1.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
2.Efficacy of levodopa and benserazide combined with pramipexole on patients with Parkinson's disease and its influence on cognitive function and oxidative stress indicators
Jianping PAN ; Yun ZHANG ; Wenyu TANG ; Xuan MA
Clinical Medicine of China 2024;40(5):357-363
Objective:To investigate the effect of levodopa and benserazide combined with pramipexole in the treatment of Parkinson's disease (PD) and its influence on cognitive function and oxidative stress indicators.Methods:From January 2021 to December 2023, the clinical datas of 110 PD patients in the Neurocritical Rehabilitation Center of Xi'an International Medical Center Hospital were selected for a prospective study. Based on the principle of balanced and comparable baseline features between groups, they were divided into single drug group (odd number, 55 cases, oral levodopa and benserazide, effective dose: 500-1 000 mg/d) and combined group (even number, 55 cases, pramipexole based on single drug group, effective dose: 0.375-4.500 mg/d) according to the simplified randomization method (odd-even number method). The therapeutic effect (Unified Parkinson's Disease Rating Scale (UPDRS)), improvement status of symptoms, cognitive ability (Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA)), oxidative stress indicators (superoxide dismutase (SOD), malondialdehyde) and brain injury indicators (central nervous system specific protein β (S100β), human Parkinson protein 7 (PARK7)) before and after treatment and adverse drug reactions were compared between groups of patients.Results:After treatment, the scores of UPDRS Ⅰ, Ⅱ and Ⅲ dimensions in the two groups were significantly decreased, and the above scores with ((5.53±1.16, 20.43±3.98, 14.37±3.07) points) in combined group were significantly lower than ((7.06±1.64, 24.56±4.37, 17.32±3.83) points) in single drug group ( t values were 5.65, 5.18 and 4.46, respectively; all P<0.001). After treatment, the autonomic disorder and sensory disturbance were significantly improved in both groups, but the proportion of sensory disturbance after treatment in combined group (20.00%, 11/55) was significantly lower than that in single drug group (38.18%, 21/55), and the difference was statistically significant ( χ2=4.41, P=0.036). The MMSE score in the two groups after treatment was decreased significantly while the MoCA score was increased significantly, but the MMSE score in combined group with ((10.38±1.95) points) was significantly lower than ((12.27±2.26) points) in single drug group. The difference was statistically significant ( t=4.70, P<0.001) while the MoCA score with ((18.46±3.21) points) was significantly higher compared with ((16.84±3.07) points) in single drug group.The difference was statistically significant ( t=2.71, P=0.008). After treatment, SOD in the two groups was risen significantly while malondialdehyde was declined significantly, and SOD in combined group with ((82.53±10.63) U/L) was significantly higher than ((76.54±8.85) U/L) in single drug group, while malondialdehyde with ((4.64±0.85) μmol/L) was significantly lower than ((6.46±1.26) μmol/L) in single drug group. The difference is statistically significant ( t values were 3.21 and 8.88, respectively; P values were 0.002 and <0.001). The levels of S100β and PARK7 in both groups were reduced significantly after treatment, and the combined group ((73.64±5.72) ng/L, (78.04±6.93) μmol/L) had significantly lower levels than the single drug group ((15.73±3.25) ng/L, (22.23±3.84) μmol/L). The differences were statistically significant ( t-values were 3.63 and 9.58, respectively; both P<0.001). There was no statistical difference in incidence of adverse drug reactions between groups ( P>0.05). Conclusion:Levodopa and benserazide combined with pramipexole can enhance the cognitive function of PD patients and improve the oxidative stress indicators, with few adverse reactions, safe and effective, and is worthy of application.
