1.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
2.TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer.
Xiaoxia CHE ; Xin GUAN ; Yiyin RUAN ; Lifei SHEN ; Yuhong SHEN ; Hua LIU ; Chongying ZHU ; Tianyu ZHOU ; Yiwei WANG ; Weiwei FENG
Frontiers of Medicine 2025;19(1):121-133
Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans
;
Female
;
Ovarian Neoplasms/pathology*
;
Animals
;
Tripartite Motif Proteins/genetics*
;
Mice
;
Cyclin-Dependent Kinase 4/antagonists & inhibitors*
;
Cell Line, Tumor
;
Cyclin-Dependent Kinase 6/antagonists & inhibitors*
;
Protein Kinase Inhibitors/pharmacology*
;
Ubiquitin/metabolism*
;
Xenograft Model Antitumor Assays
;
Ubiquitination
;
Antineoplastic Agents/pharmacology*
3.Development countermeasures of internet medical service from the perspective of patient satisfaction
Lifei GU ; Huanquan PAN ; Tao YANG ; Kai ZHU
Modern Hospital 2024;24(3):431-433
Internet medical services provide a more convenient communication channel between doctors and patients.Doctors can communicate with patients through online consultation,telephone and other ways to understand the patient's condition and provide treatment suggestions.This kind of communication mode can enable patients to trust doctors more and establish a good doctor-patient relationship.Therefore,this paper analyzes the development of Internet medical services in hospitals,analyzes the development of services from the perspective of pre diagnosis,in-process and post diagnosis services,and puts forward countermeas-ures for the development of Internet medical services from the perspective of patient satisfaction in view of the lack of perfect policy guarantees,the inability to effectively feedback the needs of patients,the lack of mature service models and other issues.
4.Meta-synthesis of qualitative researches on the caring experience of caregivers of lung transplantation patients
Haiqing ZHOU ; Jing XU ; Xiaoli LI ; He LIU ; Lei LIU ; Minghua ZHANG ; Lifei SHI ; Enxia ZHU ; Ruting GU
Chinese Journal of Modern Nursing 2024;30(17):2280-2287
Objective:To systematically review and integrate the caring experience of caregivers of lung transplant patients.Methods:Qualitative studies on the caregiving experience of caregivers of lung transplant patients were searched by computer from PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang data, and the search period was from establishment of the databases to April 30, 2023. The qualitative research quality evaluation criteria (2016 edition) of the Joanna Briggs Institute Evidence Based Health Care Center in Australia were used to evaluate the quality of the included literature, and the Meta-synthesis was used to integrate the literature results.Results:A total of ten articles were included, and 33 clear research results were extracted, which were summarized into eight new categories, and finally summarized into four integrated results, such as heavy burden experience, strong demand, positive experience and satisfaction with the medical service system.Conclusions:Medical workers should attach importance to and pay attention to the burden and needs of caregivers of lung transplant patients, provide professional and emotional support to caregivers, improve their caring ability and quality, and ultimately improve the quality of life of lung transplant patients.
5.Early developmental levels of children with autism spectrum disorder with different adaptive behaviors: a retrospective analysis.
Chao SONG ; Ting HAN ; Lifei HU ; Ning SHAO ; Zepeng WANG ; Yan JIN ; Tingting CHEN ; Zhiwei ZHU
Journal of Zhejiang University. Science. B 2024;25(11):1031-1038
The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) (American Psychiatric Association, 2013) defines autism spectrum disorder (ASD) as a complex neurodevelopmental disorder that begins in early childhood and is accompanied by social communication deficits and repetitive stereotyped behaviors. According to the monitoring data released in 2021 in the United States, the prevalence of ASD in children was as high as 2.27%; that is, one in 44 children had autism (Maenneret al., 2021). China publicly reported this figure to be around 0.7% (Zhou et al., 2020). The current view is that children with ASD are generally impaired in their adaptation ability (McDonaldet al., 2016; Hodgeet al., 2021; Opertoet al., 2021). Adaptive behaviors comprise the conceptual, social, and practical skills that enable individuals to adapt to the environment, which play an important role in daily life (McDonald et al., 2019). "Adaptive behavior" was first described by Doll (1936). Subsequently, abnormalities in adaptive behavior were included in the criteria for intellectual disability for the first time (Heber, 1961). The American Association on Mental Retardation (AAMR) has refined and specified this term several times. Researchers hold different opinions on the structure of social adaptive capability. Greenspan and Granfield (1992) divided social adaptive capability into social understanding and social interaction. However, an increasing number of scholars considered that the concept of adaptive behaviors in children was constructed via multiple dimensions. The most representative one among them was the Vineland Adaptive Behavior Scales (VABS) proposed by Sparrow et al. (1984). This scale illustrates that adaptive behavior includes communication, daily living skills, socialization, and motor skills. Harrison and Oakland (2003) developed an Adaptive Behavior Assessment System (ABAS), by applying the theory of adaptive behavior proposed by AAMR and the American Association on Intellectual and Developmental Disabilities (AAIDD). This system shows that adaptive behavior has three adaptive composites, namely, conceptual composite (including communication, learning function, and self-management), social composite (including leisure and social skills), and practical composite (including community application, home living, health and safety, and self-care). As there are different requirements for the social adaptive capability of children from different cultural backgrounds and various regions, Chinese scholars have translated the Normal Development of Social Skills from Infant to Junior High School Children (S-M) scale compiled by Japanese scholars into Chinese, which is now widely used in China (Zhang et al., 1995). The impairment of adaptive function in children with ASD includes multiple dimensions, such as socialization, communication, and daily living skills (Kanne et al., 2011), and the degree of impairment can predict the prognosis and outcome in real life, including education acquisition and independent living ability (Farley et al., 2009). Therefore, adaptive behavioral capacity is considered to be a key intervention point that directly affects the individual and social outcomes of autistic children (Veenstra-VanderWeele et al., 2017; Bölte et al., 2019).
Humans
;
Autism Spectrum Disorder/psychology*
;
Male
;
Adaptation, Psychological
;
Child, Preschool
;
Female
;
Child
;
Retrospective Studies
;
China/epidemiology*
6.Construction of a risk prediction model for poor healing of surgical incisions after removal of thoracic and abdominal drainage tubes
Haiqing ZHOU ; Mingxue WANG ; Chunye WANG ; Enxia ZHU ; He LIU ; Lifei SHI ; Xiumei CHU
Chinese Journal of Modern Nursing 2022;28(1):70-75
Objective:To explore the independent risk factors of poor healing of surgical incisions in patients with drainage tube removal after thoracic and abdominal surgery and establish a risk prediction model for poor healing of surgical incisions.Methods:Using the convenient sampling method, a total of 545 patients who underwent thoracic and abdominal surgery in the Affiliated Hospital of Qingdao University were selected from July to December 2020. The patients were divided into the poor wound healing group ( n=87) and the non-incision poor healing group ( n=458) according to whether they had poor wound healing. Logistic regression analysis was used to analyze the risk factors of poor healing of surgical incisions and build a risk prediction model. The receiver operating characteristic (ROC) area under the curve was used to test the model to predict the effect and 230 patients were selected to verify the model prediction effect. Results:In this study, 5 factors including duration of exudation, serum albumin, incision infection, the volume of exudation during catheterization and catheterization time were finally included to construct a risk prediction model. The model formula was Z=4.608+4.855× duration of exudation +3.173× serum albumin +3.739× infection of the incision +2.271×the volume of exudation during catheterization + 0.466× catheterization time. The area under ROC curve of this model was 0.773 (95% CI: 0.678 - 0.868). The maximum value of Youden index was 0.549, the sensitivity was 0.742 and the specificity was 0.807. Conclusions:The risk prediction model of poor incision healing after drainage tube removal for patients undergoing thoracic and abdominal surgery can better predict the risk of poor incision healing and provide a basis for clinical medical staff to take preventive management measures for high-risk patients in time.
7.Preliminary experience of robotic-assisted laparoscopic surgery for bladder rhabdomyosarcoma in children
Pin LI ; Huixia ZHOU ; Hualin CAO ; Tao GUO ; Weiwei ZHU ; Yang ZHAO ; Tian TAO ; Xiaoguang ZHOU ; Lifei MA
Chinese Journal of Urology 2020;41(11):856-860
Objective:To evaluate the safety and feasibility of robotic-assisted laparoscopic resection of bladder rhabdomyosarcoma.Methods:A retrospective study was performed in 4 children underwent robotic-assisted surgery for bladder rhabdomyosarcoma from July 2018 to September 2019 in our hospital. The perioperative information and short time outcomes were collected. All the four patients were male. The average age of these patients was 68 months (from 11 to 122 months). After cystoscopy biopsy was conducted, preoperative chemotherapy was carried out. Preoperative radiotherapy was also added depends on the tumor response, then robotic-assisted surgery was performed. Radical cystectomy and orthotopic neobladder reconstruction with bilateral ureter reimplanataion were carried out for the bladder was widely occupied case. Bladder preserving surgery was performed for the other three localized cases.Results:All of the four operations have been conducted successfully without conservation to open surgery. The mean operative time was 189(104-316) min while the mean estimated blood loss was 32.5(20-50) ml. The mean tumor diameter was 4.48(2.7-6.0)cm. According to the pathological results, all of the four cases were diagnosed as embryonal rhabdomyosarcoma. One case had positive margin while other three cases had negative margins. No complication more than Clavien-Dindo grade Ⅲ was observed. The mean length of hospital stay was 18(14-24)days and the mean follow-up time was 14.7(7-21) months. Postoperative chemotherapy was carried out according to the protocol of IRS low risk group for all cases (VAC, eight cycles). Postoperative radiotherapy was conducted for the case with positive margin. No recurrence was recorded during the follow-up period.Conclusions:Robotic-assisted laparoscopic technique for the treatment of bladder rhabdomyosarcoma in children is safe and feasible.
8.Medical and interventional approaches to acute management of spontaneous intracerebral hemorrhage
Chinese Journal of Neurology 2020;53(9):715-720
Spontaneous intracerebral hemorrhage (ICH) continues to be associated with the highest mortality and morbidity of all forms of stroke. Early identification and management of ICH is crucial. Blood pressure control, care in a dedicated stroke unit, identification of secondary etiologies, reversal of associated coagulopathy, and neurosurgical management, when indicated, are essential to optimizing outcomes.
9. Interpretation in the update of Chinese guidelines for diagnosis and treatment of acute intracerebral hemorrhage 2019
Chinese Journal of Neurology 2019;52(12):985-988
Great improvements have been made in diagnosis and treatment of intracerebral hemorrhage in recent years. Chinese guidelines for diagnosis and treatment of intracerebral hemorrhage 2019 are published by Chinese Society of Neurology and Chinese Stroke Society in this issue of
10. Clinical value of echocardiography in differential diagnosis of segmental wall motion abnormalities in coronary heart disease
Qixun MAO ; Lifei SHAO ; Yang LIU ; Wen ZHU
Chinese Journal of Primary Medicine and Pharmacy 2019;26(15):1838-1841
Objective:
To explore the clinical value of echocardiography in differential diagnosis of segmental wall motion abnormalities in coronary heart disease(CHD), and to provide help for clinical treatment.
Methods:
From January 2017 to November 2018, 56 patients with segmental abnormal wall motion of CHD in Yuyao People's Hospital of Zhejiang Province were selected in the study.All patients were diagnosed by echocardiography and coronary angiography.The diagnostic coincidence rate, specificity, sensitivity, false negative rate, false positive rate and accuracy of echocardiography were evaluated.
Results:
Coronary angiography showed abnormal segmental wall motion in 56 patients, with 100.00% anastomosis rate.Echocardiography revealed abnormal segmental wall motion in 54 patients with CHD, 2 patients showed normal segmental wall motion, anastomosis rate was 96.43%.There was no statistically significant difference between the two diagnostic methods(χ2=0.635,


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