataract of Emery grade Ⅳ or Ⅴ were enrolled from January 2019 to May 2022.The patients were randomly divided into PHACO group receiving routine PHACO, IOL protected PHACO group receiving PHACO under IOL protection, and extracapsular cataract extraction (ECCE) group receiving ECCE, with 40 cases (40 eyes) in each group.Finally, 99 patients completed the follow-up, including 30 cases (30 eyes) in PHACO group, 35 cases (35 eyes) in IOL protected PHACO group, and 34 cases (34 eyes) in ECCE group.The total operation time, intraoperative PHACO time and cumulative energy release of each patient were recorded.The corneal endothelial cell density (ECD), coefficient of variation in endothelial cell area (CV), hexagonal endothelial cell ratio (6A), corneal astigmatism and the number of eyes with different grades of uncorrected visual acuity were measured and compared after 3-month follow-up.The intraoperative and postoperative complications were recorded.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Yanbian University Hospital (NO.2023002).Patients were informed of study content and purpose and signed a consent form before treatment.Results:There was no significant difference in ultrasonic energy and time between PHACO group and IOL protected PHACO group ( P=0.691, 0.982).The total operation time was (38.81±2.73) and (36.45±3.45) minutes in PHACO group and IOL protected PHACO group, significantly shorter than (69.60±4.35) minutes in ECCE group (both at P<0.001).There was no significant difference in age, sex, lens nucleus hardness and other baseline data among the three groups before operation (all at P>0.05).Three months after operation, the number of patients with higher uncorrected visual acuity in PHACO group and IOL protected PHACO group was larger than that in ECCE group ( P=0.006, 0.007).The ECD and 6A in IOL protected PHACO group were (2 155.57±177.88)/mm 2 and (41.31±5.18)%, respectively, which were significantly higher than (1 912.64±224.11)/mm 2 and (36.18±3.27)% in PHACO group, and the CV in IOL protected PHACO group was (50.34±5.90)%, which was lower than (55.67±3.30)% in PHACO group, showing statistically significant differences ( P=0.007, 0.003, 0.005).At 1 week and 3 months after the operation, the corneal astigmatism was significantly lower in IOL-protected PHACO group than in ECCE group, but higher than in PHACO group, and the difference were statistically significant (all at P<0.05). Conclusions:Compared with conventional PHACO, IOL-protected PHACO can effectively reduce the damage of corneal endothelium caused by ultrasonic energy, shorten the operation time and reduce postoperative inflammatory reaction compared with ECCE, and does not significantly increase postoperative corneal astigmatism.IOL-protected PHACO is an effective improved surgical method for patients with hard nucleus cataract.
6.Correlation Study on Serum RLP-C Level and TyG Index in Patients with Postmenopausal Type 2 Diabetes
Meiling YANG ; Benling HUANG ; Caixin LI
Journal of Modern Laboratory Medicine 2024;39(6):195-200
Objective To explore the correlation between serum residual lipoprotein cholesterol(RLP-C)and triglyceride glucose(TyG)index in postmenopausal type 2 diabetes(T2DM)patients.Methods A total of 389 postmenopausal T2DM patients who attended Ruili People's Hospital from May 2019 to May 2023 were included.RLP-C and TyG index were calculated,and the study subjects were divided into the low TyG index group(n=194)and the high TyG index group(n=195)based on the median of TyG index(9.23).Differences in general clinical data and metabolism-related indexes between the two groups of patients were compared,and Spearman rank correlation was performed to explore their correlation.Single-factor and multivariate Logistic regressions were used to explore their influencing factors,and ROC curve was used to analyze their diagnostic value.Results Compared with the low TyG index group,the history of hypertension(79.49%vs 70.62%),hyperlipidemia(22.05%vs 13.40%),hemoglobin(Hb)(120.34±19.96g/L vs 114.97±21.32g/L),fasting blood glucose(FBG)[3.97(3.03,5.10)mmol/L vs 3.64(2.99,4.74)mmol/L],total cholesterol(TC)[5.00(4.40,5.95)mmol/L vs 4.36(3.78,5.30)mmol/L],triacylglycerol(TG)[2.11(1.60,3.00)mmol/L vs 1.20(0.91,1.54)mmol/L],low-density lipoprotein(LDL-C)[[2.99(2.43,3.93)mmol/L vs 2.71(2.13,3.38)mmol/L],non-high-density lipoprotein(nonHDL-C)[3.94(3.22,4.82)mmol/L vs 3.15(2.53,3.94)mmol/L]and RLP-C concentration[0.76(0.52,1.08)mmol/L vs 0.44(0.29,0.59)mmol/L]of the high TyG index group were higher,while high-density lipoprotein(HDL-C)concentration was lower,and the differences were statistically