3.Clinical study of acupuncture comnined with robot training on the balance function of Parkinson's disease
Zhiqing CHENG ; Lulu PAN ; Sujin LIN ; Wenyu CHEN ; Yinghao ZHI
China Modern Doctor 2023;61(35):9-12,41
Objective To investigate the therapeutic effect of different combinations of acupuncture and robot training on balance function in patients with Parkinson's disease.Methods A total of 60 patients with Parkinson's disease admitted to Wenzhou Traditional Medicine Hospital from October 2020 to October 2022 were randomly divided into two groups.Group A was given robot training after receiving acupuncture of Baihui and Dazhui points.Group B received those treatments simultaneously.And the balance function of patients was evaluated by Berg balance scale(BBS),Morse fall assessment scale(MFS)and timed up and go test(TUGT).Results In the intra-group comparison,TUGT in group A was significantly improved after 4 weeks of treatment(P<0.01);MFS and TUGT in group B were significantly improved compared with those before treatment(P<0.01).After 8 weeks of treatment,BBS and TUGT in group A were significantly improved compared with those before treatment(P<0.01);BBS,MFS and TUGT in group B were significantly improved compared with those before treatment(P<0.01).At the 12th week,BBS,MFS and TUGT in both groups were significantly improved compared with those before treatment(P<0.01).Comparison between groups:BBS,MFS and TUGT in group B were not significantly different from those in group A at 4 weeks of treatment(P>0.05);After 8 weeks of treatment,MFS in group B was significantly improved compared with that in group A(P<0.05),BBS and TUGT were better than that in group A without significant difference(P>0.05).After 12 weeks of treatment,BBS(P<0.01),MFS(P<0.01)and TUGT(P<0.05)in group B were significantly improved compared with group A.Conclusion Acupuncture at Baihui and Dazhui points combined with robot training simultaneously can improve the balance function and anti-falling ability of Parkinson's disease.
4.Anti-Seizure and Neuronal Protective Effects of Irisin in Kainic Acid-Induced Chronic Epilepsy Model with Spontaneous Seizures.
Jie YU ; Yao CHENG ; Yaru CUI ; Yujie ZHAI ; Wenshen ZHANG ; Mengdi ZHANG ; Wenyu XIN ; Jia LIANG ; Xiaohong PAN ; Qiaoyun WANG ; Hongliu SUN
Neuroscience Bulletin 2022;38(11):1347-1364
An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
Rats
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Animals
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Kainic Acid/toxicity*
;
Brain-Derived Neurotrophic Factor/metabolism*
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Fibronectins/metabolism*
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Hippocampus/metabolism*
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Rats, Sprague-Dawley
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Epilepsy/metabolism*
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Seizures/prevention & control*
5.The epidemiological characteristics and clinical diagnosis and treatment of 43 cases of novel coronavirus pneumonia
Jian ZHANG ; Yunhong ZHAO ; Yingxin HUANG ; Lina FENG ; Fei TENG ; Ying ZHANG ; Weina PAN ; Wenyu CUI
Chinese Journal of Experimental and Clinical Virology 2020;34(6):578-581
Objective:To retrospectively analyze the epidemiological and clinical characteristics of novel coronavirus pneumonia (COVID-19), and to provide evidence for its further prevention and control.Methods:The epidemiological history, clinical symptoms, pulmonary CT changes, treatment plan (hormone intervention or not), and negative conversion time of nucleic acid were summarized and analyzed in 43 COVID-19 patients.Results:All the 43 patients had clear contact history, among which the number of patients transmitted from conference microphone was the largest (13 cases). There were 2 cases of critical disease, 4 cases of severe disease and 37 cases of common type. The main symptoms were fever (30 cases, 69.8%) and cough (40 cases, 72.1%). Lung CT mainly showed single or multiple ground glass shadows (40 cases), which were all absorbed by the treated lesions, among which 28 cases had a transient aggravation of the lesions during the treatment. All the 43 cases were treated with integrated traditional Chinese and western medicine, 2 cases in critical condition were treated with non-invasive ventilator, and 19 cases were treated with low-dose hormone. The average nucleic acid negative conversion time was 13.28 days, and the use of hormones had no significant effect on the negative conversion time ( P>0.05). Conclusions:COVID-19 of common type is the commonest. Early respiratory support therapy is recommended for critical cases. Hormone intervention makes no obvious influence on the negative conversion time of nucleic acid. Close contact in a closed environment greatly increases the risk of transmission.
