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.Intermittent hypoxia aggravates asthma inflammation via NLRP3/IL-1β-dependent pyroptosis mediated by HIF-1α signalling pathway.
Ling ZHOU ; Huojun ZHANG ; Lu LIU ; Fengqin ZHANG ; Lingling WANG ; Pengdou ZHENG ; Zhenyu MAO ; Xiaoyan ZHU ; Guisha ZI ; Lixiang CHEN ; Xiaojing CAI ; Huiguo LIU ; Wei LIU
Chinese Medical Journal 2025;138(14):1714-1729
BACKGROUND:
Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved.
METHODS:
A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro .
RESULTS:
In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation.
CONCLUSIONS
Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Humans
;
Asthma/metabolism*
;
Animals
;
Pyroptosis/physiology*
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Mice
;
Signal Transduction/physiology*
;
Male
;
Hypoxia/metabolism*
;
Female
;
Interleukin-1beta/metabolism*
;
Adult
;
Inflammation/metabolism*
;
Middle Aged
;
Mice, Inbred C57BL
4.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.
5.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.
6.Modified Xiaoyao powder for postpartum depression: A systematic review and meta-analysis
Mengyuan Hu ; Xiaowen Zhang ; Xuya Zhang ; Dan Cheng ; Yali Zhang ; Xinyu Zhang ; Lingling Li ; Xinjie Li ; Xue Li ; Yi Lu
Journal of Traditional Chinese Medical Sciences 2024;11(1):120-130
Objective:
To evaluate the effectiveness and safety of modified Xiaoyao powder for postpartum depression (PPD) by conducting a systematic review of randomized controlled trials (RCTs).
Methods:
The Chinese National Knowledge Infrastructure Databases (CNKI), the Chinese Scientific Journals Database (VIP), Wanfang, Google Scholar, the SinoMed, Embase, Cochrane Library, and PubMed databases were searched from their inception to April 25, 2023. The Cochrane Risk of Bias tool was used to assess the quality of the trials. We applied the risk ratio to present dichotomous data and the mean difference to present continuous data. Data with similar characteristics were pooled for meta-analysis and heterogeneity was assessed using I2.
Results:
This review included 35 trials involving 2848 participants. The quality of the included studies was low (unclear randomization processes and insufficient reporting of blinding). Participants treated with modified Xiaoyao powder plus Western medicine showed lower Hamilton Depression Scale (HAMD) depression score than those who used Western medicine alone (mean difference = −2.15; 95% confidence interval:−2.52 to 1.78; P < .00001), and higher effective rate (relative risk = 1.19; 95% confidence interval: 1.15 to 1.24; P < .00001), When comparing modified Xiaoyao alone with Western medicine, the HAMD depression score remained low, however, the efficacy rate was higher in the modified Xiaoyao group. Regarding adverse events, the modified Xiaoyao group reported weight gain, nausea, and diarrhea, but no severe adverse events were reported.
Conclusion
Modified Xiaoyao may help relieve depression in PPD when used alone or in combination with Western medicine, with minor side effects. Therefore, future high-quality, large-sample size RCTs are warranted.
7.Correlation of periodontitis with central nervous system inflammation in hypobaric hypoxia environments at plateau
Lu CHEN ; Xiaoxia JIANG ; Lingling ZHU
Chinese Journal of Comparative Medicine 2024;34(6):119-126
With the increase in human activity in plateau and mountainous areas in recent years,high-altitude exposure has become increasingly common.Many patients with underlying diseases are affected by hypobaric hypoxia in plateau environments,which further aggravates disease processes and even leads to cognitive disorders.Periodontitis is a common inflammatory disease that induces periodontal local inflammatory responses and even causes central nervous system inflammation.At high altitudes,the body suffers from decreased immunity and tissue hypoxia,which can promote the occurrence and development of periodontitis and may even increase the risk of periodontitis-induced central nervous system inflammation.As plateau medical research advances,the relationship between periodontitis and central nervous system inflammation in hypobaric hypoxia environments at plateau is attracting more and more attention.This work reviews the progress of research on periodontitis and central nervous system inflammation and discusses the correlation between periodontitis and central nervous system inflammation when exposed to hypobaric hypoxia in plateau environments.
