Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis

Objective Acute myeloid leukemia(AML)is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion.Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis.In this study,we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition.Methods Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls.A systematic analysis of clinical characteristics and prognostic factors was also conducted.Cell growth was assessed using the Cell Counting Kit-8(CCK-8)assay,and apoptosis and cell cycle progression were evaluated by flow cytometry.Moreover,RNA pull-down was performed to identify target microRNAs,and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets.Results Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival(OS)(hazard ratio:2.357;95%confidence interval 1.258–4.415).The circ_0012152 knockdown reduced cell growth,increased apoptosis,and inhibited cell cycle progression in AML cell lines.RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152.Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors.We suggested that miR-652-3p targeted SOX4,as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells.Conclusion Circ_0012152 is an independent poor prognostic factor for OS in AML,and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Factors Associated with Acute Respiratory Infections in Children Aged 0 - 5 Years in the Yénawa District of Cotonou (Benin) in 2023

Introduction: Acute respiratory infections remain one of the main causes of mortality in children aged 0 to 5. This work aimed to study the associated factors with the occurrence of acute respiratory infections in children 0 to 5 years old in Yénawa, Cotonou in 2023. Subjects and Method: It was an analytical cross-sectional study of children aged 0 - 5 years and their mothers in Yénawa, selected by four-degree random sampling. The sampling size, calculated using the Schwartz formula, was 126 children and 126 mothers. The dependent variable was the occurrence of acute respiratory infections. The independent variables were classified into four groups: socio-demographic and economic characteristics, behavioral factors, child-related factors, and environmental factors. Data collected by observation and questionnaire survey were analyzed using STATA version 15 software. Associated factors were investigated by bivariate analysis and multiple logistic regression, at the 5% significance level. Results: A total of 126 children aged 0 - 5 years and 126 mothers were surveyed, aged 23.5 (11 - 36) months and 30 (18 - 48) years respectively. The prevalence of acute respiratory infections was 74.60% (CI95% = 66.89 to 82.30). The associated factors were the mother’s age between 18 and 28 (OR = 10.77;CI95% = 1.89 to 61.27;p = 0.007), the use of charcoal/wood for cooking (OR = 7.36;IC = 1.99 to 27.10;p = 0.003)), children's poor personal hygiene (OR = 8.87;IC = 2.92 to 26.97;p 0.001)), and cohabitation with domestic animals (OR = 7.27;IC = 1.67 to 31.71;p = 0.015). Conclusion: Communicating with mothers about the factors identified will help reduce the prevalence of acute respiratory infections in children aged 0 to 5.

Evaluation of the Integrated Management Program for Acute Malnutrition in the Douentza Health District, Mopti Region, Mali

Introduction: Malnutrition is a major public health problem in Mali, despite the efforts of the government, its technical and financial partners. The aim of this study was to evaluate the integrated management program for acute malnutrition (IMPAM). Methodology: This was a descriptive cross-sectional study that took place from January to December 2020 in the Douentza health district. The study included anyone with at least one malnourished child aged 6 to 59 months in their care who agreed to take part in the study, community health center staff who had given their consent, and the URENI manager at the Douentza reference health center. Data collected via questionnaires were entered into Excel and then analyzed using Epi-Info version 7 software. Results: A total of 138 acutely malnourished children aged 6 - 59 months, including 71 girls (51.45%), 138 accompanying mothers and 11 health workers, were included in our case study. Among the malnourished, 54.34% were in the 12 - 23 months age group and 69.57% had the severe form. 93% of the mothers interviewed were satisfied with the care provided, and all the health staff interviewed stated that community conflicts had an impact on IMPAM’s activities. Cure rates were 81% in Moderate Outpatient Nutritional Recovery and Education Unit (URENAM), 84% in Severe Ambulatory Nutritional Recovery and Education Unit (URENAS) and 92% in Recovery and Intensive Nutritional Education Unit (URENI). Drop-out rates were 19% in URENAM, 16% in URENAS and 0% in URENI. The death rate was 8% in URENI and 0% in URENAM and URENAS. Conclusion: This study confirms the high prevalence of malnutrition in the district (10.54%). It also reveals that factors such as inter-community conflict and insecurity have seriously affected the IMPAM program.

