[Objective] To analyse and predict the tendencies of using erythrocyte blood in Changsha based on the autoregressive integrated moving average (ARIMA) model, long short-term memory (LSTM) and ARIMA-LSTM combination model, so as to provide reliable basis for designing a feasible and effective blood inventory management strategy. [Methods] The data of erythrocyte usage from hospitals in Changsha between January 2012 and December 2023 were collected, and ARIMA model, LSTM model and ARIMA-LSTM combination model were established. The actual erythrocyte consumption from January to May 2024 were used to assess and verify the prediction effect of the models. The extrapolation prediction accuracy of the models were tested using two evaluation indicators: mean absolute percentage error (MAPE) and root mean square error (RMSE), and then the prediction performance of the model was compared. [Results] The RMSE of LSTM model, optimal model ARIMA(1,1,1)(1,1,1)12 and ARIMA-LSTM combination model were respectively 5 206.66, 3 096.43 and 2 745.75, and the MAPE were 18.78%,11.54% and 9.76% respectively, which indicated that the ARIMA-LSTM combination model was more accurate than the ARIMA model and LSTM model, and the prediction results was basically consistent with the actual situation. [Conclusion] The ARIMA-LSTM model can better predict the clinical erythrocyte consumption in Changsha in the short term.

Objective:To explore mechanism of regulation of proliferation,migration,invasion and expressions of immune factors of ovarian cancer SKOV3 cells by circSKA3/miR-3163/disintegrin-metalloproteinase 9(ADAM9)gene axis.Methods:qRT-PCR was used to detect circSKA3 and miR-3163 expressions in ovarian cancer tissues and paracancerous tissues.Western blot was used to detect ADAM9 protein level in tissues.SKOV3 cells were selected for cell experiment in vitro,and divided into sh-NC group,sh-circSKA3 group,miR-NC group,miR-3163 group,sh-circSKA3+anti-miR-3163 group,sh-circSKA3+pcDNA-ADAM9 group.circSKA3 and miR-3163 expressions in SKOV3 cells were detected by qRT-PCR.CCK-8,scratch test and Transwell were used to detect cell proliferation activity,migration and invasion ability.ELISA was used to detect expressions of TNF-α,IL-6 and IL-10.Double luciferase report experiment verified targeting relationship between circSKA3 with miR-3163,miR-3163 and ADAM9.Western blot was used to detect levels of ADAM9,matrix metalloproteinase-2(MMP-2)and MMP-9 in SKOV3 cells.Results:Com-pared with paracancerous tissues,circ-SKA3 and ADAM9 expressions were increased,and miR-3163 expression was decreased in ovarian cancer tissues(P<0.05).Compared with sh-NC group/miR-NC group,sh-circSKA3 group/miR-3163 group showed decreased cell proliferative activity and healing rate,decreased number of invasive cells,MMP-2,MMP-9 proteins and TNF-α and IL-6 expres-sions were decreased,expression of IL-10 was increased(P<0.05).circSKA3 could targeting regulate expression of miR-3163,and miR-3163 could targeting bind to ADAM9(P<0.05).Compared with sh-circSKA3 group,cell proliferation activity and scratch healing rate in sh-circSKA3+anti-miR-3163 and sh-circSKA3+pcDNA-ADAM9 groups were increased,number of invasive cells was in-creased,MMP-2,MMP-9 protein and TNF-α,IL-6 expressions were increased,while expression of IL-10 was decreased(P<0.05).Conclusion:Silencing circSKA3 expression can reduce expression of ADAM9 by up-regulating miR-3163 expression,inhibit ovarian cancer cell proliferation,migration and invasion,and regulate immune factor expression.