8.Comparison of remazolam and midazolam for sedation of synchronous electrical cardioversion
Lingling CHEN ; Ren GUAN ; Muting LU ; Qiyin ZHANG
The Journal of Clinical Anesthesiology 2024;40(6):617-620
Objective To compare the sedative effect and safety of remimazolam and midazolam in synchronous electrical cardioversion in patients with atrial fibrillation.Methods Thirty-two patients with at-rial fibrillation receiving synchronous electrical cardioversion from January 2021 to December 2022 were en-rolled,22 males and 10 females,aged 18-80 years,BMI 20-30 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were randomly divided into two groups using random number table method:remimazolam group and midazolam group,16 patients in each group.The remimazolam group was sedated with 0.2 mg/kg of intra-venous remimazolam,and the midazolam group was sedated with 0.025 mg/kg of midazolam intravenously,and the drug injection time in both groups was 1 min.The anesthesia onset time,awakening time,and ori-entation recovery time were recorded.SBP,DBP,and SpO2 were recorded before anesthesia induction(T,),when the eyelash reflex was absent(T2),after the completion of electrical cardioversion(T3),and at the time of awakening(T4).Neurobehavioral cognitive state examination(NCSE)was performed 5 mi-nutes after the patients were awake,including language ability,structural ability,memory,calculation abil-ity and reasoning ability,and the pass rate of each ability test was calculated.The occurrence of adverse re-actions during surgery(body movement,apnea)and within 12 hours after surgery(nausea,vomiting,and chest pain)was recorded.Results Compared with the midazolam group,the anesthesia onset time,awak-ening time,and orientation recovery time in the remimazolam group were significantly shortened(P<0.05).There was no significant difference in SBP,DBP,and Sp02 between the two groups at different time points.Compared with the midazolam group,the pass rate of the reasoning ability test was higher in the remimazolam group 5 minutes after awakening(P<0.05).There was no significant difference in the inci-dence of adverse reactions between the two groups.Conclusion Compared with midazolam,remimazolam has faster onset of sedation,faster awakening,faster recovery of orientation in synchronous electrical cardio-version of atrial fibrillation,and faster recovery of reasoning ability in NCSE after synchronous electrical car-dioversion.
9.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.
10.Effects and mechanisms of 2.5T terahertz radiation exposure on testis injury in mice
Qinlong MA ; Min LIN ; Peng GAO ; Lingling YANG ; Yonghui LU ; Yanwen ZHANG ; Zhengping YU ; Chunhai CHEN
Journal of Army Medical University 2024;46(19):2197-2207
Objective To investigate the effects of terahertz(THz)radiation on mouse testicular tissue and its potential molecular mechanisms.Methods A total of 125 male C57BL/6J mice(6~8 weeks old)were randomly divided into control group and low-,medium-and high-radiation power groups.The mice of the latter 3 groups were exposed to THz radiation at a frequency of 2.5 T,with an average power density of 38,115,or 318 mW/cm2,for 5 or 10 min.The detection time was immediately or 24 h after exposure.HE staining was used to observe pathological damage.ELISA was employed to detect the expression of inflammatory factors in testicular tissue.RNA-seq was utilized to detect the global changes of gene expression.The differentially expressed genes(DEGs)were screened and bioinformatics was used to cluster them.The screened genes were further analyzed with RT-qPCR to determine the time-dependent and dose-dependent relationships of the expression with THz exposure.Finally,sperm quality was evaluated morphologically using a microscope.Results Three doses of THz radiation exposure did not cause significant pathological damages to mouse testicular tissue.TNF-α expression was increased immediately after exposure at average power density of 115 mW/cm2(P<0.01),and the expression of IL-1β and TNF-α were both increased when the dose reached 318 mW/cm2(P<0.01).However,all the 3 factors returned to normal levels in 24 h after exposure.RNA-seq results showed that THz radiation exposure caused abnormal expression of 56 genes.Cluster analysis indicated that these DEGs were mainly enriched in immune and inflammatory responses,enzyme activity,sperm development and capacitation functions.Then for 5 selected key genes,Crisp1,Adam7,Ltf,Rnase9,and Bsph1,the expression of Crisp1 and Rnase9 was decreased immediately after exposure to 115 mW/cm2 THz radiation,the dose of 318 mW/cm2 resulted in obvious changes in the expression of the 5 genes(P<0.05),and their expression returned to normal levels in 24 h after exposure.Morphological observation displayed that exposure to all the 3 doses of THz had no influence on sperm quality.Conclusion THz radiation exposure causes temporary inflammatory response in testicular tissue and abnormal expression of sperm functions-related genes.However,these changes return to normal 24 h after exposure,and additionally,do not impair sperm quality.


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