ObjectiveDirect continuous monitoring of arterial blood pressure is invasive and continuous monitoring cannot be achieved by traditional cuffed indirect blood pressure measurement methods. Previously, continuous non-invasive arterial blood pressure monitoring was achieved by using photoplethysmography (PPG), but it is discrete values of systolic and diastolic blood pressures rather than continuous values constructing arterial blood pressure waves. This study aimed to reconstruct arterial blood pressure wave signal based on CNN-LSTM using PPG to achieve continuous non-invasive arterial blood pressure monitoring. MethodsA CNN-LSTM hybrid neural network model was constructed, and the PPG and arterial blood pressure wave synchronized recorded signal data from the Medical Information Mart for Intensive Care (MIMIC) were used. The PPG signals were input to this model after noise reduction, normalization, and sliding window segmentation. The corresponding arterial blood pressure waves were reconstructed from PPG by using the CNN-LSTM hybrid model. ResultsWhen using the CNN-LSTM neural network with a window length of 312, the error between the reconstructed arterial blood pressure values and the actual arterial blood pressure values was minimal: the values of mean absolute error (MAE) and root mean square error (RMSE) were 2.79 mmHg and 4.24 mmHg, respectively, and the cosine similarity is the optimal. The reconstructed arterial blood pressure values were highly correlated with the actual arterial blood pressure values, which met the Association for the Advancement of Medical Instrumentation (AAMI) standards. ConclusionCNN-LSTM hybrid neural network can reconstruct arterial blood pressure wave signal using PPG to achieve continuous non-invasive arterial blood pressure monitoring.

Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway.

OBJECTIVE: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker. METHODS: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL). RESULTS: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m ³. The OELs for COEs exposure using the BBMD were 0.00170 mg/m ³ for the total population, 0.00158 mg/m ³ for males, and 0.00174 mg/m ³ for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m ³, respectively. CONCLUSION Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m ³. This value will provide a benchmark for determining possible OELs.
Male ; Female ; Animals ; Coke ; Polycyclic Aromatic Hydrocarbons ; DNA Copy Number Variations ; Benchmarking ; Occupational Exposure/analysis* ; DNA, Mitochondrial/genetics* ; DNA Damage

OBJECTIVES: To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS. METHODS: The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively). The control group was selected from jaundice neonates who were observed in the neonatal department of the hospital during the same period, and they had no pathological factors causing neonatal jaundice. Peripheral blood samples were collected on day 1, day 3, and day 7 after admission for the ARDS group, and on the day of admission for the control group. Serum cf-DNA levels were measured using a fluorescence enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using enzyme-linked immunosorbent assay. A Pearson correlation analysis was used to evaluate the correlation of serum cf-DNA levels with serum IL-6 and TNF-α levels. RESULTS: A total of 50 neonates were enrolled in the ARDS group, including 15 neonates with mild ARDS, 25 with moderate ARDS, and 10 with severe ARDS. Twenty-five neonates were enrolled in the control group. Compared with the control group, the serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased (P<0.05). Compared with the mild ARDS group, the serum levels of cf-DNA, IL-6, and TNF-α in the moderate and severe ARDS groups were significantly increased (P<0.05), and the increase was more significant in the severe ARDS group (P<0.05). The serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased on day 3 after admission and significantly decreased on day 7 after admission compared with those on day 1 after admission (P<0.05). The Pearson correlation analysis showed that there was a positive correlation between serum cf-DNA levels and IL-6 levels as well as TNF-α levels in 50 neonates with ARDS (P<0.05). CONCLUSIONS There is an excessive expression of NETs in neonates with ARDS, and dynamic monitoring of serum cf-DNA levels has certain clinical value in evaluating the severity and early diagnosis of ARDS in neonates.
Infant, Newborn ; Humans ; Extracellular Traps ; Prospective Studies ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Prognosis ; ROC Curve ; Respiratory Distress Syndrome ; DNA

【Subjects】 To investigate the clinical application value of myocardial contrast echocardiography （MCE） in selecting CTO-PCI patients. MethodsFrom February 2019 to March 2020， a total of 50 patients with chronic coronary artery occlusion were consecutively selected as the research subjects. MCE and two-dimensional speck-tracking echocardiography were completed before and 12 months after interventional therapy. The primary end point was major adverse cardiovascular events. Patients were divided into groups according to the preoperative myocardial perfusion level of MCE. The improvement of left ventricular function was evaluated by two-dimensional echocardiography and left ventricular global longitudinal strain. ResultsCompared with the abnormal perfusion group， the improvement of GLS in the normal perfusion group was greater （P=0.028）. The wall motion score index （WMSI） of the abnormal perfusion group before PCI was higher than that of the normal perfusion group （P=0.002）. WMSI in the abnormal perfusion group was higher than that in the normal perfusion group one year after PCI （P<0.001）. The left ventricular GLS（P=0.008）.WMSI（P=0.016） and left ventricular end-diastolic volume（P=0.032） in the normal perfusion group were improved compared with those before operation； The postoperative perfusion score of patients with abnormal perfusion was significantly improved （ P=0.032）. ConclusionMCE has clinical application value in optimizing the selection of CTO-PCI patients. CTO patients with different myocardial perfusion types have different benefits after PCI.

Objective To design and validate a novel surgical guide for retrieval of foreign body in jaw. Methods Firstly, a surgical guide based on cone beam computed tomography and trephine technique was designed to remove broken dental instrument fragments. Its feasibility and accuracy were assessed by removing broken dental instrument in goat mandible, and then it was successfully applied in clinical cases. The linear and angular discrepancies between actual and planned columnar bone with imaginary fragment was analyzed. The euclidean distance was measured at the hex and apex of the columnar bone and the angle of axis deviation was also calculated. We obtained seven parameters (cdh, cda, hdh, hda, vdh, vda, and ad) to describe deviations. Results Mean central deviation at the hex and apex was (0.51 ± 0.14) mm and (0.62 ± 0.19) mm, respectively. Accompanying mean values were as follow: horizontal deviation at the hex was (0.48 ± 0.16) mm, horizontal deviation at the apex was (0.52 ± 0.22) mm, vertical deviation at the hex was (0.17 ± 0.09) mm, vertical deviation at the apex was (0.29 ± 0.13) mm, and angular deviation of (5.38 ± 3.43) degrees. In a clinical case, the guide successfully located and removed the fracture file. Conclusion This study reveals that this kind novel surgical guide could aid to locate and remove the foreign body in jaw.

OBJECTIVE: To investigate the therapeutic effect of Yixin Ningshen Tablet (YXNS) on comorbidity of myocardial infarction (MI) and depression in rats and explore the underlying mechanism. METHODS: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights, including control, model, fluoxetine (FLXT, 10 mg/kg), low-dose YXNS (LYXNS, 100 mg/kg), and high-dose YXNS (HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction (MI) area and myocardial apoptosis was also detected. Serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), adrenocorticotrophic hormone (ACTH), corticosterone (CORT), and norepinephrine (NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5'-monophosphate -activated protein kinase (AMPK), p-AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase (IDO1), kynurenine 3-monooxygenase (KMO), and kynureninase (KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. RESULTS: Compared with the model group, the cardiac function of rats treated with YXNS improved significantly (P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats (P<0.01 or P<0.05), promoted AMPK phosphorylation, and increased PGC-1α protein expression (P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH, and CORT (all P<0.05). Moreover, HYXNS decreased the mRNA expressions of IDO1, KMO and KYNU (P<0.05). CONCLUSIONS YXNS can relieve MI by enhancing myocardial energy metabolism. Meanwhile, YXNS can alleviate depression by resisting inflammation and increasing availability of monoamine neurotransmitters. It may be used as a potential drug to treat comorbidity of MI and depression.
AMP-Activated Protein Kinases/metabolism* ; Adrenocorticotropic Hormone ; Animals ; Comorbidity ; Depression/drug therapy* ; Energy Metabolism ; Interleukin-6/metabolism* ; Myocardial Infarction/pathology* ; Neurotransmitter Agents ; Rats ; Rats, Sprague-Dawley ; Serotonin/metabolism* ; Tablets ; Tumor Necrosis Factor-alpha/metabolism*