The Role for AVE0991 (MAS-Receptor Angiotensin II (1-7) Agonist) in Reducing Cisplatin-Induced Acute Kidney Injury on C57BL/6 Mice

Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

High frequency of CD34+CD38-/low immature leukemia cells is correlated with unfavorable prognosis in acute myeloid leukemia

AIM To evaluate the importance of the CD34+CD38-cell population when compared to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to determine its correlations with leukemia characteristics and known prognostic factors, as well as with response to therapy and survival.METHODS Two hundred bone marrow samples were obtained at diagnosis from 200 consecutive patients with newly diagnosed acute myeloid leukemia(AML) were studied between September 2008 and December 2010 at our Institution(Hematology Department, Lyon, France). The CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach using 8 C panels and FACS CANTO and Diva software(BD Bioscience).RESULTS We analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at diagnosis, and investigated the prognostic value of the most immature CD34+CD38-population. Using a cut-off value of 1% of CD34+CD38-from total "bulk leukemic cells" we found that a high(> 1%) level of CD34+CD38-blasts at diagnosis was correlated with advanced age, adverse cytogenetics as well as with a lower rate of complete response after induction and shorter disease-free survival. In a multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells and the standardized cytogenetic and molecular risk subgroups, a percentage of CD34+CD38-leukemic cells > 1% was an independent predictor of DFS [HR = 2.8(1.02-7.73), P = 0.04] and OS [HR = 2.65(1.09-6.43), P = 0.03].CONCLUSION Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell analysis by multicolour flowcytometry at diagnosis provides useful prognostic information.

Regulation of ω-3 Fish Oil Emulsion on the SIRS during the Initial Stage of Severe Acute Pancreatitis

The aim of this study was to explore the effects of parenteral supplementation with ω-3 fish oil emulsion （Omegaven） on systemic inflammatory response syndrome （SIRS） during the initial stage of severe acute pancreatitis （SAP）. In a prospective, randomized and controlled trial, 60 patients with SAP were randomized either to treat with conventional therapy （Con group, n=30） or conventional therapy plus intravenous supplementation with ω-3 fish oil emulsion 0.2 g/kg every day （FO group, n=30）. The effects were analyzed by the SIRS-related indexes. The results showed that APACHE-Ⅱ scores in FO group were significantly lower, and the gap increased much farther after the 4th day than those in Con group （P〈0.05）. Fluid equilibrium time became shorter markedly in FO group than in Con group （5.1±2.2 days vs 8.4±2.3 days）. In FO group, SIRS scores were markedly decreased and the SIRS state vanished after the 4th day; Plasma level of TNF-α was significantly reduced, while IL-10 decreased markedly, most prominently between the 4th and 7th day, and the ratio of IL-10/TNF-α raised as compared with Con group （P〈0.05）. During the initial stage of SAP, parenteral supplementation with ω-3 fish oil emulsion could efficiently lower the magnitude and persistence time of the SIRS, markedly retrieve the unbalance of the pro-/anti-inflammatory cytokines, improve severe condition of illness and may provide a new way to regulate the SIRS.

Pseudogene HMGN2P46 as a microRNA sponge to regulate HMGN2 expression via competing for miR-590-3p in severe acute pancreatitis

HMGN2 have functions in inflammatory response.However,the role of HMGN2 in severe acute pancreatitis(SAP)remains unclear.Here,our study was to discuss the role and regulatory mechanism ofHMGN2 in SAP.In this study,the SAP cell model of AR42J was used to study the function and mechanism of HMGN2 in SAP.The protein expression in cells and serums were examined by western blot and ELISA assay.qPCR was used to test the transcriptional RNA level.Cell viability were examined by MTT assay.Luciferase assay was used to evaluate the interaction between gene and gene.Our results showed that HMGN2 was significantly upregulated in SAP patients.The database predicted and luciferase assay data indicated the HMGN2 was directly binding with miR-590-3p.ELISA,MTT and western blot experiments showed that the HMGN2 were promoted the cell proliferation,reduced the inflammation,and repressed the cell autophagy.Mechanism studies showed that the pseudogene HMGN2P46 level was positively correlated with HMGN2 and upregulated HMGN2 expression by competing for miR-590-3p in SAP.Taken together,all over these results showed upregulation of HMGN2 alleviates SAP,this process was regulated by HMGN2P46 competitively binding with miR-590-3p,which may provide a new insight for the treatment and intervention in SAP.Pseudogene HMGN2P46 was a miRNA sponge to regulate HMGN2 level by competing for miR-590-3p to alleviate the process of SAP.It provided a novel strategy for the diagnosis and treatment of severe acute pancreatitis.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).

