1.Bone marrow mesenchymal stem cell transplantation improves airway inflammation due to chronic asthma
Qi ZHANG ; Ruirui GUO ; Jiangping HU
Chinese Journal of Tissue Engineering Research 2016;20(10):1494-1500
BACKGROUND:Studies have shown that bone marrow mesenchymal stem cel transplantation can improve disease conditions by reducing inflammation.
OBJECTIVE:To explore the therapeutic efficacy of bone marrow mesenchymal stem cels on chronic asthma rats.
METHODS: A rat model of chronic asthma was established by intraperitonealy injected and aerosolized ovalbumin. After modeling, rats were given 4×105 and 8×105 bone marrow mesenchymal stem celsvia the tail vein, respectively. Thirty days later, the lung tissues were observed pathologicaly using hematoxylin-eosin staining; RT-qPCR and ELISA methods were employed to test the changes in interleukin-10, tumor necrosis factor-α and interferon-γ levels in lung tissue and peripheral blood, respectively.
RESULTS AND CONCLUSION:Rat models of chronic asthma were successfuly established after intraperitoneal injection of ovalbumin combined with aerosolized ovalbumin. After 30 days of cel treatment, the structure of lung tissues were obviously recovered, and the levels of interleukin-10, tumor necrosis factor-α and interferon-γ showed some improvement in lung tissue and peripheral blood, but there were no differences between the two groups. In conclusion, bone marrow mesenchymal stem cels show some potential role in the treatment of chronic asthma.
2.Value of bedside index for severity in acute pancreatitis scoring system in diagnosing severe acute pancreatitis
Ruirui HU ; Qi ZHANG ; Zibin TIAN ; Xinjuan KONG ; Huiguang XUE ; Liangzhou WEI ; Qingxi ZHAO
Chinese Journal of Pancreatology 2011;11(4):231-233
Objective To evaluate the value of the Bedside Index for Severity in Acute Pancreatitis (BISAP) in diagnosing severe acute pancreatitis. Methods Sixty-eight patients with suspected diagnosis of severe acute pancreatitis were collected and were scored by BISAP, APACHE Ⅱ , Ranson and CTSI scoring systems, respectively. BISAP scoring system included the blood urea nitrogen, impaired mental status,systemic inflammatory response syndrome, age, and pleural effusion. The diagnosis criteria of severe acute pancreatitis was BISAP ≥ 3 points or APACHE IⅡ ≥ 8 points, Ranson ≥ 3 points, CTSI ≥ 3 points. The diagnostic accuracy of SAP of these scoring systems was calculated. Results Among these 68 cases, 63.2%(43/68) were graded ≥ 3 points in BISAP scoring system;60.3% (41/68) were marked ≥8 points in APACHE Ⅱ scoring system; 60.3% (41/68) were scored ≥ 3 points in Ranson scoring system; and 67.6%(46/68) were scored ≥3 points in CTSI scoring system. There was no statistical difference between BISAP scoring system and other three scoring systems in diagnosing severe acute pancreatitis. Conclusions As a new and simple scoring system, BISAP scoring system can be widely used in the diagnosis of severe acute pancreatitis.
3.The expression changes and clinical significance of serum microRNA-155 and 135b-5p in patients with peptic ulcer complicated with Helicobacter pylori infection
Kuankuan AI ; Ruirui HU ; Yuan XUE ; Yan WANG
Chinese Journal of Postgraduates of Medicine 2024;47(3):237-241
Objective:To investigate the expression levels and clinical significance of serum microRNA (miR) -155 and miR-135b-5p in patients with peptic ulcer complicated with Helicobacter pylori ( Hp) infection. Methods:A prospective study was conducted, and 263 patients with peptic ulcer were selected consecutively from July 2021 to February 2023 at the Affiliated Hospital of Jining Medical College. Among them, 146 cases were confirmed as Hp infection ( Hp infection group) and 117 cases were not complicated with Hp infection (non Hp infection group) by 14C breath test; type Ⅰ Hp infection was in 110 cases, and type Ⅱ Hp infection was in 36 cases by immunoblotting method. The serum expression levels of miR-155 and miR-135b-5p were detected by real-time fluorescence quantitative polymerase chain reaction, serum gastrin level was detected by radioimmunoassay method, and the serum pepsinogen (PG) Ⅰ and PG Ⅱ were detected by enzyme linked immunosorbent assay. The clinical data were recorded. Multivariate Logistic regression analysis was used to analyze the independent risk factors of Hp infection in patients with peptic ulcer; receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum miR-155 and miR-135b-5p in diagnosis the Hp infection in patients with peptic ulcer. Results:The gastrin, PG Ⅰ, PG Ⅱ, ulcer bleeding rate and recurrence rate in Hp infection group were significantly higher than those in non Hp infection group: (108.47 ± 15.35) ng/L vs. (79.63 ± 10.58) ng/L, (295.41 ± 37.26) pg/L vs. (236.75 ± 29.17) pg/L, (44.08 ± 8.52) pg/L vs. (39.29 ± 6.74) pg/L, 25.34% (37/146) vs. 15.38% (18/117) and 