1.Eplerenone alleviates rheumatoid arthritis in mice by inhibiting macrophage M1 polarization through Kv1.3/Bcl-2/NF-κB pathway
Chi XIAO ; Jing CAI ; Zi-hang WANG ; Yong-zheng ZHANG ; Jing YANG ; Lu-feng CHENG
Chinese Pharmacological Bulletin 2025;41(4):726-737
Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P<0.05,P<0.01),and the high-dose EPL group reduced the serum RF in mice(P<0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P>0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P<0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P<0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P<0.01).EPL significantly increased the pro-tein expression of Bcl-2(P<0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P<0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.
2.Eplerenone alleviates rheumatoid arthritis in mice by inhibiting macrophage M1 polarization through Kv1.3/Bcl-2/NF-κB pathway
Chi XIAO ; Jing CAI ; Zi-hang WANG ; Yong-zheng ZHANG ; Jing YANG ; Lu-feng CHENG
Chinese Pharmacological Bulletin 2025;41(4):726-737
Aim To investigate the effect of eplerenone(EPL)on the alleviation of rheumatoid arthritis(RA)based on voltage-gated potassium channel 1.3(Kv1.3)/B-cell lymphoma-2(Bcl-2)/nuclear factor-κB(NF-κB)to inhibit macrophage M1 polarization in mice.Methods Bioinformatics technology was used to screen disease pathways and targets,and the binding affinity and stability of EPL-Kv1.3 complex system were calculated.A mouse model of RA was established and treated with EPL by intragastric administration for 42 days.The indicators reflecting drug remission of RA were recorded and detected.RAW264.7 cells were treated with EPL to detect the indicators reflecting the effect of drugs on macrophage M1 polarization,and to verify the upstream and downstream key targets of re-lated signaling pathways mediated by drugs.Results Bioinformatics analysis showed that the disease targets were mainly involved in inflammatory response and NF-κB signaling pathway,and EPL-Kv1.3 had high affinity and stable binding.In animal experiments,the detec-tion of anti-cyclic citrullinated peptide antibody(CCP-Ab)and joint score indicated the successful establish-ment of the model.Compared with the model group,EPL could reduce the toe redness and swelling score,alleviate the plantar redness and swelling,synovial swelling,and reduce fibrosis and inflammatory cell in-filtration in mice.The medium-dose and high-dose EPL groups reduced the HE staining score(P<0.05,P<0.01),and the high-dose EPL group reduced the serum RF in mice(P<0.01).CCK-8 results showed that low,medium and high doses of EPL had no effect on the activity of RAW264.7 macrophages(P>0.05).Compared with the model group,EPL treatment significantly reduced the contents of IL-6,TNF-α and NO in supernatant of the cells(P<0.01),reduced the nuclear translocation of NF-KB-p65 in the high-dose EPL group,reduced the M1 polarization and increased the proportion of M2 polarization in the medium and high-dose EPL groups(P<0.01).The mRNA levels of MyD88,IκB-α,NF-κB-p65,NF-KB-p50,IL-1 β and iNOS were significantly reduced in each dose group of EPL(P<0.01).EPL significantly increased the pro-tein expression of Bcl-2(P<0.01)and decreased the protein expression of Kv1.3,MyD88,p-IκB-α/IκB-α,p-p65/p65,IL-1 β and iNOS(P<0.05).Conclusion EPL may play an immunomodulatory role in relieving RA in mice by regulating Kv1.3/Bcl-2/NF-κB path-way,reducing macrophage M1 polarization and amelio-rating macrophage-associated inflammatory response.
