1.Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
Bin LIU ; Wen-Zhe DENG ; Wen-Hua HU ; Rong-Xi LU ; Qing-Yu ZHANG ; Chen-Feng GAO ; Xiao-Jie HUANG ; Wei-Guo LIAO ; Jin GAO ; Yang LIU ; Hiroshi KURIHARA ; Yi-Fang LI ; Xu-Hui ZHANG ; Yan-Ping WU ; Lei LIANG ; Rong-Rong HE
Acta Pharmaceutica Sinica B 2025;15(6):3149-3162
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.
2.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
3.Comparison of the efficacy of diquafosol sodium eye drops and cyclosporine eye drops in the treatment of dry eye after femtosecond laser small incision lenticule extraction
Jing DU ; Ning CAO ; Yan GAO ; Jia ZHANG ; Yuanyuan TIAN ; Yong LI ; Jing LI ; Juan LI ; Shengsh-Eng WEI ; Zhe YU ; Jinrong GAO
Recent Advances in Ophthalmology 2024;44(11):887-890,897
Objective To compare the efficacy of 30 g·L-1diquafosol sodium eye drops and 0.5 g·L-1 cyclospo-rine eye drops in patients with dry eye after femtosecond laser small incision lenticule extraction(SMILE).Methods A total of 37 patients(74 eyes)undergoing SMILE in Xi'an Fourth Hospital from January to February 2024 were selected as the subjects.Patients were randomly divided into the cyclosporine group(11 patients),diquafosol sodium group(16 pa-tients),and control group(10 patients)through a random number table method.There were no significant differences in the age and gender of patients in the three groups(both P>0.05).Patients in the cyclosporine group were treated with 0.5 g·L-1 cyclosporine eye drops,twice a day,1 drop each time,for 3 months.Patients in the diquafosol sodium group were treated with 30 g·L-1 diquafosol sodium eye drops,6 times a day,1 drop each time,for 3 months.Patients in the control group were treated with sodium hyaluronate eye drops,3 times a day,1 drop each time,for 3 months,and the fre-quency of administration could be adjusted according to clinical symptoms.The visual acuity,intraocular pressure,redness scan(R-Scan),Schirmer tear test(SIT),non-invasive break-up time(NIBUT)and ocular surface disease index(OSDI)questionnaire scores were measured in all patients at 1 month and 3 months after the operation.SPSS 22.0 statistical soft-ware was used for data analysis,and visual acuity,intraocular pressure,R-Scan,SIT,NIBUT and OSDI scores were com-pared among the three groups before,1 month and 3 months after the operation.Results In the cyclosporine group,in-traocular pressures of patients at 1 month and 3 months postoperatively were significantly lower than the preoperative level;the NIBUT was significantly prolonged at 3 months after operation compared with the preoperative level;OSDI scores were significantly elevated at both 1 month and 3 months postoperatively compared with the preoperative level(all P<0.05).In the diquafosol sodium group,intraocular pressure at 1 month and 3 months postoperatively was significantly lower than the preoperative level;the SIT at 3 months after the operation was lower than that before operation;OSDI was higher 1 month after operation than pre-operation and 3 months after operation(all P<0.05).In the control group,intraocular pressure at 1 month and 3 months postoperatively was significantly lower than the preoperative level;the naked eye visual acuity 3 months after operation was better than the best corrected visual acuity before operation(all P<0.05).There was no signif-icant difference in visual acuity,intraocular pressure and R-Scan among the three groups 1 month and 3 months after opera-tion(all P>0.05).One month after the operation,SIT and NIBUT in the control group were higher than those in the cy-closporine group and diquafosol sodium group(all P<0.05);the OSDI of diquafosol sodium group was higher than that of the cyclosporine group(P<0.05).Conclusion Both cyclosporine eye drops and diquafosol sodium eye drops can re-lieve ocular surface discomfort after SMILE and cyclosporine eye drops are more helpful to improve tear film stability.