6.The status of psychological capital and its correlation with job burnout in ICU nurses
Weixing LI ; Mingyan ZHAO ; Suozhu YANG ; Daozhuo PAN ; Wenyu SONG ; Xu HAN
Chinese Journal of Modern Nursing 2019;25(15):1930-1932
Objective? To explore the status of psychological capital of ICU nurses and the correlation between nurses' psychological capital and job burnout, so as to provide the guidance for nursing managers in the management work. Methods? Convenience sampling method was used to select 200 ICU nurses in 4 ClassⅢGrade A Hospitals in Harbin as study subjects. The Nurses' Job Burnout Scale (NBS) and Psychological Capital Scale were used in the study to evaluate the correlation between psychological capital and job burnout. Results? A total of 187 valid questionnaires were collected. The score of Psychological Capital Scale of ICU nurses was (88.38±7.26), the average score of items was (3.68±0.71) , the score of hopefulness was (4.02±0.78) , self-efficacy was (3.84±0.67), flexible anti-resistance was (3.66±0.54) and optimistic was (3.21±0.86). There was a negative correlation between the total score and each dimensional score of ICU nurses Psychological Stress Scale and the scores of NBS including all dimensions (P< 0.05). Conclusions? The psychological capital of ICU nurses has negative correlation with their job burnout. Nursing managers should take certain measures based on each nurse's particular situation to improve their psychological capital so as to reduce the occurrence of job burnout.
7.Finite Element Analysis on Partially Closed and Fully Opened Aortic Valve
Guimei LIU ; Youlian PAN ; Wenyu FU ; Aike QIAO
Journal of Medical Biomechanics 2018;33(2):E095-E100
Objective To explore the effect of different initial state setting on a valve simulation. Methods Two-dimensional structural models were established with the initial state of the aortic valve being partially closed in one model and fully opened in the other. The time-dependent load was applied to the valve and the vessel wall of the aortic and the ventricle sides. The finite element method was used to study the maximum stress, the length of the joint, and the contact force of the closed aortic valve under two different initial states. Results The stress and contact force of the aortic valve were relatively large at the closed position when the initial state was fully opened. The closure degree of the valve was low, and the variations in stress and closure degree were large during the periodic cycle. The stress and contact force of the valve were relatively small when the aortic valve was partially closed. The closure degree was high, and the variations in stress and closure degree of the aortic valve were small during the periodic cycle. Conclusions In the case of the aortic valve partially closed in the initial state, the stability of the calculation process and the closure degree of the valve were relatively high, which should be given more consideration in numerical simulation. The results can be used to study the mechanical behavior of the valve and the biomechanical mechanism of the aortic root.
8.Effect of amygdala H2S system on depression-like behavior in posttraumatic stress disorder rats
Hongxia LIU ; Hong PAN ; Hua WANG ; Shunjun JIANG ; Zhang CAO ; Wenyu XIN
Chinese Journal of Pathophysiology 2017;33(6):988-992
AIM:To explore the depression-like behavior and cystathionine β-synthase (CBS)/hydrogen sulfide (H2S) levels of amygdala in posttraumatic stress disorder (PTSD) rats and to study the effect of exogenous H2S on PTSD rats.METHODS:Single prolonged stress paradigm was adopted to prepare PTSD animal model.Forced swimming test and sucrose preference test were used to evaluate the depression-like behavior.The content of CBS/H2S in amygdala tissue was measured by Western blot and methylene blue method.In vivo extracellular single unit recordings was used to examine the frequency of spontaneous discharges of amygdala neurons.RESULTS:The immobility time in forced swimming test of PTSD group increased and sucrose preference in sucrose preference test of PTSD group decreased compare with normal group (P<0.01).CBS/H2S level in amygdala tissue of PTSD group decreased compared with normal group (P<0.01).The immobility time of the rats in forced swimming test of NaHS+PTSD group decreased and the sucrose prefe-rence in sucrose preference test of NaHS+PTSD group increased compare with PTSD group (P<0.01).L-cysteine increased the frequency of spontaneous discharges of amygdala neurons (P<0.01).CONCLUSION:Depression-like behavior is aggravated in PTSD model rats owing to the inhibition of CBS/H2S content in amygdala tissue.The mechanism of behavior-improving effect of H2S on PTSD model rats is possibly related to excitating amygdala neurons and increasing the frequency of spontaneous discharges.
