1.Astragaloside Ⅳ improves pulmonary arterial hypertension by inhibiting p38 MAPK signaling pathway in SD rats
Yu LIU ; Bailin TANG ; Meili LU ; Hongxin WANG ; Yuhong YANG
Academic Journal of Naval Medical University 2025;46(8):1009-1017
Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT%)and percentage of the wall area to total vascular area(WA%)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P<0.01);the WA%and WT%of each dose group of AS-Ⅳ were decreased(all P<0.01),the expression of caspase 3 protein in lung tissue was decreased(all P<0.01),and the apoptosis of lung tissue cells was decreased(all P<0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P<0.01)and the expression of caspase 3 was decreased(all P<0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P<0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.
2.The clinical characteristics and microbial distribution of sepsis-induced myocardial injury
Sun YU ; Chunyang XU ; Hongwei YE ; Shun WEN ; Liang YANG ; Caiyun YANG ; Shiqi LU ; Meili SHEN
Chinese Journal of Emergency Medicine 2025;34(2):173-179
Objective:To investigate the clinical characteristics of sepsis-induced myocardial injury and microbial distribution.Methods:It was a retrospective observational study conducted from Jan 2023 to Dec 2023 in the Department of Emergency Intensive Care Medicine, Changshu Hospital Affiliated to Soochow University. Patients meeting the sepsis 3.0 criteria were included, excluding those with underlying cardiovascular diseases or incomplete data. Patients were categorized into myocardial injury (SIMI) and non-myocardial injury (Non-SIMI) groups based on troponin levels. General patient information, laboratory results, microbial findings, and prognostic indicators were collected. Differences in clinical parameters between the two groups were compared. Factors showing statistical differences in univariate analysis were further analyzed using multivariable logistic regression to identify risk factors for SIMI. Conduct propensity score matching among Pulmonary infection patients who underwent bronchoalveolar lavage high-throughput sequencing to compare microbial distribution between groups. Bracken was used to estimate species-level abundance from Kraken2 results, and α and β diversity analyses were conducted on the metagenomic samples.Results:A total of 179 patients were included in the study, with 98 (54.4%) in the Non-SIMI group and 81 (45.5%) in the SIMI group. There were 69 deaths overall (38.5%), with 23 (23.7%) in the Non-SIMI group and 46 (56.8%) in the SIMI group (χ 2=20.347, P<0.01). The 28-day survival curve indicated survival rates in the SIMI group were significantly lower compared to the Non-SIMI group (Log Rank χ 2=21.270, P<0.01). Univariate analysis revealed that fungal infection rate ( P=0.007), C-reactive protein ( P=0.021), procalcitonin, blood urea nitrogen, creatinine, alanine transaminase, and lactate levels were higher in the SIMI group compared to the Non-SIMI group (all P<0.01), prothrombin time was prolonger ( P<0.01) and APACHEⅡ scores were higher ( P<0.01), while serum albumin, base excess, and platelet levels were lower (all P<0.01). Multivariable logistic regression analysis indicated that fungal infection ( OR=3.441, P=0.015) was a risk factor for SIMI, whereas base excess and platelets were protective factors ( OR=0.845, 0.988, both P<0.01). Comparison of bronchoalveolar lavage high-throughput sequencing results in the pulmonary infection subgroup showed the relative abundance of Haemophilus paraininfluenzae in Non-SIMI group was higher than SIMI group among the top 20 species ( P=0.013). There were no statistically significant differences in microbial αand β-diversity between the two groups. Conclusions:The incidence of SIMI is relatively highamong sepsis patients and it affects their prognosis. Risk factors for SIMI include fungal infection, decreased platelet count, and reduced base excess levels. Among patients with pulmonary infections, there is a lower risk of SIMI associated with Haemophilus influenzae infection.