21.92% (32/146) vs. 11.97% (14/117), and there were statistical differences ( P<0.01 or <0.05). The serum miR-155 and miR-135b-5p in Hp infection group were significantly higher than those in non Hp infection group (1.94 ± 0.63 vs. 0.95 ± 0.29 and 1.86 ± 0.57 vs. 1.03 ± 0.31), and there were statistical differences ( P<0.01). The serum miR-155 and miR-135b-5p in patients with typeⅠ Hp infection were significantly higher than those in patients with type Ⅱ Hp infection (2.05 ± 0.66 vs. 1.60 ± 0.54 and 1.97 ± 0.61 vs. 1.52 ± 0.45), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that serum miR-155, miR-135b-5p, gastrin and PG Ⅰwere independent risk factors of Hp infection in patients with peptic ulcer ( OR = 1.443, 1.436, 1.452 and 1.438; 95% CI 1.165 to 1.787, 1.146 to 1.799, 1.187 to 1.777 and 1.150 to 1.798; P<0.01). ROC curve analysis result showed that the area under the curve of serum miR-155 combined with miR-135b-5p in the diagnosis of Hp infection in patients with peptic ulcer was significantly greater than that of serum miR-155 and miR-135b-5p alone (0.907 vs. 0.839 and 0.836, Z = 2.57 and 2.81, P = 0.010 and 0.005). Conclusions:The serum levels of miR-155 and miR-135b-5p are high in patients with peptic ulcer complicated with Hp infection, and the combination of the two has high diagnostic value for Hp infection in patients with peptic ulcer.
4.Nucleomodulin BspJ as an effector promotes the colonization of Brucella abortus in the host
Zhongchen MA ; Shuifa YU ; Kejian CHENG ; Yuhe MIAO ; Yimei XU ; Ruirui HU ; Wei ZHENG ; Jihai YI ; Huan ZHANG ; Ruirui LI ; Zhiqiang LI ; Yong WANG ; Chuangfu CHEN
Journal of Veterinary Science 2022;23(1):e8-
Background:
Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified.
Objectives:
To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles.
Methods:
Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro.
Results:
BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella.
Conclusions
BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.
6.Secondary donor-derived CD19 CAR-T therapy is safe and efficacious in acute lymphoblastic leukemia with extramedullary relapse after first autologous CAR-T therapy.
Delin KONG ; Tingting YANG ; Jia GENG ; Ruirui JING ; Qiqi ZHANG ; Guoqing WEI ; He HUANG ; Yongxian HU
Journal of Zhejiang University. Science. B 2022;23(10):876-880
Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult
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Antigens, CD19
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Hematopoietic Stem Cell Transplantation
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Humans
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Immunotherapy, Adoptive/adverse effects*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
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Receptors, Chimeric Antigen
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Recurrence
7.Meta-analysis of Effect of Tripterygium wilfordii Polyglycoside Tablets Combined with Methotrexate and/or Leflunomide on Autoantibodies in Rheumatoid Arthritis
Chao YANG ; Zhixing HU ; Ruirui MING ; Tengteng XU ; Luochangting FANG ; Xiaoxiao WANG ; Taixian LI ; Lin CHEN ; Chunfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):39-48
ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets (TWPT) combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) and/or leflunomide (LEF) on autoantibodies in rheumatoid arthritis (RA) patients. MethodPubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, and China Biomedical Literature Service System (SinoMed) were searched for randomized controlled trials (RCTs) of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1, 2021. Primary outcome indicators included rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA), and secondary outcome indicators included immunoglobulin (IgA, IgG, and IgM) and adverse drug events (ADE). ResultThirty-one RCTs, involving 2 643 adult patients, were included, including 20 RCTs of TWPT combined with MTX, 10 of TWPT combined with LEF, and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone, TWPT combined with other drugs significantly improved serum RF of RA patients [SMD=-2.45, 95% CI [-2.97, -1.93], P<0.000 01], anti-CCP [SMD=-1.41, 95% CI (-2.35, -0.48), P=0.003], IgM [SMD=-1.90, 95% CI (-3.03, -0.76), P=0.001], and IgA [SMD=-1.18, 95% CI (-2.23, -0.12), P=0.03]. There were no significant effects on IgG [SMD=-1.02, 95% CI (-2.04, 0.01), P=0.05] and ADE [RR=0.87, 95% CI (0.66, 1.15), P=0.32]. ConclusionThe results of this study show that compared with csDMARDs alone, TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However, due to the limited quality and quantity of the included RCTs, the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA, and more high-quality studies are still needed to further confirm their efficacy.
