OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Objective:To analyze clinical features, short-term efficacy and side effects of salvage re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy, to investigate the prognostic factors of re-irradiation with precise radiotherapy techniques.Methods:A retrospective analysis was performed on patients with locally recurrent esophageal squamous cell carcinoma after definitive chemoradiotherapy treated in the Fourth Hospital of Hebei Medical University from January 2008 to December 2016. The patients underwent re-irradiation therapy (re-RT) or re-irradiation therapy concurrent chemotherapy (re-CCRT). The main observation index was after-recurrence survival (ARS), which was calculated by Kaplan-Meier method for survival analysis. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox regression model.Results:A total of 109 patients were included, with a median age of 66 years (43-89 years), and a median follow-up time of 120.8 months (79.0-176.5 months). The objective response rates (ORR) and dysphagia improvement rates (DIR) in all patients were 64.2% and 63.0%, respectively. The median ARS and 1-, 3-, 5-, 8-year survival rates in all patients were 7.8 months and 32.1%, 9.2%, 7.3% and 2.3%, respectively. The median ARS and 1-, 3-, 5-years survival rates were 10.8 months and 45.9%, 13.5%, 10.8% for patients with time to recurrence (TTR) ≥24 months, significantly longer than those of 5.7 months and 25.0%, 6.9%, 5.6% for patients with TTR<24 months ( χ2=7.99, P=0.005). The median ARS in groups with re-irradiation dose of ≤50 Gy,>50-54 Gy, and>54 Gy groups were 5.7, 10.0 and 8.1 months, respectively ( χ2=6.94, P=0.031). The 1-, 3- and 5-year survival rates were 30.4%, 5.1%, and 3.8% for re-RT versus 36.7%, 20.0%, and 16.7% for re-CCRT ( χ2=2.12, P=0.145). Multivariate analysis showed that TTR ( HR=0.607, 95% CI=0.372-0.991, P=0.046) and lesion length ( HR=0.603, 95% CI=0.371-0.982, P=0.042) were the independent factors for ARS. There was no significant difference in ≥2 grade pneumonitis and 2-3 grade radiation esophagitis between the re-RT and re-CCRT groups ( χ2=0.25, P=0.619; χ2=0.51, P=0.808). The morbidity of ≥2 grade myelosuppression in the re-RT group was significantly lower than that in the re-CCRT group (3.7% vs. 36.7%, χ2=18.15, P<0.001). Conclusions:Precise re-irradiation therapy for patients with locally recurrent esophageal cancer after definitive chemoradiotherapy can alleviate dysphagia, but ARS remains poor. Re-irradiation dose range from>50-54 Gy may be suitable for locally relapse patients as salvage treatment. Patients with TTR≥24 months and lesion length ≤5 cm obtain favorable prognosis.

Objective:To investigate the current situation and correlation of perceived social support,achievement motivation,and depression among nursing graduates of a medical college in Anhui Province.Methods:A convenient sampling method was used to select 286 graduates from the School of Nursing in a medical college in Anhui Province as the research subjects.They were investigated using a general information questionnaire,the Perceived Social Support Scale,the Achievement Motivation Scale,and the Self-Rating Depression Scale.SPSS 23.0 and SPSS process plug-in were used to conduct correlation analysis and mediation effect test.Results:Perceived social support and achievement motivation were negatively correlated with depression(r=-0.413,-0.306,P＜0.01).Perceived social support was positively correlated with achievement motivation(r=0.323,P＜0.01).Achievement motivation partially mediated the relationship between perceived social support and depression,with a mediating effect of 14.99%of the total effect.Conclusion:The perceived social support among nursing graduates can have a direct impact on depression,and can also predict depression through the indirect effect of achievement motivation.

Objective:To explore changes in high-risk sexual behaviors and associated factors in HIV-infected men who have sex with men (MSM) in industrial workers, and provide evidence for designing behavioral interventions for this population.Methods:In this observational study, HIV-infected MSM were recruited in industrial workers using convenient sampling during August to September 2021. The sample size was estimated to be 530. A questionnaire was used and combined with routine follow-up to collect socio-demographic characteristics, high-risk sexual behaviors, partner notification, viral load testing and history of sexually transmitted diseases before and after diagnosis of HIV infection. The χ2 test was used to analyze the changes in high-risk sexual behaviors before and after diagnosis and logistic regression was conducted to identify factors associated with high-risk sexual behaviors. Results:A total of 560 HIV-infected MSM in industrial workers were recruited in this study. Of whom, 32.1% (180/560) had unprotected anal intercourse (UAI) within 12 months after diagnosis . The proportions of those having UAI with casual, commercial and regular same-sex partners significantly decreased from 73.4% (381/519), 75.1% (187/249) and 69.5% (207/298) within 12 months before diagnosis to 36.2% (146/403), 40.2% (86/214) and 34.2% (67/196) within 12 months after diagnosis , respectively. Educational level of college or above (a OR=0.41, 95% CI:0.23-0.71), passive anal sex (a OR=0.40, 95% CI:0.19-0.85), both active and passive anal sex after diagnosis (a OR=0.40, 95% CI:0.20-0.83) and no unprotected oral sex (a OR=0.02, 95% CI:0.01-0.05) were negatively associated with UAI within 12 months after diagnosis. Whereas, not considering necessary to use condom consistently after having repeated undetectable viral load (a OR=3.02, 95% CI:1.37-6.69) was positively associated with UAI within 12 months after diagnosis. Conclusions:Compared with that before diagnosis of HIV infection, although the prevalence of UAI seemed to decrease in HIV-infected MSM in industrial workers after diagnosis, nearly one third of them had high-risk sexual behaviors. Therefore, relevant interventions should be strengthened to reduce high-risk sexual behaviors.

Objective    To reveal the risk factors for delayed recovery and complications in infants with weight≤ 5.0 kg after surgical ventricular septal defect (VSD) closure. Methods    We retrospectively reviewed a consecutive series of 86 patients with weight≤5.0 kg who were admitted to our institution for surgical VSD closure between January 2016 and July 2019, including 31 males and 55 females with an age of 17-266 (80.3±40.4) d and a weight of 2.5-5.0 (4.4±0.6) kg. The VSDs were divided into perimembranous (n=65, 75.6%), subaortic (n=17, 19.8%) and subaortic combined muscular types (n=4, 4.7%). Mechanical ventilation (MV) time≥24 h or ICU stay≥72 h were defined as delayed recovery. Death, sudden circulatory arrest, complete heart block requiring a permanent or temporary pacemaker implantation, neurological complications, reoperation (for residue shunt or valvular regurgitation), reintubation and diaphragmatic paralysis were considered as significant major adverse events. Results    There was no death, reoperation due to residual VSD or neurological complication. Totally 51 (59.3%) patients had MV timec≥24 h and 51 (59.3%) patients stayed in the ICU≥ 72 h. Two (2.3%) patients required temporary pacemaker and six (7.0%) patients required reintubation. During the follow-up of 3-36 (15.8±8.8) months, 1 patient died of pneumonia after discharge, 5 patients suffered mild tricuspid valve regurgitation and 1 patient suffered decreased left ventricular systolic function in the follow-up. No aortic valve injuries occurred. Conclusion    For patients whose weight≤5.0 kg, short-term results of surgical VSD closure are excellent. Low weight and age may prolong MV time; low birth weight and pulmonary hypertension may prolong ICU stay, but are not independent risk factors.

Objective    To analyze the clinical efficacy of transthoracic occlusion via a right subaxillary incision and conventional surgery in the treatment of ventricular septal defect (VSD). Methods    The clinical data of patients with congenital VSD undergoing right subaxillary incision surgery in our hospital from January 2017 to January 2020 were retrospectively analyzed. According to the surgical methods, the patients were divided into two groups: a conventional surgery group (conventional group) and a transthoracic occlusion group (occlusion group). There were 221 patients in the conventional group, including 97 males and 124 females, with an average age of 2.6±2.2 years and an average weight of 13.4±6.2 kg; there were 185 patients in the occlusion group, including 90 males and 95 females, with an average age of 3.2±2.6 years and an average weight of 14.7±6.6 kg. The clinical effectiveness was compared. Results    The success rate of surgery was 100% in both groups. The intraoperative blood loss was less in the occlusion group (P<0.05). The incision length, operation time, postoperative mechanical ventilation time, retention time in the intensive care unit, the time to resume normal diet and normal activities after operation were all shorter than those in the conventional group (P all <0.05). The total cost during hospitalization of the conventional group was less than that of the occlusion group (P<0.001). There was no statistical difference in the incidence rate of perioperative complications between the two groups (P>0.05). During the follow-up (15.8±8.8 months), the incidence of complications in the conventional group was higher than that in  the occlusion group with a statistical difference (P<0.001). Conclusion    Compared with conventional surgery, transthoracic occlusion for VSD via right subaxillary incision has the advantages of smaller incision, shorter operation time, less blood loss, shorter postoperative recovery time and less long-term complications. However, the total hospitalization cost is relatively high, mainly because of the high consumables cost, and the long-term effects still need further comparative observation.