3.Perioperative risk factors for chronic kidney disease after acute type A aortic dissection repair: A retrospective cohort study
Pianpian YAN ; Xijie WU ; Shengwen GUO ; Yiting HUANG ; Meili LU ; Lulu JIANG ; Yanqing ZHOU ; Jiarong MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1588-1596
Objective To investigate the renal function recovery and perioperative risk factors for chronic kidney disease in patients after acute Stanford type A aortic dissection (ATAAD) repair. Methods A retrospective study was conducted on patients who underwent ATAAD repair at the Xiamen Cardiovascular Hospital, Xiamen University from 2020 to 2021, and their clinical data were analyzed. Results A total of 255 patients were included, with 200 males and 55 females, and an average age of (52.80±12.46) years. The incidence of acute kidney injury (AKI) after ATAAD repair was 43.9%. Dissection involving the renal artery [OR=2.144, 95%CI (1.234, 3.765), P=0.007], intraoperative urine output [OR=0.761, 95%CI (0.625, 0.911), P=0.004], and intraoperative red blood cell transfusion [OR=1.288, 95%CI (1.088, 1.543), P=0.004] were significantly associated with early AKI after ATAAD repair. Long-term renal function follow-up data were available for 232 patients, among whom 40 (17.2%) patients developed chronic kidney disease (CKD). Independent predictors for CKD included lower body mass index [OR=0.827, 95%CI (0.723, 0.931), P=0.003], preoperative cardiac tamponade [OR=5.344, 95%CI (1.65, 17.958), P=0.005], preoperative renal hypoperfusion syndrome [OR=12.629, 95%CI (5.003, 35.373), P<0.001], postoperative peak serum creatinine time>3 d [OR=7.566, 95%CI (2.799, 22.731), P<0.001], and AKI grade [grade 1: OR=4.418, 95%CI (1.339, 15.361), P=0.016; grade 2: OR=8.345, 95%CI (1.762, 40.499), P=0.007; grade 3: OR=9.463, 95%CI (2.602, 37.693), P<0.001]. Conclusion AKI related to ATAAD repair can recover in the early postoperative period, but both the duration and severity of AKI will affect long-term renal function. In addition, patients' nutritional status, preoperative cardiac tamponade, and renal hypoperfusion syndrome are also independent risk factors for long-term renal dysfunction.
4.Efficacy of lenalidomide in treatment of multiple myeloma and its effect on levels of regulatory T cells and natural killer cells of patients
Jianjun BIAN ; Lei SHEN ; Liang LI ; Yuxuan SU ; Jinman ZUO ; Meili MENG ; Yao LU ; Shuya GE ; Lei FU
Journal of Leukemia & Lymphoma 2023;32(7):400-404
Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.
5.Study of the value of SPECT lung perfusion imaging in optimizing lung cancer radiotherapy plan for lung function protection
Ji LIU ; Meili HAO ; Ye TAN ; Xiaohong JIANG ; Haijun LU
Chinese Journal of Radiation Oncology 2021;30(11):1117-1121
Objective:To evaluate the application value of SPECT lung perfusion imaging in guiding radiotherapy path, optimizing the radiotherapy plan for lung cancer and protecting lung function during radiotherapy for locally advanced non-small cell lung cancer.Methods:In this study, 84 patients with stage Ⅲ non-resectable non-small cell lung cancer were randomly divided into the control group ( n=44) and observation group ( n=40). In the control group, radiotherapy plan based on conventional CT images was delivered, and two plans based on the lung function information suggested by conventional CT and SPECT lung perfusion imaging: P1 and P2 were given in the observation group. All patients in the observation group were finally treated according to the P2 plan. The incidence of radiation pneumonitis, and changes in lung function before and after radiotherapy were statistically compared between two groups. The dose-volume parameters of P1 and P2 were statistically compared. Results:After the plan was optimized, the incidence of radiation pneumonitis in the observation group was significantly reduced and the decline of lung function was significantly improved (both P≤0.001). The functional dose parameters were significantly improved in the P2 plans (both P<0.05), whereas the irradiation dose of organs at risk did not significantly change ( P>0.05). Conclusion:SPECT lung perfusion imaging optimizes the intensity-modulated radiotherapy plan, which can reduce the functional lung dose and increase the tumor radiotherapy dose without increasing the irradiation dose of other organs at risk.