8.Anti-swelling and Analgesic Mechanism of Jianpi Tongluo Prescription from MAPKs Signaling Pathway
Ruirui MING ; Changting FANG-LUO ; Xiaoxiao WANG ; Zhixing HU ; Chao YANG ; Tengteng XU ; Hongjie WANG ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):85-93
ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription (JPTL) and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group, model group, JPTL low-, medium- and high-dose groups (5, 10, 20 g·kg-1) and positive drug (celecoxib, 0.03 g·kg-1) group, with 10 in each group (po,once a day). Complete freund's adjuvant (CFA) was used to induce the model of chronic inflammatory pain, and xylene-induced ear swelling test, hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and inflammatory paw of mice with chronic inflammatory pain, and the expressions of aquaporin 1 (AQP1), aquaporin 3 (AQP3), cyclooxygenase 1 (COX1), cyclooxygenase 2 (COX2) and mitogen-activated protein kinases (MAPKs) in inflammatory paw were detected by Western blot, to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group, there was a significant increase in the ear swelling of xylene-induced model mice, a shortened paw withdrawal latency in the hot plate test (P<0.01). Compared with the model group, JPTL remarkably increased the inhibition rate of xylene-induced ear swelling (P<0.05, P<0.01), prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing (P<0.05, P<0.01). Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased, the threshold of mechanical pain was decreased and the threshold of cold pain was increased (P<0.05, P<0.01), the protein contents of AQP1 and AQP3 in inflammatory feet were increased, and the contents of IL-1β, IL-6, TNF-α, PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK, p-JNK and p-ERK in inflammatory feet were increased (P<0.01). Compared with the model group, JPTL relieved paw swelling of mice with chronic inflammatory pain, elevated mechanical withdrawal threshold while decreased cold withdrawal threshold, with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration (P<0.05, P<0.01). Moreover, JPTL down-regulated AQP1, AQP3, COX2, p-p38 MAPK, p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β, IL-6, TNF-α, and PGE2 in serum and/or inflammatory paw, but it had no significant effect on COX1 (P<0.05, P<0.01). ConclusionJPTL has anti-swelling and analgesic effects, and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway, which provides an experimental basis for the clinical application of JPTL.
9.Intervention of Osteoking in Rats with Myofascial Pain Syndrome
Xiaoxiao WANG ; Qun LI ; Zhixing HU ; Changting FANGLUO ; Ruirui MING ; Tengteng XU ; Chao YANG ; Wuqiong HOU ; Lili WANG ; Yini JIANG ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(24):19-29
ObjectiveTo clarify the intervention effect of Osteoking (OK) in rats with myofascial pain syndrome (MPS) and preliminarily explore the pharmacological mechanism of OK in relieving chronic pain from the perspective of anti-inflammatory disease. MethodThe 60 SD rats were divided into normal group, model group, low, medium, and high dose OK groups (0.66, 1.31, 2.63 mL·kg-1), and positive celecoxib group (21 mg·kg-1). The MPS rat model was established by beating combined with the centrifugal exercise method, and the OK and celecoxib were given at the same time. SMALGO paw pressure pain manometer detected the shock pain point tenderness threshold of rats, and the Von-Frey needle and acetone stimulation method detected the mechanical hyperalgesia threshold and cold hyperalgesia stimulation response respectively. Eight weeks and 10 weeks after modeling, the spontaneous discharge state and convulsion response of MPS rats were determined by electromyograph (EMG) instrument. The gait changes of MPS rats were detected using a CatWalk gait analyzer. The expression levels of interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), substance P (SP), and bradykinin (BK) were measured by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of nuclear transcription factor-κB (NF-κB) inhibiting protein α (IκBα), phosphorylates (p)- IκBα, NF-κB p65, and p-NF-κB p65 were detected in MPS rats by Western blot. The positive expression of p-NF-κB p65 was detected by immunofluorescence. ResultCompared with the normal group, the model group shows 100% positive rates for EMG signal and local convulsions response at both the 8th and 10th weeks. The tenderness threshold and mechanical hyperalgesia threshold are significantly reduced. Cold hyperalgesia score is significantly increased, and gait is abnormal. The expression levels of serum and trigger points IL-1β, TNF-α, SP, BK, p-IκBα, and p-NF-κB p65, as well as the positive expression intensity of p-NF-κB p65 are significantly increased (P<0.01). Compared with the model group, the positive rate of EMG detection and local convulsion response is significantly reduced in the medium and high dose OK groups (P<0.05). The tenderness threshold and mechanical hyperalgesia threshold increase significantly in the medium and high dose OK groups, and the cold hyperalgesia score is significantly reduced in the high dose OK group (P<0.01). The standing time, swing time, and walking period are significantly increased. The swing speed, maximum contact area, and maximum contact intensity are significantly decreased in the high dose OK group (P<0.05). Moreover, the protein expression levels of p-IκBα/IκBα and p-NF-κB p65/NF-κB p65 are significantly reduced in the medium and high dose OK groups (P<0.05,P<0.01). The positive expression intensity of p-NF-κB p65 is significantly decreased in the high dose OK group (P<0.01). ConclusionThe mechanism of OK in relieving the pain in trigger points of MPS and improving gait abnormalities is related to the downregulation of the NF-κB p65 inflammatory signaling pathway to reduce the expression of inflammatory factors and pain mediators in blood and trigger point tissue.