Objective To investigate the expression and correlation of Runt-related transcription factor 3(RUNX3)and enhancer of zeste homolog 2(EZH2)in rectal cancer,and to reveal the relationship between the expression of RUNX3 and EZH2 and the sensitivity of XELOX regimen to neoadjuvant chemotherapy in locally advanced rectal cancer patients. Methods The carcinoma and paracancerous tissues of 31 patients with rectal adenocarcinoma and no preoperative antitumor therapy were selected as cancer group and paracancer group,respectively.The relative mRNA levels of RUNX3 and EZH2 in the two groups were measured by real-time quantitative reverse transcription-polymerase chain reaction,and the protein levels were determined by immunohistochemical assay.The expression of RUNX3 and EZH2 was compared between cancer tissue and paracancerous tissue.The pre-treatment wax blocks of 26 patients with locally advanced rectal cancer who received 3 cycles of XELOX regimen as neoadjuvant chemotherapy before surgery were selected as the pre-neoadjuvant therapy group,and the postoperative pathological wax blocks were selected as the post-neoadjuvant treatment group.Tumor regression grade(TRG)was determined to evaluate the efficacy of neoadjuvant therapy.Immunohistochemical assay was used to detect the protein levels of RUNX3 and EZH2 in the two groups,and then the relationship between the expression patterns of the two proteins and the efficacy of neoadjuvant chemotherapy was analyzed. Results Compared with paracancerous tissue,the cancer tissue showed down-regulated mRNA level and reduced positive protein expression rate of RUNX3,while up-regulated mRNA level(
Core Binding Factor Alpha 3 Subunit/genetics* ; Enhancer of Zeste Homolog 2 Protein/genetics* ; Humans ; Neoadjuvant Therapy ; Rectal Neoplasms/drug therapy* ; Transcription Factor 3

OBJECTIVE: To investigate the effects of nuclear transcription factor-κB(NF-κB)/amide adenine dinucleotide phosphate oxidase 1(NOX1) signaling pathway in tumor necrosis factor-α(TNF-α) induced apoptosis of A549 cells. METHODS: i) A549 cells were stimulated with TNF-α at the concentrations of 0.00, 0.25, 0.50, and 1.00 nmol/L. CCK-8 assay was used to detect the cell viability to screen the optimal stimulating concentration of TNF-α. ii) A549 cells at logarithmic growth stage were randomly divided into four groups, the control group, the TNF-α group, the BAY11-7082(NF-κB inhibitor) group and the TNF-α+BAY11-7082 group. The cells in the control group were not treated. The TNF-α and BAY11-7082 groups were stimulated with 0.50 nmol/L TNF-α and 5 μmol/L BAY11-7082, respectively. The TNF-α+BAY11-7082 group was stimulated by both TNF-α and BAY11-7082. After 24 hours of culture, the cell survival rate was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptotic rate, and Western blotting was used to detect the relative expression of NF-κB(p65) and NOX1 proteins. RESULTS: i) When A549 cells were stimulated with TNF-α at the concentration of 0.50 nmol/L, the cell proliferative activity was reduced and the cell apoptosis was promoted. This concentration was selected as the stimulation dose of TNF-α in subsequent experiments. ii) The survival rate of A549 cells in the TNF-α group decreased(P<0.05), the apoptotic rate and the protein expressions of NF-κB(p65) and NOX1 increased in TNF-α group(all P<0.05) compared with the control group. In BAY11-7082 group, the survival rate and the relative expression of NF-κB(p65) and NOX1 of A549 cells were decreased(all P<0.05), and the apoptotic rate of A549 cells was increased(P<0.05) compared with the control group. A549 cells in TNF-α+BAY11-7082 group changed from a long spindle shape to an irregular one. The cell survival rate increased(P<0.05), the apoptotic rate and the relative expression of NF-κB(p65) and NOX1 decreased(all P<0.05) compared with the TNF-α group. CONCLUSION: NF-κB/NOX1 signaling pathway is involved in A549 cells apoptosis induced by TNF-α.

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.