6.Neuromyelitis optica spectrum disorders complicated with immune thrombocytopenia: a case report
Lei FU ; Lei SHEN ; Jianjun BIAN ; Liang LI ; Jinman ZUO ; Shuya GE ; Yao LU ; Meili MENG ; Yuxuan SU
Chinese Journal of Neurology 2021;54(9):943-945
Neuromyelitis optica spectrum disorders (NMOSD) are a severe autoimmune inflammatory demyelinating disease of the central nervous system. NMOSD complicated with immune thrombocytopenia (ITP) is rare. This paper reports a case of NMOSD who was misdiagnosed as multiple sclerosis for many years, and then developed thrombocytopenia. ITP was diagnosed by perfect examination. After immunosuppression and thrombopoiesis therapy, the platelets returned to normal. The review of the case and literatures can help to improve the understanding of this kind of disease, timely diagnose and treat patients, and avoid serious complications.
7.Analysis of SATB2 gene mutation in a child with Glass syndrome.
Meili LIN ; Ruen YAO ; Jing LU ; Wei CHEN ; Yufei XU ; Guoqiang LI ; Tingting YU ; Yanrong QING ; Xingming JIN ; Jian WANG
Chinese Journal of Medical Genetics 2019;36(7):712-715
OBJECTIVE:
To analyze the clinical characteristics and genetic basis of a child affected with Glass syndrome.
METHODS:
Clinical manifestations and auxiliary examination results of the child were analyzed. Potential mutation was detected with next generation sequencing and validated by Sanger sequencing.
RESULTS:
The child has featured growth and mental retardation, delayed speech, cleft palate, crowding of teeth, and downslanting palpebral fissures. DNA sequencing revealed a de novo heterozygous missense mutation c.1166G>A (p.R389H) in exon 8 of the SATB2 gene in the child.
CONCLUSION
The heterozygous mutation c.1166G>A (p.R389H) of the SATB2 gene probably account for the Glass syndrome in the patient.
Abnormalities, Multiple
;
genetics
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Child
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Chromosome Deletion
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Chromosomes, Human, Pair 2
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Humans
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Intellectual Disability
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genetics
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Matrix Attachment Region Binding Proteins
;
genetics
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Mutation
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Transcription Factors
;
genetics
8.Application of functional imaging technology in radiotherapy for lung cancer
Meili HAO ; Li SUN ; Xiao DING ; Haijun LU
Journal of International Oncology 2019;46(6):370-373
Functional imaging plays an important role in lung cancer radiotherapy.Functional imaging techniques include single photon emission computed tomography,positron emission tomography,magnetic resonance imaging,and computed tomography.Using lung function information provided by these techniques for lung cancer radiotherapy can better protect the normal function of lung tissue,optimize the radiotherapy program,and reduce the incidence of radiation pneumonitis.With the development of perfusion and imaging technology,functional imaging technology is expected to be widely used in the precise radiotherapy of lung cancer in the future.
9.Effect of real-time visual feedback on manual chest compression in ambulance
Jiangang WANG ; Meili LU ; Lina QIAN ; Guohao YANG ; Jingcai XU
Chinese Journal of Emergency Medicine 2018;27(1):57-60
Objective To investigate the efficacy of real-time visual feedback on improving the quality of manual chest compression in ambulance.Methods Ten pre-hospital doctors with cardiopulmonary resuscitation experience,aged under 40 years,were recruited to this randomized,crossover,manikin research and randomly assigned into control group (n=5) and feedback group (n=5) by the sealed envelope method.The setting place was a moving ambulance with the velocity of 25~50 km/ h.The whole process consisted of two sessions.In control group,which received feedback in the second session,chest compressions were performed without interruption during each of the three 2 min phases per session,resting for 2 min between phases and for 5 min between sessions.In feedback group,which received feedback in the first session,chest compressions were performed without interruption during each of the three 2 min phases per session,resting for 2 min between phases and for 5 min between sessions.Data of compression rate,compression depth,compression detention and compression accuracy rate were collected.Results In control group,the compressions rate was lower and compression detention was shorter during the second session compared with those during the first session [(109.8±±4.7) r/min vs.(121.2± 10.1) r/min,(6.5±2.1) r/min vs.(10.4±2.8) r/min,all P<0.05],while the compression accuracy rate during the second session was higher than that during the first session [(28.2±±14.3) % vs.(16.8±9.9) %,P<0.05].There was no significant difference in compression rate between the two sessions in control group;Compression frequency,compression depth,compression detention and compression accuracy rate did not significantly change between the two sessions in feedback group (all P>0.05).In the whole process,the compression rate was lower and compression detention was shorter in the feedback group compared with the control group [(111.1±5.1) r/min vs.(115.5±9.7) r/min,(6.5±1.8) vs.(8.4±4.6) r/min,all P<0.05],and the compression accuracy rate in the feedback group was higher than that in the control group[(22.5±13.4) % vs.(26.7±16) %,P<0.05].There was no significant difference in compression rate between the two groups during whole process (P>0.05).Conclusions Although real-time visual feed back improved the quality of manual chest compression in ambulances,which demonstrated more reasonable compression rate,less compression detention and higher compression accuracy,the overall quality of reuscitation was still not enough to achieve effective treatment.This implies that more optimal methods are required to transfer the patients suffering cardiac arrest.