4.Effect of artesunate on neuroinflammation in depressed mouse model by regulating cGAS-STING signaling pathway
Chao GAO ; Runhan ZHANG ; Wei WANG ; Manting ZHAO ; Yan JIAO ; Zhe LI
Basic & Clinical Medicine 2024;44(8):1126-1132
Objective To investigate the effect of artesunate(ART)on neuroinflammation in depressed mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon gene(STING)pathway.Methods Mice were divided into model group,control group,low-dose ART group,high-dose ART group,fluoxetine group,and high-dose ART+RocA(cGAS-STING pathway activator)group.Sugar solution consumption experiment and forced swimming experiment were applied to evaluate the depressive behavior of mice;HE staining microscopy was applied to detect pathological changes in hippocampal tissue;ELISA method was applied to detect the level of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),serotonin(5-HT)and dopa-mine(DA);TUNEL staining microscopy was applied to detect neuronal apoptosis;Western blot was applied to detect Bcl-2 associated X protein(Bax),p53,cGAS,and STING proteins.Results Compared to the control group,the mice in the model group exhibited neuronal pustule degeneration,the sugar water consumption rate,level of 5-HT and DA decreased,the rest time of forced swimming increased.The level of IL-6 and TNF-α,neuronal apoptosis rate,expression of Bax,p53,cGAS,and STING proteins all elevated(P<0.05);Compared with model group,the damage to hippocampus neurons in the ART low-dose group,ART high-dose group and fluoxetine group neuronal pus-tular degeneration was alleviated,while sugar water consumption rate,5-HT,and DA levels increased,the rest time of forced swimming reduced,the level of IL-6 and TNF-α,neuronal apoptosis rate and the expression of Bax,p53,cGAS,and STING proteins reduced(P<0.05);RocA reversed the improvement effect of high-dose ART on depression in mice.Conclusions ART inhibits neuroinflammation and neuronal apoptosis in depressed mice,and up-regulates amine neurotransmitters expression.The mechanism is potentially related to the blocking of cGAS-STING pathway.
5.Correlation between the level of NT-proBNP and cardiorespiratory fitness of individuals following acute high altitude exposure
Ping-Ping LI ; Xiao-Wei YE ; Jie YANG ; Zhe-Xue QIN ; Shi-Zhu BIAN ; Ji-Hang ZHANG ; Xu-Bin GAO ; Meng-Jia SUN ; Zhen LIU ; Hai-Lin LYU ; Qian-Yu JIA ; Yuan-Qi YANG ; Bing-Jie YANG ; Lan HUANG
Medical Journal of Chinese People's Liberation Army 2024;49(9):998-1003
Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.
6.Pathological evaluation of multiple intestinal segments and the macro-phage function study in hemorrhage rats
Hanqi WEI ; Jun MA ; Xingwei JIANG ; Yunqi SU ; Fenghua GAO ; Changwen NING ; Huaying AN ; Jiayuan GONG ; Pengyu LIU ; Zhe WANG ; Qun YU
Military Medical Sciences 2024;48(11):815-825
Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40%of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.
7.Treatment of Mitral bioprosthesis degeneration by transcatheter mitral valve-in-valve replacement via transseptal puncture:a case report
Zheng GAO ; Wei-Li LIU ; Zhan-Jun QU ; Qing-Zhe ZHAO ; Lei JIANG
Chinese Journal of Interventional Cardiology 2024;32(5):288-290
In recent years,the use of bioprosthetic mitral valves has been increasing,leading to a growing number of patients experiencing bioprosthesis degeneration,significantly impacting their quality of life.The high risk of reoperation has deprived many patients with mitral bioprosthesis degeneration of the opportunity for a second surgery.With the rapid development of interventional procedures in our country,transcatheter mitral valve-in-valve replacement is gradually being accepted by a large number of patients with bioprosthesis degeneration.We report a case of transcatheter mitral valve-in-valve replacement via transseptal puncture.The surgical plan was carefully formulated based on preoperative CT evaluation,and the patient underwent the procedure smoothly with no significant adverse events postoperatively.Transcatheter mitral valve-in-valve replacement may be a better alternative for patients at high risk of mitral bioprosthesis degeneration.
8.Obesity is positively Associated with Depression in Older Adults: Role of Systemic Inflammation.
Ye Xin GUO ; An Qi WANG ; Xin GAO ; Jun NA ; Wei ZHE ; Yi ZENG ; Jing Rui ZHANG ; Yuan Jing JIANG ; Fei YAN ; Mukaram YUNUS ; Hui WANG ; Zhao Xue YIN
Biomedical and Environmental Sciences 2023;36(6):481-489
OBJECTIVE:
We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults.
METHODS:
Adults ≥ 65 years old ( n = 1,973) were interviewed at baseline in 2018 and 1,459 were followed up in 2021. General and abdominal obesity were assessed, and serum C-reactive protein (CRP) levels were measured at baseline. Depression status was assessed at baseline and at follow-up. Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms, as well as the relationship between obesity and CRP levels. The associations of CRP levels with the geriatric depression scale, as well as with its three dimensions, were investigated using multiple linear regressions.