9. The clinical characteristics, gene mutations and prognosis of chronic neutrophilic leukemia
Yajuan CUI ; Qian JIANG ; Jinqin LIU ; Bing LI ; Zefeng XU ; Tiejun QIN ; Yue ZHANG ; Wenyu CAI ; Hongli ZHANG ; Liwei FANG ; Lijuan PAN ; Naibo HU ; Shiqiang QU ; Zhijian XIAO
Chinese Journal of Hematology 2017;38(1):28-32
Objective:
To investigate the clinical manifestation, cytogenetics, gene mutations and prognostic factors of chronic neutrophilic leukemia (CNL) .
Methods:
16 CNL cases, according to WHO (2016) -definition, were reviewed retrospectively. Identifications of the CSF3R, ASXL1, SETBP1, CALR and MPL mutations were performed by direct sequencing. JAK2 V617F mutation was detected by AS-PCR.
Results:
Of the 16 CNL patients, the median age was 64 (43-80) years with a male predominance of 75% (12/16) . The median hemoglobin was 114 (81-154) g/L, with median WBC of 41.20 (26.05-167.70) (109/L and median PLT of 238 (91-394) ×109/L.The median level of marrow fibrosis (MF) was 1 (0-3) degree. There was no other cytogenetic abnormalities except t (1;7) (p32;q11) , +21 and 14ps+ for each. All the 16 CNL patients harbored CSF3R T618I mutation. ASXL1 mutations were identified in 81% (13/16) , while SETBP1 mutations were confirmed in 63% (10/16) . The CALR K385fs*47 mutation was found. There was no mutation in JAK2 V617F or MPL in the above 16 patients. The median overall survival (OS) of patients presented with WBC≥50×109/L at diagnosis (11 months) was significantly shorter than of WBC<50×109/L (39 months,
10.Effect of psychological nursing on anxiety and depression and quality of life of patients with multi -drug ;resistant pulmonary tuberculosis
Yahong WU ; Xiaofang SHUI ; Wenyu CHEN ; Zhifen PAN ; Jinmei XU ; Hongyan ZHANG ; Jialiang LIU
Chinese Journal of Primary Medicine and Pharmacy 2016;23(19):2923-2926,2927
Objective To explore the effect of psychological nursing on anxiety and depression and quality of life of patients with multi drug resistant pulmonary tuberculosis.Methods 58 patients with multi -drug resistant pulmonary tuberculosis were randomly divided into observation group and control group,29 cases in each group.The control group received routine nursing care,the observation group received psychological nursing on the basis of the control group.Before and after psychological nursing intervention,the self rating anxiety scale(SAS)and depression self rating scale(SDS),health survey(SF -36)score were observed,and the clinical curative effect and compliance of the two groups were observed.Results After psychological nursing intervention,the SAS and SDS scores of the observation group[(36.83 ±7.61)points and (40.07 ±5.49)points]were significantly lower than the control group [(44.07 ±9.16)points and (43.90 ±7.91)points],the differences were statistically significant(t =3.27,2.14,all P <0.05).The SF -36 scores showed that after psychological nursing intervention,the physiological function(PF), physiological functions(RP),general health(GH),vitality(VT),social function(SF),role emotional(RE),mental health(MH),the seven dimensions scores of the observation group were significantly higher than those in the control group,the differences were statistically significant(t =7.18,10.22,8.85,12.71,12.04,9.68,4.79,all P <0.05). The compliance of the observation group was 93.10%,which of the control group was 72.41%,the difference was significant(χ2 =4.35,P <0.05).The total effective rate of the observation group was 86.21%,which of the control group was 62.07%,the difference was statistically significant(χ2 =4.41,P <0.05).Conclusion The psychological nursing intervention can improve the anxiety and depression of patients with multi -drug resistant tuberculosis, improve the quality of life of patients,improve the treatment compliance of patients,and improve the clinical efficacy.

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