NBASS-APS护理干预在全麻恢复期患者中的应用

目的研究以护士为基础、以麻醉医师和专科为指导的急性疼痛服务(NBASS-APS)模式护理干预对全麻恢复期患者的影响。方法选取郑州大学第一附属医院2020年11月至2022年11月麻醉复苏室(PACU)118例全麻恢复期患者作为研究对象,采用随机信封法分为对照组(59例)、观察组(59例),对照组接受常规护理模式,观察组在此基础上接受NBASS-APS模式护理干预。比较两组术后恢复指标、并发症(寒战、躁动)发生率、疼痛护理满意度及不同时间点视觉模拟评分(VAS)、负性情绪[Beck抑郁量表21项(BDI-21)、Beck焦虑量表(BAI)]。结果观察组拔管时间、苏醒时间、出PACU时间、肠道功能恢复时间较对照组短(P<0.05);观察组寒战、躁动发生率(1.69%、5.08%)均低于对照组(15.25%、20.34%)(P<0.05);苏醒60 min后观察组VAS评分较对照组降低(P<0.05);苏醒60 min后观察组BDI-21、BAI评分较对照组降低(P<0.05);观察组疼痛护理满意度(96.61%)较对照组(79.66%)高(P<0.05)。结论NBASS-APS模式的护理干预能预防寒战、躁动发生,有利于减轻全麻恢复期患者疼痛,改善患者负性情绪,促进患者康复,提升患者疼痛护理满意度。

PPAR -γ激动剂对 LPS 诱导的小鼠 ARDS 肺泡上皮钠通道-γ亚基的调控

目的：探讨过氧化物酶增殖体活化受体-γ（ PPAR-γ）激动剂对LPS诱导的小鼠ARDS的保护作用及其对肺泡上皮细胞钠通道-γ亚基（ ENaC-γ）的调控作用。方法40只雄性BALB/C小鼠随机分为对照组（ Control组）、模型组（ LPS组）、罗格列酮治疗组（ RGZ组，LPS＋罗格列酮）及GW9662干预组（ GW9662组，LPS＋GW9662＋罗格列酮），每组10只。处理后收集相关标本，ELISA测定肺泡灌洗液（ BALF）中IL-1β和TNF-α水平。肺组织湿/干比（ W/D）测定肺水肿程度。 HE染色观察肺组织病理变化并进行肺组织损伤评分。用免疫组织化学法和Western blot测定肺组织ENaC-γ蛋白的表达。 RT-PCR测定ENaC-γmRNA的表达。结果与Control组比较，LPS组、RGZ组和GW9662组中IL-1β和TNF-α水平、W/D值、HE染色肺组织损伤程度及评分明显升高（ P＜0．05）；与LPS组比较，RGZ组各指标水平及肺损伤评分明显下降（P＜0．05），但LPS组和GW9662组比较差异无统计学意义（P＞0．05）。 LPS造模后，LPS组（210±15IOD，0．18±0．02，0．22±0．04）、RGZ组（450±30IOD，0．43±0．03，0．45±0．03）、GW9662组（235±35IOD，0．21±0．03，0．25±0．02）肺组织ENaC-γ蛋白和mRNA的表达明显低于Control组（600±25IOD，0．64±0．01，0．67±0．02，P＜0．05），RGZ组与LPS组和GW9662比较差异有统计学意义（P＜0．05），但LPS组和GW9662组比较差异无统计学意义（P＞0．05）。结论 PPAR-γ受体激动剂可能从转录水平上调肺泡ENaC-γ的表达，从而减轻LPS诱导的小鼠ARDS肺水肿程度，发挥保护性作用。

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory effects.In this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus macaques.We found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP.Therefore,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.

血必净对急性肾衰竭患者 IL -6和 IL -8的影响

目的：观察血必净注射液在急性肾衰竭（ ARF ）患者救治中对血清白细胞介素-6（IL-6）、白细胞介素-8（IL-8）的影响，进一步揭示血必净治疗急性肾衰竭的临床意义。方法选择2010-02～2012-12本院收治的73例ARF患者，随机分为两组，对照组35例，采用单纯西医综合治疗；治疗组38例，在单纯西医综合治疗基础上联合血必净治疗。观察两组患者治疗前及治疗1周、2周血浆IL-6、IL-8浓度。结果与对照组比较，治疗组治疗1周IL-6、IL-8浓度明显下降（P＜0．05），治疗2周IL-6、IL-8浓度下降更明显（P＜0．01）；所有患者治疗后IL-6、IL-8浓度较治疗前明显下降（P＜0．05）。结论在单纯西医综合治疗基础上联用血必净注射液，能更有效地降低ARF患者的炎症反应水平，提高治愈率，降低病死率。

Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats

AIM To explore the kinetic changes in plasma D(-)- lactate and lipopolyssccharide(LPS)levels,and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/ reperfusion,burn,and acute necrotizing pancreatitis (ANP). METHODS Three models were developed in rats:① gut ischemia/ reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion;② severe burn injury created by 30% of total body surface area(TBSA)full-thickness scald burn;and ③ ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic- spectrophotometric method and limulus amebocyte lysate (LAL)test kit,respectively.Tissue samples of intestine were taken for histological analysis. RESULTS One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)- lactate and LPS levels,and there was a significant correlation between the plasma D(-)-lactate and LPS(r =0.719,P<0.05).The plasma concentrations of D(-)- lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r = 0.877,P < 0.01).D(-)-lactate and LPS levels elevated significantly at 2h after ANP,with a similar significant correlation between the two levels(r = 0.798, P < 0.01 ).The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood.The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.

Silencing miRNA-324-3p protects against cerebral ischemic injury via regulation of the GATA2/A1R axis

Previous studies have suggested that miR-324-3p is related to the pathophysiology of cerebral ischemia,but the mechanism underlying this relationship is unclea r.In this study,we found that miR-324-3p expression was decreased in patients with acute ischemic stroke and in in vitro and in vivo models of ischemic stro ke.miR-324-3p agomir potentiated ischemic brain damage in rats subjected to middle cerebral artery occlusion,as indicated by increased infarct volumes and cell apoptosis rates and greater neurological deficits.In a PC12 cell oxygen-glucose deprivation/reoxygenation model,a miR-324-3 p mimic decreased cell viability and expression of the anti-apoptotic protein BCL2 and increased expression of the pro-apoptotic protein BAX and rates of cell apoptosis,whereas treatment with a miR-324-3p inhibitor had the opposite effects.Silencing miR-324-3p increased adenosine A1 receptor(A1R)expression thro ugh regulation of GATA binding protein 2(GATA2).These findings suggest that silencing miR-324-3p reduces ischemic brain damage via the GATA2/A1R axis.

Correlation between serum PCT, IL-6 and CRP levels and pulmonary ventilation function in AECOPD patients

Objective: To investigate the correlation of serum calcitonin (PCT), interleukin -6 (IL-6), C reactive protein (CRP) and pulmonary ventilation function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: 70 patients with AECOPD in our hospital from May 2017 to May 2018 were selected to be included in the case group, and 70 healthy persons in the same period were selected as the control group. The serum levels of PCT, IL-6, CRP and lung function were compared between the two groups, and the relationship between the serum levels of PCT, IL-6 and CRP and the pulmonary ventilation function of the patients was analyzed. Results: the levels of PCT, IL-6 and CRP in the case group were significantly higher than those in the control group. The difference was statistically significant (P < 0.05), and the FEV1, FEV1/FVC and FEV1% in the case group were significantly lower than those in the control group (P < 0.05), and the difference of PCT, IL-6 and CRP was significant between the patients with different pulmonary function levels, and the statistics were statistically significant. The study significance (P < 0.05), and the level of PCT, IL-6 and CRP increased gradually with the increase of lung function grade, and the level of PCT, IL-6 and CRP in AECOPD patients were negatively correlated with FEV1, FEV1/FVC and FEV1%, and the difference was statistically significant (P < 0.05). Conclusion: the serum levels of PCT, IL-6 and CRP in patients with AECOPD are abnormal increased and are closely related to the pulmonary ventilation function of the patients, which can be used as an important indicator of the monitoring of the patient's condition in AECOPD.