3.Effects of different dose prediction models of sufentanil during hip arthroplasty with bow tie fascia iliac block
Hong CHEN ; Ming-Feng LIAO ; Shi-Yong LI ; Ai-Lin LUO ; Xiao-Hui CHI
Journal of Regional Anatomy and Operative Surgery 2024;33(11):949-954
Objective To compare the effects of different dose prediction models of sufentanil in elderly hip arthroplasty with ultrasound-guided bow tie fascia iliac block.Methods A total of 90 elderly patients who underwent ultrasound-guided bow tie fascia iliac during hip arthroplasty in our hospital from June 2018 to June 2022 were selected.The dose of sufentanil was determined by a linear regression(ALR),multiple linear regression(MLR)or deep belief networks(DBN).Patients were randomly divided into the ALR group,the MLR group and the DBN group,with 30 cases in each group.The analgesic effect,hemodynamic index,inflammatory factor level and surgical index were compared among all groups.Kaplan-Meier method was used to analyze the incidence of hip infection 2 weeks after surgery in each group.Results There was no significant difference in the gender,age,body weight,American Society of Anesthesiologists(ASA)classification or complications among all groups(P>0.05).The Harris score 24 hours after surgery and duration of sensory block in the DBN group were higher/longer than those in the ALR group,numerical rating scale(NRS)score 24 hours after surgery,mean arterial pressure(MAP)and heart rate(HR)at the beginning of surgery and 30 minutes after surgery,levels of interleukin-17(IL-17)and tumor necrosis factor-α(TNF-α)24 hours after surgery,onset time of sensory block,and number of patient controlled analgesia(PCA)compression were lower/earlier/less than those in the ALR group,the modified observer's assessment of alertness/sedation scale(OAA/S)score 24 hours after surgery was significantly lower than those in the ALR group and the MLR group,with statistically significant differences(P<0.05).Harris score 24 hours after surgery and duration of sensory block in the MLR group were higher/longer than those in the ALR group,modified OAA/S score 12 hours after surgery,MAP 30 minutes after surgery,levels of IL-17 and TNF-α 24 hours after surgery,onset time of sensory block,and the number of PCA compressions were lower/longer/less than those in the ALR group,with statistically significant differences(P<0.05).Kaplan-Meier analysis showed that there were significant differences in the incidences of hip infection 2 weeks after surgery among all groups(P<0.05),and there were significant differences in the incidences of hip infection 2 weeks after surgery between the ALR group and the DBN group(P<0.05).Conclusion The effectiveness of calculating the dose of sufentanil using the MLR and DBN in elderly hip arthroplasty with bow tie fascia iliac block is better than that of ALR,and the advantage of DBN is more obvious.
4.Concept analysis and enlightenment of mobile health readiness
Yongzhen GUO ; Ruotong PENG ; Xiao-yang LI ; Chi ZHANG ; Hui FENG
Chinese Journal of Nursing 2024;59(23):2940-2944,后插1
Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.
5.Clinical management of refractory prolactinomas:stone to sharpen yan,blunt for profit
Rui-Feng WANG ; Xiao-Zhen YE ; Jian-Rui LI ; Jing LI ; Jia-Liang LI ; Zi-Xiang CONG ; Yan LU ; Nan WU ; Yi-Feng GE ; Chi-Yuan MA ; Jia-Qing SHAO
Medical Journal of Chinese People's Liberation Army 2024;49(11):1237-1243
Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.
6.Concept analysis and enlightenment of mobile health readiness
Yongzhen GUO ; Ruotong PENG ; Xiao-yang LI ; Chi ZHANG ; Hui FENG
Chinese Journal of Nursing 2024;59(23):2940-2944,后插1
Objective To analyze the definition of mobile health readiness,and provide a theoretical basis for assessment and clinical practice.Methods Web of Science,PubMed,Embase,Cochrane Library,CINAHL,CNKI,Wanfang data,VIP,and China Biomedical Literature Service System databases were searched.The search time limit was from the establishment of the database to January 2024.Walker and Avant's methods were used to perform concept analysis.Results As a result,38 articles were selected for analysis.Mobile health readiness can be classified into 4 defined attributes:willingness to adopt new technologies,digital health literacy,technological accessibility,and supporting environment and resources.Antecedents can be discussed from the aspects of digital gap,health care service,and user factors.Mobile health readiness can impact on users and health care systems.Conclusion The concept attributes of mobile health readiness were identified by concept analysis method,which provides references for community nurses to assess the mobile health readiness of users.In the future,researchers can combine the connotations of mobile health readiness to develop assessment tools,and construct interventions for the implementation of mobile health,thereby promoting the application of mobile health in China and the development of intelligent nursing.
