1.Effect and Mechanism of TFAM on Chemotherapy Resistance in Ovarian Cancer Cells Through Metabolic Reprogramming Regulation
Lingling FAN ; Linglan LU ; Lili HAN
Cancer Research on Prevention and Treatment 2025;52(5):374-381
Objective To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells and its effects on metabolic reprogramming and sensitivity to platinum-based drugs Methods The mitochondrial function and metabolic characteristics of platinum-resistant ovarian cancer cells were analyzed. A TFAM-overexpressing cell model was established to assess its effects on platinum sensitivity, mitochondrial function, and aerobic glycolysis; and glycolytic enzyme and drug-resistant protein expression were analyzed. Results Platinum-resistant ovarian cancer cells exhibited considerable mitochondrial dysfunction (reduced oxygen consumption rate) and enhanced aerobic glycolysis (increased extracellular acidification rate, glucose uptake, and lactate production). TFAM was downregulated in resistant cells. Meanwhile, TFAM overexpression significantly enhanced platinum sensitivity (P<0.01), restored mitochondrial function, and inhibited aerobic glycolysis. The expression levels of glycolytic enzymes and drug-resistant proteins were also downregulated (P<0.05). Conclusion TFAM downregulation is associated with suppressed oxidative phosphorylation and enhanced aerobic glycolysis in platinum-resistant ovarian cancer cells. TFAM overexpression can restore cellular dependence on oxidative phosphorylation and increase platinum sensitivity, suggesting that TFAM is a potential therapeutic target for reversing platinum resistance.
2.Differentiation and treatment of urticarial vasculitis based on the theory of Xuanfu-collateral theory
Keyi LIU ; Ye TIAN ; Yue DU ; Ziye XI ; Haomin ZHANG ; Sisi LU ; Xin LI ; Lingling LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):542-546
Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.
3.Effect of modified Baduanjin exercise on cardiopulmonary function, motor function and activities of daily living for stroke patients
Junwen CHEN ; Qian CHEN ; Cheng CHEN ; Shuyue LI ; Lingling LIU ; Cunshu WU ; Xiang GONG ; Jun LU ; Guangxu XU
Chinese Journal of Rehabilitation Theory and Practice 2024;30(1):74-80
ObjectiveTo investigate the effect of modified Baduanjin exercise, as an rehabilitation exercise, on cardiopulmonary function, motor function and activities of daily living in patients with stroke. MethodsFrom January to September, 2023, 42 stroke patients in the Nanjing Qixia District Hospital were randomly divided into control group (n = 21) and experimental group (n = 21). The control group received routine rehabilitation, and the experimental group received modified Baduanjin exercise in addition, for four weeks. They were assessed with peak oxygen uptake (VO2peak), anaerobic threshold (AT), peak oxygen pulse (VO2peak/HR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), Fugl-Meyer Assessment-upper extremities (FMA-UE), Berg Balance Scale (BBS) and modified Barthel Index (MBI) before and after intervention. ResultsVO2peak, AT, and the scores of FMA-UE, BBS and MBI improved in the control group after intervention (|t| > 2.256, |Z| > 2.936, P < 0.05); while VO2peak, AT, VO2peak/HR, FVC, FEV1, PEF, and the scores of FMA-UE, BBS and MBI improved in the experimental group (|t| > 4.390, |Z| > 3.451, P < 0.001); and all the indexes were better in the experimental group than in the control group (|t| > 4.136,|Z| > 2.751,P < 0.01), except the scores of BBS and MBI. ConclusionModified Baduanjin exercise can improve the cardiopulmonary function and upper limb motor function for stroke patients.
4.Preoperative prediction of HER-2 expression status in breast cancer based on MRI radiomics model
Yun ZHANG ; Hao HUANG ; Liang YIN ; Zhixuan WANG ; Siyuan LU ; Xiaoxiao WANG ; Lingling XIANG ; Qing ZHANG ; Jiulou ZHANG ; Xiuhong SHAN
Chinese Journal of Oncology 2024;46(5):428-437
Objective:This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer.Methods:A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness.Results:The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model ( P<0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model ( P<0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort ( P<0.05) and was better than that of DCE-2 and ADC models in the validation cohort ( P<0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions:T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.
5.CiteSpace bibliometric analysis of safety and risk studies of antibody drugs in China
Yue PENG ; Lingling LIU ; Yuanxuan CAI ; Yuhang ZHAO ; Xiaofang SHANGGUAN ; Kangling LI ; Zherui CHEN ; Ke LI ; Rui HUANG ; Yuanyuan LU
China Pharmacist 2024;27(6):1019-1027
Objective To analyze the domestic antibody drug safety and risk research status,the latest research hotspots and frontiers in the current ten years.Methods CiteSpace 6.2.R2 software was used to analyze all literature related to the safety and risk of antibody drugs in CNKI,WanFang data and Vip database from 2012 to 2022.Results A total of 2 773 pieces of literature were obtained from the three databases,which were imported into CiteSpace after deduplication,and finally,1 870 pieces were included in the analysis.In the past decade,the number of articles published in the field of antibody drugs safety and risk research has remained at about 100 articles per year from 2012 to 2019,since 2020,the number of articles published has started to increase,and the annual number of articles published has increased to around 300 articles from 2021 to 2022.The network graph of domestic institutional cooperation showed that there was a lack of cooperation among the research institutions of antibody drug safety and risk research,mainly due to the fact that hospitals were conducting research in this field,and the types of research subjects were relatively single.The author collaboration network graph showed that the core teams in this research field,such as Li Bo,Yang Yanwei,and Lin Zhi,had the closest collaboration,while there was less collaboration among high-yield authors,additionally,some experts and scholars conducted research on their own as individuals or small groups,the research focused on adverse reactions,safety,bevacizumab,Rituximab,Meta-analysis,etc.Conclusion In the past decade,domestic research has mainly focused on the clinical efficacy and safety of antibody drugs,with few scholars exploring the risk of antibody drugs,therefore,in the future,it is necessary to pay attention to the research on the risks of antibody drugs.
6.Influencing factors for frailty among the elderly
JIN Lingling ; ZHANG Mingqing ; HUANG Chunyan ; FAN Wei ; WEI Xiaolin ; LU Yan
Journal of Preventive Medicine 2024;36(11):931-935
Objective:
To investigate the prevalence of frailty and its influencing factors among the elderly, so as to provide the evidence for prevention and control of frailty.
Methods:
The elderly population at ages of 65 years and older were selected from 14 administrative villages or communities in Wuzhong District, Suzhou City, Jiangsu Province, using the random cluster sample method from July to November, 2022. Demographic information, smoking and alcohol consumption were collected through questionnaire surveys. Physical activity, sleep quality and frailty were evaluated using the International Physical Activity Questionnaire-Short, Pittsburgh Sleep Quality Index and the FRAIL Scale, respectively. Factors affecting frailty among the elderly were evaluated using a multinomial logistic regression model.
Results:
A total of 8 782 elderly peolple were surveyed, including 4 259 males (48.50%) and 4 523 females (51.50%). The median age was 71.00 (interquartile range, 8.00) years. There were 2 145 cases with pre-frailty (24.42%) and 189 cases with frailty (2.15%). Multinomial logistic regression analysis showed that age (75-<85 years, OR=1.330, 95%CI: 1.186-1.492; ≥85 years, OR=2.452, 95%CI: 1.882-3.195), smoking (current smoking, OR=0.838, 95%CI: 0.714-0.983), physical activity level (low, OR=1.161, 95%CI: 1.010-1.333) and sleep quality (poor, OR=2.248, 95%CI: 1.822-2.774) were associated with pre-frailty; age (75-<85 years,OR=2.629, 95%CI: 1.921-3.596; ≥85 years, OR=3.067, 95%CI: 1.621-5.801), educational level (junior high school and above, OR=0.488, 95%CI: 0.298-0.798), body mass index (underweight, OR=1.848, 95%CI: 1.023-3.337; obesity, OR=1.798, 95%CI: 1.180-2.740), smoking (quit smoking, OR=1.787, 95%CI: 1.007-3.171; current smoking, OR=0.448, 95%CI: 0.242-0.830), alcohol consumption (yes, OR=0.532, 95%CI: 0.291-0.972), physical activity level (low, OR=2.757, 95%CI: 1.646-4.616) and sleep quality (poor, OR=3.911, 95%CI: 2.438-6.273) were associated with frailty.
Conclusion
Older, low physical activity level, poor sleep quality, underweight and obesity are associated with frailty of the elderly.
7.Parasitic leiomyoma of abdominal wall complicated with disseminated peritoneal leiomyomatosis:A case report and literature review
Jinping ZHANG ; Lingling TONG ; Lu GAO ; Hongjing CHENG ; Minjia SHENG
Journal of Jilin University(Medicine Edition) 2024;50(5):1432-1437
Objective:To discuss the diagnosis and treatment process of the patients with parasitic leiomyoma(PM)of the abdominal wall complicated with disseminated peritoneal leiomyomatosis(DPL)after laparoscopic myomectomy,and to improve the clinical understanding and management of this condition.Methods:The clinical data of one patient with PM of the abdominal wall complicated with DPL after laparoscopic myomectomy were collected.The causes,clinical features,diagnosis,differential diagnosis and treatment process were analyzed,and the relevant literatures were reviewed.Results:The patient,a 49-year-old woman,was admitted due to a self-discovered abdominal mass lasting for one year.The physical examination results showed a palpable mass,approximately 6 cm×4 cm,in the lower left abdominal wall with poor mobility,with clear borders,and without tenderness.Another palpable mass,approximately 7 cm×5 cm,was found in the lower right abdomen with fair mobility,with clear borders,and without tenderness.The gynecological ultrasonography results showed a hypoechoic area of approximately 6.6 cm × 2.7 cm in the subcutaneous tissue below the left umbilicus and another hypoechoic area of approximately 7.6 cm×3.3 cm in the abdominal cavity below the umbilicus.The superficial ultrasonography of the local area showed a hypoechoic area of approximately 5.79 cm× 2.55 cm×4.74 cm within the left lower abdominal rectus muscle,with smooth edges,located 1.97 cm from the skin at its shallowest point and 4.73 cm at its deepest point,without penetration of the rectus sheath but adjacent to the peritoneum.The patient was diagnosed as uterine leiomyoma,abdominal mass,and post-myomectomy status.The elective surgeries for uterine leiomyoma enucleation,abdominal wall leiomyoma excision,and peritoneal leiomyoma excision were performed under combined intravenous-inhalation anesthesia.The operation procedure was successful,and the patient recovered well and was discharged smoothly.Conclusion:PM and DPL lack typical clinical features and require imaging examinations for diagnosis.Surgical exploration is the main treatment modality,and while PM and DPL are generally benign,there is a potential for malignant transformation,and the patients need further postoperative follow-up.
8.Clinical value of neutrophil CD64 index in brucellosis
Zhiwei LI ; Qian WANG ; Lingling WANG ; Peipei LU ; Shuling LI ; Xiaoyu ZHU ; Jintong JIA ; Jie CHEN ; Changmin WANG
International Journal of Laboratory Medicine 2024;45(13):1541-1545
Objective To evaluate the clinical value of neutrophil CD64(nCD64)index as a novel biomark-er in the differential diagnosis of acute and chronic brucellosis.Methods A total of 38 patients with acute bru-cellosis and 48 patients with chronic brucellosis diagnosed in the People's Hospital of Xinjiang Uygur Autono-mous Region from February 2021 to July 2023 were included.Peripheral blood of the patients was collected and nCD64 index was detected by flow cytometry,and the correlation between nCD64 index and disease severi-ty was analyzed.Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and the specificity of nCD64 index in differentially diagnosing acute and chronic brucellosis.Meanwhile,Rose-Bengal Plate Test(RBPT)and Standard Tube Agglutination Test(SAT)were used as controls to evaluate the clini-cal diagnostic value of the three.Results The nCD64 index of acute brucellosis patients was higher than that of chronic brucellosis patients(U=216.00,P<0.001),and the index was positively correlated with the sever-ity of the disease(r=0.670,P<0.001).The ROC curve analysis results showed that the area under the curve of nCD64 index in the differential diagnosis of acute and chronic brucellosis was 0.882(95%CI:0.811-0.952,P<0.001),the cut-off value was 2.81,and sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 83.3%,81.6%,80.4%,81.9%and 82.6%,respectively.The efficacy of nCD64 index in differential diagnosis of nCD64 index was significantly better than those of the qualitative tests of RBPT and SAT.Conclusion nCD64 index has favourable sensitivity and specificity in the differential diag-nosis of acute and chronic brucellosis,and tends to reflect the severity of the disease.It has clinical value in the differential diagnosis of acute brucellosis and chronic brucellosis,and plays an important role in the early diag-nosis and treatment effect monitoring of brucellosis.