significant(x2=4.09,4.99;t=-2.56;Z=-2.34,-5.15,-12.08,-3.04,-6.23,-9.15,-3.99,all P<0.05).Spearman correlation analysis showed that TyG in all samples was positively correlated with TC,TG,LDL-C,RLP-C and nonHDL-C(r=0.304,0.769,0.179,0.386,0.571,all P<0.001),but was negatively correlated with HDL-C(r=-0.306,P<0.001).The correlations between TyG and TC,LDL-C in the high TyG index group were not significant(all P>0.05).Single-actor logistic regression analysis showed that history of hypertension,hyperlipidemia,HDL-C,LDL-C,and RLP-C were the factors influencing TyG levels[OR(95%CI)=1.61(1.01~2.57),1.83(1.07~3.12),0.28(0.14~0.54),1.21(1.02~1.43),17.58(8.11~38.11),all P<0.05],while the multivariate regression analysis showed that only RLP-C was an independent risk factor for elevated TyG[OR(95%CI)=13.17(5.71~30.37),P<0.001).ROC curves showed that the AUC(95%CI)for the diagnosis of TyG index elevation by RLP-C was 0.768(95%CI:0.721~0.816),with the cutoffvalue of 0.59 mmol/L.The sensitivity and specificity were 69.71%and 75.77%,respectively.Conclusion RLP-C is an independent risk factor for elevated TyG in postmenopausal T2DM patients,which has some clinical value in predicting insulin resistance.
7.Application of whole exome sequencing in patients with primary ciliary dyskinesia
Ke CHEN ; Jing SHI ; Lijuan HU ; Li ZHANG ; Minlu CAO ; Wei GUO ; Meiling JIN
Chinese Journal of Clinical Medicine 2024;31(6):1006-1010
A 29-year-old man visited Zhongshan Hospital, Fudan University in December 2021. The patient presented with recurrent coughing, sputum, and wheezing, high level of serum total IgE, positive aspergillus fumigatus-specific IgE and extremely severe mixed ventilatory dysfunction. These features and thoracic CT results scan showed bronchiectasis and allergic bronchopulmonary aspergillosis. In consideration of his clinical characteristics, including low levels of fractional exhaled nitric oxide (FeNO), and nasal nitric oxide (nNO), persistent cough after birth, consanguineous marriage of his parents, etc. we ratiocinated a possibility of hereditary diseases, especially primary ciliary dyskinesia (PCD). From this perspective, whole exome sequencing (WES) was performed and the diagnosis of PCD was ultimately confirmed.
8.Mechanism of Wendan decoction in preventing obesity by regulating multiple signal pathway networks based on gene promoter methylation
Haiyan Yang ; Meiling Ren ; Ziting Wu ; Jinchao Li ; Ping Wang
Journal of Traditional Chinese Medical Sciences 2024;11(1):93-100
Objective:
To investigate the potential mechanism of Wendan decoction in obesity by screening target genes with promoter region methylation changes and constructing a multiple signaling pathways network based on promoter methylation.
Methods:
The methylation degree of Itgad, Col8a1, Adra2b, Jund, Rab2a, Wnt8b, Fzd9, B4galt7, Pik3cd, Creb1, Stard8, and Mmp1 in the abdominal adipose tissue of obese rats was determined using the Agena MassARRAY system. Western blot was performed to assess protein expression levels. Target genes were identified based on the methylation degree in the promoter region and protein expression. Enrichment analysis of signaling pathways was conducted to identify relevant target genes and obtain a multiple signaling pathway network associated with obesity. Core and terminal effector molecules in the pathway networks were selected as research targets for reverse transcription-polymerase chain reaction (RT-PCR) analysis.
Results:
Four genes (Adra2b, Creb1, Itgad, and Pik3cd) showed a degree of promoter methylation consistent with their respective protein expression levels. Among them, Adra2b, Creb1, and Pik3cd expression increased, while that of Itgad decreased. Enrichment analysis revealed that Creb1 and Pik3cd were involved in 6 signaling pathways related to obesity: tumor necrosis factor (TNF) signaling pathway, growth hormone synthesis/secretion and action, adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway, relaxin signaling pathway, cyclic nucleotide (cAMP) signaling pathway, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Subsequently, a multiple signaling pathways network was constructed based on promoter methylation. Key molecules including protein kinase B (AKT), mechanistic target of rapamycin complex 1 (mTORC1), and unc-51 like autophagy activating kinase 1 (ULK1), as well as terminal effector molecules interleukin-1β (IL-1β), interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 2 (CXCL2) were selected as research targets. Wendan decoction decreased the expressions of AKT, mTORC1, IL-1β, IL-6, and CXCL2 while up-regulating ULK1 expression.