The Stress of COVID-19:Playing Havoc with the Hormones-A Review

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has affected millions of people across the world engendering an unprecedented pandemic.Coronavirus disease(COVID)-19 can present asymptomatic or in the form of the acute respiratory syndrome,viral pneumonia,or sepsis.Due to the novelty of the disease,the endocrine manifestations are not fully understood.It becomes indispensable to address the underlying endocrine disruptions contributing to the severe form of illness and thereby increasing the mortality.We discuss here the SARS-CoV-2 virus and endocrine reverberations based on the research with structurally similar SARS-COV-1.SARS-CoV-2 enters the body via its attachment to the angiotensin-converting enzyme 2(ACE2)receptors.Apart from lungs,ACE2 expression on various organs can lead to endocrine perturbations.In COVID-19 infection,pre-existing endocrine disorders warrant cautious management and may require replacement therapy.COVID-19 and its repercussions on hormones are discussed extensively in this review.

Activation of the corticotropin-releasing factor receptor from the basolateral or central amygdala modulates nociception in guinea pigs

Corticotropin-releasing factor (CRF) is a peptide that is released from the hypothalamus into widespread areas of the brain. Evidence has suggested that CRF is involved as a neuromodulator outside of the hypothalamic-pituitary-adrenal axis, playing an important role in fear, anxiety, depression and pain modulation. Our previous report demonstrated that CRF receptor activation in basolateral (BLA) or central nuclei of the amygdala (CeA) produces innate fear in guinea pigs. Inhibition of these receptors via administration of α-helical CRF9-41 (a nonspecific antagonist) into the CeA or BLA decreased innate fear behavior [1]. Additionally, there is strong evidence that emotional behavior and nociception can be modulated simultaneously. The present study was conducted to investigate the involvement of the CRF receptors of the BLA or CeA in nociception in guinea pigs. Guinea pigs were treated with CRF and α-helical CRF>9-41> in three different doses or injected with α-helical CRF9-41 preceded by CRF into the BLA or CeA, and they were evaluated using the hot plate test. Our findings indicated that activation of CRF receptors in the BLA and in the CeA promoted antinociception, and this effect was reversed by preadministration of α-helical CRF9-41 in the same area. The treatment with α-helical CRF>9-41> per se into the BLA and CeA did not alter nociception. Thus, nociception modulation occurs in a phasic manner, whereas defensive behavior can occur tonically because the α-helical CRF9-41 did not cause any modification on the index of analgesia in the hot plate test but did reduce innate fear behavior [1].

齐拉西酮注射液联合解郁丸治疗精神分裂症急性期激越症状的效果观察

目的探讨齐拉西酮注射液联合解郁丸治疗精神分裂症急性期激越症状的临床效果。方法选取2019年6月至2020年6月我院收治的120例具有急性期激越症状的精神分裂症患者,随机分为两组各60例。对照组给予齐拉西酮注射液治疗,观察组给予齐拉西酮注射液联合解郁丸治疗。比较两组的急性期激越症状缓解效果、PANSS-EC评分及不良反应。结果观察组的急性期激越症状总缓解率为95.00%,高于对照组的83.33%(P<0.05)。治疗后,两组的PANSS-EC评分均较治疗前降低(P<0.05),且观察组的PANSS-EC评分低于对照组(P<0.05)。观察组的不良反应总发生率为15.00%,低于对照组的30.00%(P<0.05)。结论齐拉西酮注射液联合解郁丸治疗精神分裂症急性期激越症状效果显著,安全性高。

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis

Background:Acute myeloid leukemia(AML)is a malignant hematological disease,originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation.New reagents or biologicals for the treatment of AML are urgently needed,and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis.This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells(BMSCs)on AML cells as well as the underlying microRNA(miRNA)-mediated mechanisms.Methods:Exosomes were isolated using a precipitation method,followed by validation using marker protein expression and nanoparticle tracking analysis.Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction(qPCR).Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method,and cell cycle progression and apoptosis were detected by flow cytometry.Functional gene expression was analyzed by qPCR and Western blotting(WB).Significant differences were determined using Student’s t test or analysis of variance.Results:BMSCs-derived exosomes effectively suppressed cell proliferation(both P<0.0001 at 10 and 20μg/mL)and cell cycle progression(P<0.01 at G0-G1 stage),and also significantly enhanced cell apoptosis(P<0.001)in KG-1a cells.There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes(P<0.05).Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation(both P<0.0001 vs.normal KG-1a cell[NC]at 48 and 72 h).KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4(P<0.001 vs.NC by qPCR and P<0.0001 vs.NC by WB),which is associated with the progression of various cancers.This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p(P<0.0001 vs.NC by WB).Conclusions:BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells,likely acting through hsa-miR-124-5p.Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.