9.IL-33 mediates the immune regulation mechanism of brucellosis by regulating Treg cell function
Zhiwei LI ; Zaokeran·Aliken ; Lingling WANG ; Jintong JIA ; Shuling LI ; Xiaoyu ZHU ; Qian WANG ; Peipei LU ; Changmin WANG
International Journal of Laboratory Medicine 2024;45(18):2184-2188,2196
Objective To investigate the characteristics of changes in interleukin(IL)-33 and regulatory T(Treg)cells in brucellosis,to verify the regulatory effect of IL-33 on Treg cells,so as to clarify the immune mechanism of IL-33 on Treg cells in brucellosis.Methods The peripheral blood of 39 patients with brucellosis treated in the People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2021(the brucellosis group)and 42 healthy controls(the healthy control group)who underwent physical examination during the same period were collected.The serum IL-33 level was detected by AimPlex kit,and the proportion of Treg cells was detected by flow cytometry.Peripheral blood mononuclear cell(PBMC)was extracted and cultured in vitro to observe the proportion and mRNA expression levels of forkhead box protein P3(Foxp3)after stimulation and blocking of IL-33.Results Compared with the healthy control group,the level of IL-33 and the proportion of Treg cells in brucellosis group were significantly increased,with statistical significance(P<0.05).In vitro tests showed that the Foxp3 proportion and mRNA expression level of PBMC in the two groups were significantly increased after IL-33 stimulation,and significantly decreased after IL-33 blocking,with statistical significance(P<0.001).Conclusion IL-33 and Treg cells increased significantly in brucellosis patients,and IL-33 promoted the immune function of Treg cells.Blocking IL-33 is expected to be a potential target for immunotherapy of brucellosis.
10.Relationship between serum S100A11,S100A14,CA125 and cytoreductive surgery outcomes in patients with stage Ⅱ B-Ⅳ epithelial ovarian cancer and their predictive value
Hong LU ; Yi YIN ; Lingling LI ; Yong LI
International Journal of Laboratory Medicine 2024;45(19):2372-2376,2381
Objective To investigate the relationship between serum S100 calcium binding protein A(S100A)11,S100A14 and carbohydrate antigen 125(CA125)levels and the outcome of initial cytoreductive surgery in patients with stage Ⅱ B-Ⅳ epithelial ovarian cancer(EOC)and their predictive value.Methods A total of 124 patients with stage Ⅱ B-Ⅳ EOC who underwent initial cytoreductive surgery in the hospital from June 2018 to June 2021 were selected as the EOC group,70 patients with benign ovarian lesions were selected as the case control group,and 70 healthy people who underwent physical examination in the hospital during the same period were selected as the healthy control group.Serum levels of S100A11,S100A14 and CA125 were detected in each group.According to the outcome of cytoreductive surgery,EOC patients were divided in-to satisfactory group(70 cases)and unsatisfactory group(54 cases).The influencing factors of unsatisfactory surgical outcomes in patients with stage Ⅱ B-Ⅳ EOC were analyzed,and the clinical value of serum S100A11,S100A14 and CA125 in predicting unsatisfactory surgical outcomes in patients with stage Ⅱ B-ⅣEOC was evaluated.Results The serum levels of S100A11,S100A14 and CA125 in EOC group were higher than those in case control group and healthy control group(P<0.05).The proportions of American Society of Anesthesiologists(ASA)grade Ⅲ,ascites,International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC-Ⅳ and serum levels of CA125,S100A11 and S100A14 in unsatisfactory group were significantly higher than those in satisfactory group(P<0.05).FIGO stage 111 C-Ⅳ and elevated serum levels of CA125,S100A11 and S100A14 were independent risk factors affecting the unsatisfactory outcome of cytoreductive surgery in patients with EOC(P<0.05).The area under the curve(95%CI)of serum CA125,S100A11,S100A14 and the combination of the three to predict the unsatisfied outcome of EOC patients were 0.727(0.521-0.910),0.747(0.507-0.961),0.755(0.553-0.954)and 0.825(0.743-0.913),respectively.The predictive value of combined detection of CA125,S100A11 and S100A14 in predicting unsatisfactory outcome of cytoreductive surgery was better than that of serum CA125,S100A11 and S100A14 alone.Conclusion The el-evated serum levels of S100A11,S100A14 and CA125 in patients with stage ⅡB-Ⅳ EOC are associated with the unsatisfactory outcome of cytoreductive surgery.The combined detection of serum CA125,S100A11 and S100A14 has a high predictive value for the unsatisfactory outcome of cytoreductive surgery.


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