7.Clinical outcomes of minimally invasive coronary artery bypass grafting in 239 patients: A propensity score matching study
Feng PAN ; Lin LIANG ; Wei XIAO ; Jiaji LIU ; Xiaolong MA ; Danqing GENG ; Guangxin ZHAO ; Liqun CHI ; Qingyu KONG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):976-981
Objective To investigate the perioperative clinical effects and follow-up results of minimally invasive coronary artery bypass grafting (MICS CABG) versus conventional coronary artery bypass grafting (CABG) in thoracotomy. Methods The patients who received off-pump CABG in Beijing Anzhen Hospital from January 2017 to October 2021 were collected. Among them, the patients receiving MICS CABG performed by the same surgeon were divided into a minimally invasive group, and the patients receiving median thoracotomy were into a conventional group. By propensity score matching, preoperative data were balanced. Perioperative and postoperative follow-up data of the two groups were compared. Results A total of 890 patients were collected. There were 211 males and 28 females, aged 60.54±9.40 years in the minimally invasive group, and 487 males and 164 females, aged 62.31±8.64 years in the conventional group. After propensity score matching, there were 239 patients in each group. Compared with the conventional group, patients in the minimally invasive group had longer operation time, shorter drainage duration, less drainage volume on the first postoperative day, shorter postoperative hospital stay, and lower rate of positive inotropenic drugs use, while there was no statistical difference in the mean number of bypass grafts, ICU stay, ventilator-assisted time, blood transfusion rate or perioperative complications (P>0.05). During the median follow-up of 2.25 years, there was no statistical difference in major adverse cardiovascular and cerebrovascular events, including all-cause death, stroke or revascularization between the two groups (P>0.05). Conclusion Reasonable clinical strategies can ensure perioperative and mid-term surgical outcomes of MICS CABG not inferior to conventional CABG. In addition, MICS CABG has the advantages in terms of postoperative hospital stay, postoperative drainage volume, and rate of positive inotropic drugs use.
8.Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS.
Jin-Chao XIAO ; Ling WANG ; Li ZHANG ; Ming-Yan CHI ; Yong HUANG ; Zi-Peng GONG ; Lin ZHENG ; Feng HE
China Journal of Chinese Materia Medica 2023;48(22):6183-6190
Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.
Rats
;
Humans
;
Animals
;
Tandem Mass Spectrometry/methods*
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Chromatography, Liquid/methods*
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Rats, Sprague-Dawley
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Liquid Chromatography-Mass Spectrometry
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Protein Binding
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Renal Dialysis
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Drugs, Chinese Herbal
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Blood Proteins
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Chromatography, High Pressure Liquid/methods*
9.Congenital factor X deficiency: a retrospective analysis of 11 cases.
Rong Wei LI ; Xiao Fan LIU ; Feng XUE ; Yun Fei CHEN ; Wei LIU ; Rong Feng FU ; Lei ZHANG ; Rong Chi YANG
Chinese Journal of Hematology 2022;43(1):26-30
Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.
Adolescent
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Adult
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Blood Coagulation Factors/therapeutic use*
;
Blood Coagulation Tests
;
Child
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Child, Preschool
;
Factor X Deficiency/genetics*
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Female
;
Hemorrhage/drug therapy*
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Humans
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Male
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Middle Aged
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Plasma
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Retrospective Studies
;
Young Adult
10.Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China.
Bi-Jun SHI ; Ying LI ; Fan WU ; Zhou-Shan FENG ; Qi-Liang CUI ; Chuan-Zhong YANG ; Xiao-Tong YE ; Yi-Heng DAI ; Wei-Yi LIANG ; Xiu-Zhen YE ; Jing MO ; Lu DING ; Ben-Qing WU ; Hong-Xiang CHEN ; Chi-Wang LI ; Zhe ZHANG ; Xiao RONG ; Wei SHEN ; Wei-Min HUANG ; Bing-Yan YANG ; Jun-Feng LYU ; Hui-Wen HUANG ; Le-Ying HUO ; Hong-Ping RAO ; Wen-Kang YAN ; Xue-Jun REN ; Yong YANG ; Fang-Fang WANG ; Dong LIU ; Shi-Guang DIAO ; Xiao-Yan LIU ; Qiong MENG ; Yu WANG ; Bin WANG ; Li-Juan ZHANG ; Yu-Ge HUANG ; Dang AO ; Wei-Zhong LI ; Jie-Ling CHEN ; Yan-Ling CHEN ; Wei LI ; Zhi-Feng CHEN ; Yue-Qin DING ; Xiao-Yu LI ; Yue-Fang HUANG ; Ni-Yang LIN ; Yang-Fan CAI ; Sha-Sha HAN ; Ya JIN ; Guo-Sheng LIU ; Zhong-He WAN ; Yi BAN ; Bo BAI ; Guang-Hong LI ; Yue-Xiu YAN
Chinese Journal of Contemporary Pediatrics 2022;24(1):33-40
OBJECTIVES:
To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.
METHODS:
A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.
RESULTS:
Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).
CONCLUSIONS
There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology*
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Female
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Gestational Age
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Humans
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Infant
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Infant, Extremely Premature
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Infant, Newborn
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Pregnancy
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Respiratory Distress Syndrome, Newborn/epidemiology*
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Retrospective Studies
;
Treatment Outcome

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