RESULTS:
General obesity was associated with worsening depression symptoms and incident depression, with an odds ratio ( OR) [95% confidence interval ( CI)] of 1.53 (1.13-2.12) and 1.80 (1.23-2.63), especially among old male subjects, with OR (95% CI) of 2.12 (1.25-3.58) and 2.24 (1.22-4.11), respectively; however, no significant relationship was observed between abdominal obesity and depression. In addition, general obesity was associated with high levels of CRP, with OR (95% CI) of 2.58 (1.75-3.81), especially in subjects free of depression at baseline, with OR (95% CI) of 3.15 (1.97-5.04), and CRP levels were positively correlated with a score of specific dimension (life satisfaction) of depression, P < 0.05.
CONCLUSION
General obesity, rather than abdominal obesity, was associated with worsening depressive symptoms and incident depression, which can be partly explained by the systemic inflammatory response, and the impact of obesity on depression should be taken more seriously in the older male population.
Humans
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Male
;
Aged
;
Depression/etiology*
;
C-Reactive Protein/metabolism*
;
Obesity, Abdominal/epidemiology*
;
Longitudinal Studies
;
Inflammation/epidemiology*
;
Obesity/complications*
9.Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome.
Xiao Li ZHANG ; Sheng Nan YU ; Ruo Di QU ; Qiu Yi ZHAO ; Wei Zhe PAN ; Xu Shen CHEN ; Qian ZHANG ; Yan LIU ; Jia LI ; Yi GAO ; Yi LYU ; Xiao Yan YAN ; Ben LI ; Xue Feng REN ; Yu Lan QIU
Biomedical and Environmental Sciences 2023;36(3):253-268
OBJECTIVE:
Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).
METHODS:
We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.
RESULTS:
Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome,featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.
CONCLUSION
Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats
;
Animals
;
Arsenic/toxicity*
;
Fluorides
;
RNA, Ribosomal, 16S/genetics*
;
Rats, Sprague-Dawley
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Metabolome
;
Microbiota
10.Effect of Calcified Lymph Nodes on Thoracoscopic Lobectomy in Chronic Obstructive Pulmonary Disease Patients with Lung Cancer.
Da-Wei WANG ; Fei YANG ; Ya-Zhe GUO ; Ya-Ying SU ; Xin LIU ; Yong-Shan GAO ; Zhen-Ming ZHANG
Acta Academiae Medicinae Sinicae 2023;45(1):33-37
Objective To observe the effect of calcified lymph nodes on video-assisted thoracoscopic surgery (VATS) lobectomy in the chronic obstructive pulmonary disease (COPD) patients with lung cancer. Methods A retrospective analysis was conducted on the COPD patients with lung cancer who underwent VATS lobectomy in the Department of Thoracic Surgery in the First Affiliated Hospital of Hebei North University from May 2014 to May 2018.The patients were assigned into a calcified lymph node group and a control group according to the presence or absence of calcified lymph nodes in CT,and the size,morphology,and calcification degree of the lymph nodes were recorded.The operation duration,intraoperative blood loss,chest tube retention time,hospitalization days,and overall complication rate were compared between the two groups. Results The 30 patients in the calcified lymph node group included 17 patients with one calcified lymph node and 13 patients with two or more calcified lymph nodes,and a total of 65 calcified lymph nodes were recorded.The calcified lymph nodes with the size ≤5 mm were the most common (53.8%),and complete calcification was the most common form (55.4%) in lymph node calcification.The mean operation duration had no significant difference between the calcified lymph node group and the control group (t=-1.357,P=0.180).The intraoperative blood loss (t=-2.646,P=0.010),chest tube retention time (t=-2.302,P=0.025),and hospitalization days (t=-2.274,P=0.027) in the calcified lymph node group were higher than those in the control group. Conclusion Calcified lymph nodes increase the difficulty and risk of VATS lobectomy in the COPD patients with lung cancer.The findings of this study are conducive to predicting the perioperative process of VATS lobectomy.
Humans
;
Blood Loss, Surgical
;
Retrospective Studies
;
Lung Neoplasms/surgery*
;
Pulmonary Disease, Chronic Obstructive
;
Calcinosis
;
Lymph Nodes

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