Objective:To observe the clinical efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)in the treatment of adult acute myeloid leukemia(AML)patients who are unfit for intensive chemotherapy.Methods:The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected,and the efficacy and safety were analyzed retrospectively.Results:After one course of treatment with VEN and AZA,16 out of 21 unfit AML patients reached complete remission(CR)/CR with incomplete hematologic recovery(CRi),2 patients reached partial remission(PR),the overall response rate(ORR)was 85.7％.Among the 16 patients with CR/CRi,13 achieved minimal residual disease(MRD)negativity.Among the 11 patients with adverse prognosis,8 achieved CR/CRi.By the deadline of follow-up,the median overall suivival(OS)of the entire cohort was not reached,with 1-year OS rate of 61.7％.The main adverse events of VEN combined with AZA were myelosuppression,gastrointestinal reactions and infections.There were 13 cases of leukopenia,7 cases of neutropenia,7 cases of anemia,4 cases of thrombocytopenia,and these hematologic adverse events were all grade 3-4.There were 11 cases with gastrointestinal reactions and 7 cases with infections.The above adverse events were controllable and tolerable.No tumor lysis syndrome or infection related death occurred.Conclusion:VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML,and it shows a good safety profile.

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

ObjectiveTo establish a UHPLC-MS/MS quantitative method for the determination of glucuronic acid， tartaric acid， glycolic acid， malic acid， lactic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid in cosmetics. MethodsSamples were prepared by ultrasonic extraction， cleansed by precipitating reagent and followed by high-speed centrifugation of the extraction solution. The supernatant was filtered by 0.22 μm Millipore filter. The continued filtrate was taken for analysis. A reversed phase column， Poroshell 120 EC-C₁₈ （2.7 μm， 4.6 mm×1 000 mm） was used with 0.1% formic acid buffer and acetonitrile as the mobile phase under the condition of gradient elution. The analytes were detected with electrospray ionization source in negative ion mode （ESI^-） and multiple reactions monitoring （MRM）， and quantified by external standard curve. ResultsThe method showed a good linearity of glucuronic acid， tartaric acid， malic acid， DL-2-hydroxybutyric acid sodium， benzilic acid， hydroxycaprylic acid and N-acetylneuraminic acid within the concentration range of 50.0‒2 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of glycolic acid， lactic acid， citric acid and mandelic acid within the concentration range of 100.0‒5 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of lactobionic acid and gluconic acid within the concentration range of 50.0‒5 000.0 μg·L^-1 （r>0.995）. The recoveries were in the range of 92.3%‒114.1%； the relative standard deviations （RSD） were in the range of 0.9%‒6.0% （n=3）. The detection limits of glucuronic acid， tartaric acid， malic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid were 0.003% while the detection limits of glycolic acid， lactic acid and mandelic acid were 0.006%. In 10 batches of commercially available cosmetics， eight batches showed positive result. ConclusionThe UHPLC-MS/MS method is efficient， sensitive and accurate and is applicable to the determination of 13 α-hydroxy acidic components in cosmetics.

Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.

Objective To investigate the effect of exosomal miR-146a-5p expression on gray matter volume in patients with major depressive disorder(MDD).Methods A total of 113 MDD patients(MDD group)and 107 healthy controls(HC)(HC group)were selected.Peripheral blood was collected and exosomes were isolated to quantify miR-146a-5p expression.Brain high-resolution T1 WI images of MDD and HC were obtained via MR,and gray matter volume was computed via SPM12 software.The interaction effect of"Depression×miR-146a-5p expression"on gray matter volume was analyzed using SPM's Flexible factorial design,and the between-group difference was assessed by extracting the mean value,thus to analyze whether MDD-related gray matter volume abnormalities were dependent on miR-146a-5p expression.Results Exosomal miR-146a-5p expression was significantly elevated in MDD group compared to HC group.Voxel-based factorial analysis revealed a relationship between high miR-146a-5p expression in MDD group and reduced gray matter volume in the anterior and posterior cingulate cortices(independent voxel threshold P＜0.001,AlphaSim corrected),and a significantly reduced gray matter volume as compared with HC group was detected in the two regions.Conclusion The exosomal miR-146a-5p is overexpressed in patients with MDD and may be associated with specific cortical atrophy in patients with MDD.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs