Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

OBJECTIVE To investigate the effect and mechanism of gracillin from Reineckia carnea on autophagy in non- small cell lung cancer A549 cells. METHODS Using A549 cells as subjects， the effects of different concentrations of gracillin （0.25， 0.5， 1， 2， 4 μmol/L） on the proliferation of cells were detected by CCK-8 after being treated for different time （12， 24， 48 h）. Compared with the control group without medication， the effect of gracillin （2 μmol/L） on the formation of autophagosomes in cells was observed by transmission electron microscope after 24 h of exposure. The aggregation of GFP-LC3 on autophagosome membrane was detected by GFP-LC3 plasmid transfection after being treated with gracillin （0.25， 0.5， 1， 2 μmol/L） for 24 h. Quantitative real-time PCR and Western blot assay were used to detect the mRNA and protein expressions of family with sequence similarity 102 member A（FAM102A）， the expressions of autophagy-related proteins [p62， Beclin-1， microtubule-associated protein 1 light chain 3B （LC3B）]， and the expressions of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway-related proteins in A549 cells after being treated with gracillin （0.25， 0.5， 1 and 2 μmol/L） for 24 h. RESULTS Gracillin significantly inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. The IC50 was 2.55 μmol/L at 24 h. After 24 h of gracillin treatment， autophagosomes with bilayer membrane structure were found in the cell cytoplasm， and GFP-LC3 green fluorescent spots on autophagosome membrane were obvious， representing an increasing trend as drug concentration. Compared with the control group， mRNA and protein expressions of FAM102A （0.5， 1， 2 μmol/L groups）， protein expression of Beclin-1 （1， 2 μmol/L groups） and LC3B-Ⅱ/LC3B-Ⅰ ratio （2 μmol/L group） were significantly increased in different concentrations of gracillin groups， while the protein expression of p62 （1， 2 μmol/L groups）， and the protein phosphorylations of Akt （1， 2 μmol/L groups） and PI3K （2 μmol/L group） were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gracillin can promote excessive autophagy in A549 cells by up-regulating mRNA and protein expressions of FAM102A and inhibiting PI3K/Akt signaling pathway， thus inhibiting cell proliferation.

Objective To investigate the effects of cinnamaldehyde,the main active component of cinnamon,on benzene-induced immune injury in mice and the related mechanism.Methods Forty male BALB/c mice were randomly divided into the control group,model group(benzene 500 mg/kg),cinnamaldehyde low,medium and high dose groups(5,25,50 mg/kg),with 8 mice in each group.Except the control group,mice in each group were treated with benzene by intragastric administration daily to induce immune and oxidative stress damage,but the intervention group was treated with cinnamaldehyde 5 times/week for 3 weeks.After medication,peripheral blood was collected 24 h after the last gavage for blood cell count,and the changes in body weight of mice in each group were observed.The pathological structure of the spleen and thymus was observed via hematoxylin-eosin(HE)staining.Peripheral blood mononuclear cells(PBMCs)of mice were extracted and the amounts of reactive oxygen species(ROS)and ATP in mitochondria were measured.Plasma levels of malondialdehyde(MDA)were measured using the barbituric acid method,the activity of glutathione peroxidase(GSH-PX)in plasmawith the dithiodinitrobenzoic acid methodand the activity of total superoxide dismutase(SOD)in plasma using the hydroxylamine method.Results After exposure to benzene,the body weight of the model group became lower(P<0.05).The spleen and thymus were damaged,and the indexes of the spleen and thymus were decreased(P<0.05).Counts of peripheral white blood cells and lymphocyteswere decreased(P<0.05).The activities of GSH and SOD in plasma were decreased(P<0.05),but the content of MDA was increased(P<0.05).The amount of mitochondrial ROS in PBMC was increased,while the ATP content was decreased(P<0.05).The weight of mice increased after treatment with cinnamaldehyde.The spleen and thymus tissues recovered well,and the indexes of the spleen and thymus were increased(P<0.05).Counts of peripheral white blood cells and lymphocytesin the high dose cinnamaldehyde group were increased(P<0.05).The activities of GSH and SOD in plasma were increased,while the content of MDA was decreased(P<0.05).The amount of mitochondrial ROS in PBMC was decreased,but the ATP content was increased(P<0.05).Treatment with cinnamaldehyde could alleviate the damage to the mitochondrial function of PBMC induced by benzene in mice,and 50 mg/kg was the best dose(P<0.05).The therapeutic effect of cinnamaldehyde had a dose-response relationship.Conclusion Cinnamaldehyde can inhibit benzene-induced immune injury and oxidative stress injury in mice by delivering an antioxidant effect and improving mitochondrial enhancement of PBMC.

Objective To study the application effect of quality control circle(QCC)in reducing the dissatisfaction rate of physical examination clients in health management center.Methods To establish QCC,selected the health check-up popula-tion in our hospital in September-2019 and March-2020,through the questionnaire investigation and analysis,compare the dis-satisfaction of the clients before and after the quality control circle.Results After carrying out QCC activities,the dissatisfaction of physical examination clients was significantly lower than that before QCC,and the difference was statistically significant(P＜0.05).Conclusion The activities of QCC in the health management center can effectively improve the quality of the physical examination work and reduce the dissatisfaction of the customers in the physical examination.It is of great significance to the health management.

Objective To construct a key nursing technology system for the treatment of patients exposed to nuclear radiation in hospitals,and provide technical guidance and support for emergency nursing rescue in hospitals of nuclear radiation accidents.Methods A research group was composed of a team with rich experience in nuclear radiation accidents.Based on 4 scenarios of nuclear radiation accidents(including external irradiation,internal irradiation,external contamination,internal contamination),the literature search was conducted to form the first draft of the system.Delphi method was used to complete 2 rounds of expert letter consultation,and the final draft of the key nursing technology system for hospital treatment of patients with nuclear radiation exposure was constructed according to the revised opinions of experts.Results A total of 16 experts completed 2 rounds of correspondence.The effective recovery rates were 100％and 80％;the recommendation rates were 65％and 50％;the authority coefficients(Cr)were 0.778 and 0.797;the coefficient of variation(CV)of the 2 rounds of expert letter consultation was ≤0.25.Finally,a key nursing technology system for in-hospital treatment of patients with nuclear radiation exposure was formed,including 5 first-level indicators,26 second-level indicators and 74 third-level indicators.Conclusion The constructed key nursing technology system for hospital treatment of patients with nuclear radiation exposure is highly practical and scientific,and it is conducive to the formation of standardized nuclear radiation exposure treatment procedures,and provides a theoretical basis for the training and evaluation of nursing staff related to nuclear radiation exposure.

Objective:To evaluate the correlation between ultrasound parameters of internal carotid artery blood flow and regional cerebral oxygen saturation (rScO 2) in elderly patients undergoing coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods:Sixty-four elderly patients undergoing elective CABG under CPB, aged 60-80 yr, regardless of gender, with body mass index of 18.1-28.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, with left ventricular ejection fraction≥50%, were selected. The rScO 2 and ultrasonic parameters of internal carotid artery including peak systolic velocity (PSV-ICA), end-diastolic velocity (EDV-ICA), diameter (D-ICA) and blood flow volume (Q-ICA) were recorded before anesthesia induction (T 0), at surgical skin incision (T 1), at 30 and 60 min of CPB (mean value was calculated, T 2), and at 30 and 60 min after termination of CPB (mean value was calculated, T 3). The ratio of unilateral internal carotid artery blood flow to cardiac output (Q/CO) was calculated. The receiver operating characteristic curve was used to analyze the accuracy of ultrasound parameters of internal carotid artery blood flow in predicting rScO 2 < 60%. Results:PSV-ICA was positively correlated with rScO 2 at T 0, T 1 and T 3 ( P<0.05), but no correlation was found between PSV-ICA and rScO 2 at T 2 ( P>0.05). There was no correlation between EDV-ICA and rScO 2 at each time point ( P>0.05). Q-ICA was positively correlated with rScO 2 at each time point ( P<0.05). Q/CO was not correlated with rScO 2 at T 1 ( P>0.05), but Q/CO was positively correlated with rScO 2 at T 2 and T 3 ( P<0.05). During the non-CPB period (T 0, T 1, T 3), the cutoff values of PSV-ICA and Q-ICA in predicting rScO 2< 60% were 51.35 cm/s and 283.5 ml/min respectively, the sensitivity was 0.900 and 0.900 respectively, and the specificity was 0.610 and 0.857 respectively (AUC=0.761, P=0.006; AUC=0.903, P< 0.001). During the CPB period, the cutoff values of Q-ICA and Q/CO in predicting rScO 2<60% were 296.5 ml/min and 5.84% respectively, the sensitivity was 0.900 and 0.800, and the specificity was 0.545 and 0.659 (AUC=0.764, P=0.001; AUC=0.748, P=0.002), respectively. Conclusions:PSV-ICA and Q-ICA are positively correlated with rScO 2 during the non-CPB period, and Q-ICA and Q/CO are positively correlated with rScO 2 during the CPB period in elderly patients undergoing CABG. PSV-ICA, Q-ICA and Q/CO can accurately predict rScO 2<60%.

Objective:To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance.Methods:The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1).Results:The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P＜0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33±0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P＜0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11,1.24±0.07, and 1.00±0.02, respectively (all P＜0.05). After radiotherapy, the expressions of γ-H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 ( P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 ( P=0.037), and after radiotherapy the expression of γ-H2AX increased. Conclusion:Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.

Objective:To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance.Methods:The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1).Results:The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P＜0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33±0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P＜0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11,1.24±0.07, and 1.00±0.02, respectively (all P＜0.05). After radiotherapy, the expressions of γ-H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 ( P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 ( P=0.037), and after radiotherapy the expression of γ-H2AX increased. Conclusion:Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.

Preliminary exploration of using ultrasound to quantitatively evaluate the development of epiphyseal cartilage and analyze its correlation with bone age, based on the ultrasound findings of the long bone joint end.