[Efficacy and safety of first-line treatment with anti-CD38 monoclonal antibody-based regimen for primary plasma cell leukemia].

Objective: To analyze the efficacy and safety of first-line treatment with an anti-CD38 monoclonal antibody regimen for primary plasma cell leukemia (pPCL). Methods: Patients diagnosed with pPCL from December 1st, 2018 to July 26th, 2023, receiving first-line treatment of anti-CD38 monoclonal antibody-based regimens across multiple centers including Peking University People's Hospital, Fuxing Hospital of Capital Medical University, Qingdao Municipal Hospital, Shengjing Hospital of China Medical University, Handan Central Hospital, the First Affiliated Hospital of Harbin Medical University, the Fourth Hospital of Hebei Medical University and General Hospital of Ningxia Medical University were consecutively included. A total of 24 pPCL patients were included with thirteen being male and eleven being female. The median age [M(Q1, Q3)] was 60 (57, 70) years. Patients were grouped according to peripheral blood plasma cell (PBPC) percentage [5%-19% (n=14) vs ≥20% (n=10)]. Last follow-up date was September 26th, 2023. The median follow-up period was 9.1 (4.2, 15.5) months. Patients' data related with clinical baseline characteristics, efficacy, survival and safety were retrospectively collected. Cox proportional hazards regression model was used to analyze risk factors associated with survival. Results: Among 24 pPCL patients, 16 (66.7%) patients had anemia at diagnosis, 13(54.2%) patients had thrombocytopenia, 8 (33.3%) patients had a baseline estimated glomerular filtration rate (eGFR)<40 ml·min-1·(1.73m2)-1, 13 (54.2%) patients had elevated lactate dehydrogenase (LDH) levels. The median PBPC percentage was 16% (8%, 26%) . Fluorescence in situ hybridization testing indicated that patients harboring 17p deletion, t(4;14) or t(14;16) were 6 (25.0%), 4 (16.7%) and 4 (16.7%), respectively. The overall response rate was 83.3% (20/24). The median progression-free survival (PFS) was 20.5 (95%CI: 15.8-25.2) months, and the median overall survival (OS) was not reached. Estimated 1-year and 2-year PFS and OS rates were 75.0% and 89.1%, 37.5% and 53.4%, respectively. The median PFS and OS for patients with PBPC percentages 5%-19% and≥20% were not reached and 20.5 (95%CI:15.7-25.3) months, 17.8 months and not reached, respectively. There was no significant statistical difference of PFS and OS between two groups (all P>0.05). Multivariate Cox regression analysis showed that 1p32 deletion was the risk factor associated with PFS (HR=7.7, 95%CI: 1.1-54.9, P=0.043). Seventeen patients (70.8%) developed grade 3-4 hematologic toxicities. Twelve patients (50.0%) developed grade 3-4 thrombocytopenia. Sixteen patients (66.7%) developed infection. All hematologic toxicities and infections were improved after supportive treatment. Conclusion: First-line treatment with anti-CD38 monoclonal antibody-based therapy for pPCL is effective and safe.

[Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant].

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

[An arthroscopic "inlay" Bristow procedure with suture button fixation: Surgical technique and radiology evaluation].

OBJECTIVE: To introduce an arthroscopic "inlay" Bristow procedure based on the Mortise-Tenon joint structure concept using suture button fixation, and to evaluate its clinical and radiology results postoperatively with a minimal 3-year follow-up. METHODS: A total of 56 patients who received arthroscopic "inlay" Bristow procedure with suture button fixation between June 2015 to June 2016 were eventually enrolled in this study. Radiological assessment on the 3D CT scan was performed preoperatively, immediately after operation, and postoperatively at the end of 3 months, 6 months and the final follow-up. Complications postoperatively were also recorded. RESULTS: A total of 56 patients were finally included in this study. The mean follow-up time was (36.1±3.7) months. Coracoid grafts (middle point) were positioned at about 4 o'clock (123.8°±12.3°) in the En-face view. In the axial view, 95% (53/56) of the grafts positioning were measured as flush, 5% (3/56) as medial. Bone union rate was 96.4% at the final follow-up. At the end of 3 months, 6 months, and the final follow-up, the length of the coracoid graft was 96.9%±4.9%, 91.9%±6.2%, and 91.6%±6.6% of the immediate postoperative length, respectively. Compared with the immediate postoperative length, the length measured at the end of 3 months shortened not significantly (t=2.12, P > 0.05). The coracoid graft shortened more pronouncedly 6 months postoperatively (t=4.98, P < 0.05) and then remained almost constant over time (t=-0.75, P > 0.05), with all grafted coracoid graft retaining more than 90% of their initial length by the 3-year follow-up. And new bone formation at the junction between the coracoid graft and glenoid neck in the axial view were obviously noted in 25 cases. The quantitative evaluation showed that the glenoid area in En-face view was significantly increased at the final follow-up than that immediately after surgery [(9.72±1.22) cm2 vs. (9.42±1.11) cm2]. No degenerative changes were noted on CT images in all the patients at the final follow-up. CONCLUSION: This study reported a series of "inlay" Bristow procedure with suture button fixation for recurrent shoulder dislocation, providing satisfactory union rate and excellent graft positioning. And using suture button fixation instead of screw can reduce osteolysis and complications related to hardware implantation. Moreover, the bone remodeling between the coracoid process and glenoid could be beneficial to restoring the anterior stability of shoulder joint in a long term follow-up.

Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p.

The article "Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p, by Y. Mu, W.-J. Liu, L.-Y. Bie, X.-Q. Mu, Y.-Q. Zhao, published in Eur Rev Med Pharmacol Sci 2021; 25 (1): 145-153-DOI: 10.26355/eurrev_202101_24378-PMID: 33506902" has been withdrawn from the authors since the design of the manuscript was not rigorous enough (there were some flaws in some experiments). The authors explain that they will perform further experiments. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/24378.

[The study of the association between lung cancer screening and smoking behavior change].

The smoking cessation rate of 1 314 people at high risk of lung cancer in the area of lung cancer screening and early diagnosis and early treatment in Sichuan Province increased from 22.37% at baseline to 41.78% after screening (χ²=227.97, P<0.001), and the smoking amount of persistent smokers decreased from 20 cigarettes per day to 15 cigarettes per day (t=11.76, P<0.001). Those with positive results in lung cancer screening were more likely to quit smoking or continue to quit smoking. Male, younger age or lower education level would increase the risk of continuous smoking or relapse (P<0.05).

Blocking VRK2 suppresses pulmonary adenocarcinoma progression via ERK1/2/AKT signal pathway by targeting miR-145-5p.

OBJECTIVE: The incidence of pulmonary adenocarcinoma locates first in all the malignant tumors in the world. At present, there are many diagnostic methods for pulmonary adenocarcinoma, but there are a few methods that are mature or have ideal application prospects. We aim to explore the role of VRK2 in the occurrence and development of pulmonary adenocarcinoma and its possible regulatory mechanism. PATIENTS AND METHODS: Western blot and qRT-PCR were performed to assess the expression of VRK2. Flow cytometry, Western blot, and Caspase-3 colorimetric assay Kit were used to evaluate the apoptosis level. The proliferation, migration, and invasion ability were measured via cell cycle assay, wound healing, and transwell invasion assay. Luciferase assay verified the relationship between VRK2 and miR-145-5p. The effect of FGD5-AS1 on tumorigenesis of glioma was detected by the xenograft nude mice model. RESULTS: VRK2 was significantly increased in tumor tissues and cell lines. Loss of VRK2 promoted apoptosis level and inhibited the proliferation, migration, and invasion in A549 cells via regulating the ERK1/2/AKT signal pathway. Luciferase assay reported that VRK2 could bind with miR-145-5p. The level of miR-145-5p was negatively correlated with the expression of VRK2 and involved in VRK2 regulating tumor progression. The tumor growth assay showed that the silencing of VRK2 inhibited tumorigenesis with the inactivating ERK1/2/AKT pathway. CONCLUSIONS: Knockdown of VRK2 inhibited the development of pulmonary adenocarcinoma via regulating the ERK1/2/AKT signal pathway by targeting miR-145-5p, which providing some novel experimental basis for clinical treatment of pulmonary adenocarcinoma.

[Orthopedic treatment of musculoskeletal disorders in hemophilic patients].

Objective: To study the orthopedic treatment strategy for hemophilia complicated with musculoskeletal disorders as well as the peri-operative consumption of clotting factor. Methods: Total 338 orthopedic surgeries were performed for 261 patients, average age of 30.6 y (6-65 y) , with hemophilia between January 1996 and December 2019 at our institute. Two hundred and twenty-six patients presented with bleeds within the joints. Sixty-one patients presented with intramuscular bleeds, 45 presented with hemophilic pseudotumors, and six presented with miscellaneous complaints. Strategy of clotting factor replacement therapy was designed as per differences in the level of the operation procedure. Information regarding clinical manifestation, operative strategy, clotting factor consumption, and re-operation for complications was retrospectively recorded. The costs for multiple joint procedure and single joint procedure were studied. Results: We found that 270 of the 338 surgical procedures were major surgical procedures (79.9%) . There were 203 procedures of joint arthroplasty (60%) . Fourteen patients underwent reoperations for local recurrence (4.2%) . The average factor Ⅷ consumption before the surgery was 44.4 ± 8.1 IU/kg. The average FⅧ consumption within postoperative 2 weeks was 40 962 IU (647±177 IU/kg) . Seven type A hemophilic patients developed F Ⅷ inhibitor following the surgical procedure, with an average level of 13.7±11.2 BU/mL. Sixty-eight patients underwent multiple joint procedures under one anesthesia session (26%) . There was no significant difference in the factor consumption between the multiple joint procedure and single joint procedure. Conclusions: Surgical treatment was found to be effective for hemophilic arthropathy and lesion of the musculoskeletal apparatus, with the clotting factor replacement therapy. Multiple joint procedures under one anesthesia were more cost effective for patients with hemophilia, with less factor consumption than staged single joint procedure.

MicroRNA-323-3p inhibits oxidative stress and apoptosis after myocardial infarction by targeting TGF-ß2/JNK pathway.

OBJECTIVE: Myocardial infarction (MI), which causes irreversible damage and loss of cardiomyocytes, is the most important cause of death in the world. MicroRNA is an important regulator of physiological and pathological activities of cardiovascular system. The aim of this research was to study the effect of microRNA-323-3p (miR-323-3p) on MI and its underlying mechanisms of action. MATERIALS AND METHODS: A rat model of MI was established to measure the expression of miR-323-3p, Bax, Bcl-2, SOD1, and SOD2 in ischemic myocardial tissue, and the cardiac function of rats were tested at seventh day after MI. H9c2 cells were divided into control group, miRNA negative control (NC) transfection group, miR-323-3p mimic (miR-323-3p min) transfection group, and then, treated with H2O2. Oxidative stress and apoptosis of H9c2 cells were observed by Western blot, Real Time-Polymerase Chain Reaction (RT-PCR), flow cytometry, SOD activity assay, TUNEL staining, DHR dye assay, etc. RESULTS: The level of miR-323-3p was decreased in ischemic myocardium, as well as H2O2-treated H9c2 cells. MiR-323-3p overexpression greatly decreased the level of Bax and increased the levels of SOD1, SOD2, and Bcl-2. After treated with miR-323-3p mimic, TUNEL positive cells were greatly reduced, and apoptosis rate of H9c2 cells was greatly decreased. Moreover, SOD levels significantly increased, while ROS production decreased after treatment of miR-323-3p. After intravenous injection of miR-323-3p agomir in rats with MI, the cardiac function of the rats was significantly improved. Western blot and Luciferase reporter gene experiments illustrated that miR-323-3p acts by targeting TGF-ß2. CONCLUSIONS: MiR-323-3p was downregulated in ischemic myocardium and H2O2-treated H9c2 cells, and miR-323-3p overexpression reduced oxidative stress and apoptosis of cardiomyocytes. The protective function was achieved via regulation of TGF-ß2/JNK pathway.

[Diagnostic value of heparin-binding protein in patients with silicosis complicated by severe infection].

Objective: To explore the application value of heparin binding protein (HBP) in the diagnosis of severe infection in patients with silicosis. Methods: A prospective study was conducted on 150 patients with silicosis in the pneumoconiosis department of the General Hospital of Xuzhou Mining Group from January 2017 to March 2018. Among them, 100 were severely infected with silicosis and 50 were non-infected with silicosis. 30 patients were selected in the same period of physical examination as the control group. HBP, C-reactive protein (CRP) , procalcitonin(PCT) , white blood cell count (WBC) , neutrophil percentage, and absolute neutrophil count(ANC) were detected in all participants. Using the receiver operating characteristic curve(ROC) to analyze the diagnostic value of indicator above in patients with different stages of severe silicosis infection. Results: Plasma HBP levels in patients with severely infected silicosis group[(50.39±35.64) ng/ml] were higher than those in the non-infected group[(10.71±1.47) ng/ml] and the control group[(9.24±1.83) ng/ml] (P<0.05) , and with the increase of silicosis stages, there is an increasing trend (P<0.05). The ROC curve showed that the AUC of HBP in the patients with severe silicosis in the first, second, and third stages were 0.932, 0.977, and 0.964, which were higher than those of WBC, CRP, and PCT. Correlation analysis showed that HBP was positively correlated with WBC, CRP and PCT (r=0.711, 0.359, 0.729, P<0.01). Conclusion: HBP has high diagnostic efficacy in the diagnosis of severe infections in patients with silicosis, which may become a clinical screening indicator for severe infections in patients with silicosis and an auxiliary examination indicator for the stage of silicosis patients.

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial.

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

[Analysis of the level of the core knowledge and related factors of cancer prevention and treatment in the upper gastrointestinal cancer screening area of Sichuan Province in 2018].

Objective: To investigate the level of the core knowledge and related factors of cancer prevention and treatment among residents in the upper gastrointestinal cancer screening areas of Sichuan Province in 2018. Methods: From April to May 2018, a total of 1 386 residents from Chaotian District of Guangyuan, Enyang District of Bazhong, Nanjiang County of Bazhong, Cangxi County of Guangyuan, Shehong County of Suining, Yilong County of Nanchong, Xichong County of Nanchong and Xuanhan County of Dazhou were recruited in this study. A questionnaire survey was conducted to collect basic demographic characteristics and the knowledge of cancer prevention and treatment. The level of the core knowledge of cancer prevention and treatment of different population was analyzed. A multivariate linear regression model was performed to analyze the related factors. Results: In total, 80.9% (1 120) of all subjects was 25-64 years old and 48.0% (665) were male. The total number of questions answered by the subjects was 18 018, of which 12 147 were known, and the overall awareness rate among the respondents was 67.42%. The female respondents, respondentsaged 65 years old and over, with junior college education or above, and worked in government institutions had a good performance of the core knowledge (P<0.05), about 70.11% (6 571/9 373), 69.23% (387/559), 76.05% (6 327/8 320), and 77.09% (5 602/7 267) respectively. The results of multivariate linear regression showed that the older the age [ß=0.871 (95%CI: 0.623-1.119)], the higher the educational level [ß=0.741 (95%CI: 0.540-0.943)], the more questions respondents could know; compared with the workers in government organization and institution, workers in enterprise [ß=-2.913 (95%CI:-3.499--2.327)], farming workers [ß=-0.635 (95%CI:-1.175--0.095)] and other occupation people [ß=-1.126 (95%CI:-1.663--0.589)] could know fewer questions. Conclusion: In 2018, the level of the core knowledge of cancer prevention and treatment among residents in upper gastrointestinal cancer screening areas of Sichuan Province was relatively high. Age, education level and occupation were relevant factors.

[Advances in the diagnostic pathological features of precancerous lesions of hepatocellular carcinoma].

The occurrence of hepatocellular carcinoma (HCC) is a multistep development process through precancerous lesions. A precancerous lesion of HCC is classified into hepatocyte dysplasia at the cytological level and dysplastic nodules at the histological level, and the corresponding lesion subtypes have different risks of canceration. Pathology is the "gold standard" for the diagnosis of early stage HCC and its precancerous lesions. However, it also faces many difficulties and challenges, such as the accumulation of experience in the pathological diagnosis, the understanding and grasp of key points of histopathological diagnosis and differential diagnosis, the combination application of immune and molecular diagnostic markers, and many others. This article briefly discusses the key points of pathological features and differential diagnosis of precancerous lesions of HCC.

[Ganglioneuroma in poststyloid space removed under endoscope through transoral approach: a case report].

Parapharyngeal space refers to the potential space under skull base between masticatory muscles and pharyngeal muscles, ranging from skull base at the top to hyoid bone at the bottom. The outer lateral wall consists of medial pterygoid muscle, deep parotid lobe and lower jawbone, lateral pharyngeal wall, medial pterygoid, deep lobe of parotid gland and mandible constitute the lateral wall, lateral pharyngeal wall forms medial wall, and prevertebral fascia constitutes the posterior wall, generally forming an inverted pyramid lacuna. Parapharyngeal space is divided into prestyloid space and poststyloid space by stylopharygeal fascia. Prestyloid space is relatively small and contains levator veli palatinetensor veli palatine, branches of maxillary artery, mandibular nerve and its branches. Poststyloid space is relatively large. It includes internal jugular vein, internal carotid artery, posterior cranial nerves, etc. Poststyloid space tumors are relatively rare. In this report, a case of ganglioneuroma wrapping right internal carotid artery is described, which is resected through oral approach.