Conclusion
The mechanism of Wendan decoction in preventing obesity involves the regulation of multiple signaling pathways through the control of Creb1 and Pik3cd gene promoter methylation. However, the associated multi-path gene regulation mechanism in preventing obesity is complex. Thus, further exploration is needed to elucidate the role of methylation changes in this mechanism.
9.Design,synthesis and biological activity evaluation of water-soluble borneol phosphate prodrug
Lulu ZHANG ; Meiling SUN ; Yajuan QIN ; Tingyou LI
Journal of China Pharmaceutical University 2024;55(3):375-380
In this study,structural optimization of borneol was carried out to improve their solubility and promote their further application in stroke therapy.BP-3,a prodrug of borneol,was designed and synthesized based on the principle of phosphate modification.The solubility of BP-3 was determined by evaporative light scattering detector(ELSD),and the degree and speed of drug release were tested in mouse plasma,and the neuroprotective effect of BP-3 was evaluated in mouse model of transient middle cerebral artery occlusion(tMCAO).According to the results,BP-3 was completely soluble in saline at 20 mg/mL;in mouse plasma,approximately 40%of the borneol were released within 2 h;in the tMCAO mouse model,TTC staining showed that BP-3 was effective in reducing the infarct area;Nissl staining showed that BP-3 ameliorated the neuronal injury;the grip and grasping strength tests elucidated that BP-3 reduced the damage of sports ability caused by injury;and the rotating rod test proved that BP-3 could promote the recovery of motor ability in mice.BP-3 has good water solubility,suitable drug release rate and excellent neuroprotective effects,and has broad prospects for drug development.
10.Clinicopathological features of pulmonary mucosa-associated lymphoid tissue lymphoma: analysis of 41 cases
Hui YANG ; Haijian HUANG ; Baicheng LI ; Meiling ZHENG ; Zaifeng LI ; Zhi YANG ; Xin CHEN ; Zhaohui LU
Journal of Leukemia & Lymphoma 2024;33(11):664-670
Objective:To investigate the clinicopathological features of pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma).Methods:A retrospective case series study was conducted. A total of 41 cases of pulmonary MALToma who were admitted to multiple centers from April 2002 to August 2023 were collected, including 33 cases from Fujian Provincial Hospital, 5 cases from Binzhou People's Hospital, 1 case from the Second Hospital of Zhangzhou, 1 case from the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, and 1 case from Jinjiang Hospital. The results of pathological morphological examination, immunohistochemical examination and genetic testing of patients were summarized, their clinicopathological characteristics were analyzed, and the relevant literature was reviewed.Results:Among the 41 patients, there were 24 males and 17 females, aged (58±13) years (range: 36-81 years). The longest diameter of the tumor under the gross macroscopic examination was (2.8±2.0) cm, with a range of 0.8-9.7 cm. Under the microscope, diffuse, flakelike and nodular patterns of lymphoid tissue were seen in the lung tissue with small- to medium-sized lymphoid cells including small lymphocytes, centrocyte-like cells, mononuclear cells and plasma cells. A small number of activated cells were noted, and the lymphoid cells grew along the alveoli. In some areas, the lymphoid cells invaded the bronchi, and lymphatic follicular implantation was rare; 1 case was accompanied by large cell transformation. Tumor cells expressed CD20, Pax-5, bcl-2, and CD43, with Ki-67 proliferation index of 2%-20%, and 50% in some areas of 1 case. The positive rate of clonal B-cell receptor gene rearrangement was 100.00% (29/29); the positive rate of MALT1 gene was 18.75% (3/16), and the positive rate of API2-MALT1 fusion was 66.67% (2/3). The treatment methods included surgery, anti-inflammatory therapy, radiotherapy, and chemotherapy. Follow-up for 4-143 months showed that 43.90% (18/41) had disease-free survival, 21.95% (9/41) had tumor bearing survival, 9.76% (4/41) died, and 24.39%, (10/41) were lost to follow-up. The progression-free survival of patients aged ≥ 60 years was worse than that of patients aged < 60 years ( χ2 = 5.39, P = 0.020). Conclusions:Pulmonary MALToma belongs to indolent B-cell lymphoma, and its diagnosis requires a combination of clinical imaging, pathology and immunophenotyping. If necessary, genetic testing can be used to assist in the diagnosis. The differential diagnosis should be made from pneumonia, low-grade B-cell lymphoma, and extrapulmonary MALToma with lung involvement. The treatment methods include anti-inflammatory therapy, surgical resection and chemotherapy, and the prognosis is good.


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