10.The influence of LPS on the protein expression of related molecules in Smads and ERK1/2 signal pathway in LTC-14 cells
Qing ZHANG ; Kai CHEN ; Meili LU ; Wei XU ; Xiaohui XIANG ; Shihai XIA ; Runli JI
Chinese Journal of Pancreatology 2017;17(2):93-98
Objective To explore the influence of LPS treatment on related molecules in Smads and ERK1/2 signal pathway in pancreatic stellate cell line LTC-14.Methods LTC-14 cells were cultured in vitro, and were treated with LPS at different dose in different time points.Protein expressions of related molecules in Smads pathway and ERK1/2 pathway and α-SMA in LTC-14 Cells were examined by Western blot.Results On Treated LTC-14 cells by 0, 1, 5, 10, 20 and 50 mg/L LPS,protein expressions of Smad3 were 0.15±0.02, 0.37±0.02, 0.44±0.01, 0.46±0.02, 0.372±0.01 and 0.24±0.03;expressions of Smad7 were 0.79±0.05, 0.84±0.02, 0.55±0.03, 0.45±0.03, 0.34±0.02 and 0.92±0.07;p-ERK1/2 levels were 0.48±0.05, 0.74±0.03, 0.72±0.04, 0.89±0.02, 0.81±0.02 and 0.72±0.03;p-cPLA2 levels were 0.15±0.03, 0.30±0.01, 0.31±0.01, 0.30±0.02, 0.28±0.03 and 0.32±0.02;α-SMA levels were 0.56±0.06, 0.62±0.06, 0.54±0.04, 1.03±0.11, 1.39±0.08 and 1.28±0.10.The changes of protein expressions before and after LPS treatment were obvious (all P<0.01).The protein expressions of ERK1/2 were 0.56±0.03, 0.57±0.02, 0.53±0.02, 0.58±0.02, 0.59±0.05 and 0.55±0.04, which did not change obviously along with increased LPS dosages.LTC-14 cells treated with 10 mg/L LPS for 0, 1, 3, 6 and 9 h,the expressions of Smad3 were 0.69±0.05, 0.68±0.07, 1.02±0.14, 1.82±0.0 and 2.04±0.11,those of Smad7 were 2.77±0.10, 1.37±0.08, 1.45±0.14, 0.78±0.09 and 0.63±0.06,those of p-ERK1/2 were 0.16±0.03, 0.32±0.05, 0.79±0.03, 1.50±0.07 and 1.77±0.04,those of p-cPLA2 were 0.15±0.04, 0.32±0.06, 0.63±0.04, 0.95±0.04 and 1.49±0.10,those of α-SMA were 0.84±0.03, 1.26±0.21, 1.81±0.19, 4.28±0.26 and 4.37±0.15, all of which changed obviously as the treatment time increased (P<0.05 or 0.01).The expressions of ERK1/2 were 0.75±0.03, 0.72±0.02, 0.80±0.04, 0.74±0.03 and 0.85±0.09, which did not change obviously as the treatment time increased.Conclusions LPS could upregulate the expression of α-SMA in a time-and dose-dependent way, and activate intracellular Smads and ERK1/2 inflammatory pathways, which may be the potential molecular mechanism of the development of chronic pancreatitis.

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