MEG3 inhibits cell proliferation, invasion and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma.

OBJECTIVE: Dysregulation of long non-coding RNAs (lncRNAs) is associated with human carcinogenesis. The aim of the study is to explore the biological functions of MEG3 expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: QRT-PCR analysis was performed to assess the expression of MEG3 in 35 pairs of LSCC tissues and adjacent non-cancerous tissues. Cell proliferation, cell migration, and cell invasion capacities were determined by CCK8 assay and transwell assay in Hep-2 cell. QRT-PCR and Western blot analysis were applied to detect the relative expression of Twist1, E-cadherin and Vimentin in Hep-2 cells. RESULTS: In the study, our results showed that MEG3 expression was significantly lower in tumor tissues compared with that in adjacent non-cancerous tissues. Lower MEG3 expression was significantly associated with lymph node metastasis and advanced TNM stage of patients. Knockdown of MEG3 significantly promotes cell proliferation, cell migration, cell invasion and Epithelial-Mesenchymal Transition (EMT) process by upregulating Twist1 and Vimentin expression and reducing E-cadherin expression in Hep-2 cell. Conversely, upregulation of MEG3 had the inhibiting effects in Hep-2 cell. CONCLUSIONS: These results suggested that MEG3 may serve as a novel potentially therapeutic target for LSCC treatment.

MiR-146a regulates the development of ulcerative colitis via mediating the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE: To study the effect of micro ribonucleic acid (miR)-146a on the development of ulcerative colitis (UC) and to explore its regulatory effect on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB) signaling pathways. MATERIALS AND METHODS: The UC model in rats was established using 2,4,6-trinitrobenzenesulfonic acid (TNBS)/ethanol. A total of 30 male rats were randomly divided into control group, model group and miR-146a inhibitor group, with 10 rats in each group. The disease activity index (DAI) and the macroscopic score of colonic mucosa were measured in each rat. MiR-146a expression in rat intestinal tissues was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Serum levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in rats were detected via enzyme-linked immunosorbent assay (ELISA). Additionally, Western blotting assay was performed to detect protein levels of TLR4, MyD88, and NF-κB in rat intestinal tissues. RESULTS: Compared with those in control group, rats in model group had notably increased DAI, inflammation score, upregulated expression levels of TLR4, MyD88, NF-κB, and miR-146a, as well as increased serum levels of IL-1ß and TNF-α. However, rats in miR-146a inhibitor group exhibited substantially decreased DAI, inflammation score, lowered content of IL-1ß and TNF-α and levels of TLR4, MyD88, and NF-κB compared with those in model group. CONCLUSIONS: We found that miR-146a inhibitor alleviates UC by reducing the release of inflammatory factors through suppressing the TLR4/MyD88/NF-κB signaling pathway.

Upregulation of miR-504-3p is associated with favorable prognosis of acute myeloid leukemia and may serve as a tumor suppressor by targeting MTHFD2.

OBJECTIVE: Deregulated expression of miRNAs contributes to the development of acute myeloid leukemia (AML). miR-504-3p, one of these miRNAs, has been found have upregulated expression in various human malignancies. Our present study aimed to detect the expression of miR-504-3p and its biological effect in AML. PATIENTS AND METHODS: Real-time quantitative PCR was applied to evaluate the expression level of miR-504-3p in AML cell lines and the serum from AML cases. The correlations between miR-504-3p and AML patients' clinicopathological characteristics, as well as AML patients' overall survival, were statistically assessed. Moreover, we investigated the effect of miR-504-3p knockdown on AML cells by CCK-8, Transwell assays and flow cytometry, in vitro. The Western blot, RT-PCR and luciferase reporter assay were performed to evaluate the relationship between miR-504-3p and its downstream target genes. Finally, the biological function of MTHFD2 was also analyzed. RESULTS: The expression levels of miR-504-3p were significantly down-regulated in the serum of AML patients and cell lines, and its low expression was positively associated with advanced clinical stages and poor prognosis of AML patients. Functional assays indicated that overexpression of miR-504-3p leads to AML cell growth arrest, invasion and migration inhibition, and elevated rates of apoptosis. We also found that miR-504-3p regulated the expression of MTHFD2 by binding to its 3'-UTR, and knockdown of MTHFD2 significantly suppressed AML cells proliferation, migration and invasion, and promoted apoptosis. CONCLUSIONS: Our findings provide important evidence that supports the role of miR-504-3p as a tumor suppressor in AML via the inhibition of MTHFD2 expression.