Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

ObjectiveTo analyze the long-term trends of the disease burden of diabetes attributed to metabolic factors in China from 1990 to 2019, and provide scientific recommendations for diabetes prevention and control in China. MethodsDescriptive analysis was conducted on the disease burden data of diabetes attributed to metabolic factors in China from 1990 to 2019, obtained from GBD 2019, encompassing death form diabetes, disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD). Joinpoint regression models were employed to analyze the long-term trends in mortality and DALY rates. Furthermore, the study examined the impact of two metabolic risk factors, high fasting plasma glucose (FPG) levels and high body mass index (BMI) levels, on the disease burden of diabetes. ResultsFrom 1990 to 2019, the overall standardized mortality and DALY rates attributed to metabolic factors for diabetes in the general population in China showed an upward trend, with both average annual percent changes (AAPCs) of 0.1% in the total population. The trend was upward in males with AAPCs of 0.9% and 0.6%, while it was downward in females with AAPCs of -0.4% and -0.3%. As age increased, the disease burden of diabetes attributed to metabolic factors showed an upward trend, with high FPG and high BMI ranking as the top two attributing risk factors. The disease burden of diabetes attributed to metabolic factors was higher in Chinese males than females. ConclusionThe disease burden of diabetes attributed to metabolic factors is increasing among the overall population and particularly among males, while the burden for female is declining. There is a need to increase intervention efforts for males aged 65 and above, provide scientific guidance on residents’ diet and lifestyle habits, and control blood glucose and body weight.

Background Job burnout is common among working populations. The current situation and influencing factors of job burnout have been studied in workers of many industries at home and abroad, except the express industry in China. Objective To understand the current situation of job burnout in express industry in a city of China, and to provide a scientific basis for developing measures to reduce the occurrence of job burnout. Methods In 2022, 432 express delivery workers in a city were selected by cluster random sampling, and their job burnout, anxiety symptoms, and depressive symptoms were evaluated by using the General Burnout Scale, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-9. Chi-square test was used to compare inter-group positive rates of job burnout. Spearman correlation analysis was used to analyze the correlation between selected variables. Positive job burnout, high level of exhaustion, and high level of cynicism were selected as dependent variables. Single-factor analysis was firstly carried out to identify statistically significant variables for subsequent logistic regression analysis. Results A total of 460 questionnaires were distributed and 432 valid questionnaires were recovered, with an effective recovery rate of 93.9%. There were 286 (66.2%) express delivery workers reporting job burnout. The positive rate of anxiety symptoms was 41.0%, and the positive rate of depressive symptoms was 34.0%. The job burnout score of the express industry workers [M (P₂₅, P₇₅)] was 1.8 (1.0, 2.5); the scores [M (P₂₅, P₇₅)] of exhaustion, cynicism, and professional efficacy were 1.0 (0.0, 2.6), 1.0 (0.0, 2.2), and 3.5 (1.2, 5.8), respectively; the score [M (P₂₅, P₇₅)] of anxiety symptoms was 1.5 (0.0, 7.0); the score [M (P₂₅, P₇₅)] of depressive symptoms was 1.0 (0.0, 8.0). There were statistical differences in the positive rates of job burnout among the express industry workers grouped by gender, education, monthly income, work shift system, overtime, anxiety symptoms, and depressive symptoms (P<0.05). The Spearman correlation analysis showed that there were significant positive correlations between the score of anxiety symptoms and the scores of job burnout, exhaustion, and cynicism (r_s=0.596, 0.689, 0.600, P<0.001); the score of depressive symptoms was also positively correlated with the scores of job burnout, exhaustion, and cynicism (r_s=0.601, 0.680, 0.607, P<0.001). The logistic regression analysis showed that women had a lower risk of job burnout than men (OR=0.458, 95%CI: 0.273, 0.768), and the risk of reporting positive job burnout was 3.140 times higher for those who worked overtime than those who did not (OR=3.140, 95%CI: 1.732, 5.693). Conclusion The current situation of job burnout in express industry is serious. Gender, education, monthly income, and overtime are the main influencing factors. Measures should be developed to reduce the occurrence of job burnout.

Background Job burnout is prevalent among the occupational population, which may lead to individual physical and mental discomfort and affect the quality of life and productivity of suffered workers. Most current chemical fiber factory workers are engaged in hazardous tasks with high frequency and high repetition, which are highly associated with anxiety and depressive symptoms, and subsequently lead to job burnout. Objective To understand the current situation and influencing factors of job burnout in workers of a chemical fiber factory in Xinxiang City of Henan Province, and to provide empirical evidence for preventing and reducing the occurrence of job burnout in target workers. Methods In 2022, the workers of a chemical fiber factory in Xinxiang City were selected by cluster random sampling. The Chinese versions of the Burnout Scale, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-9 were used to conduct a survey. SPSS 25.0 software was used for rank sum test, correlation analysis, and logistic regression analysis. Results A total of 1463 valid questionnaires were collected, with an effective recovery rate of 90.0%. The positive rate of mild and moderate job burnout in the chemical fiber factory employees was 39.4%, and the positive rate of serious job burnout was 14.3%. There were statistical differences in the positive rates of job burnout among the workers by gender, age, education level, position, work shift system, anxiety symptom severity, and depressive symptom severity (P<0.05). The results of Spearman correlation analysis showed that the score of anxiety symptoms was positively correlated with the total score of job burnout, as well as the dimensional scores of exhaustion and cynicism, and negatively correlated with the dimensional score of professional efficacy (r=0.671, 0.764, 0.673, −0.097; P<0.01). The score of depressive symptoms was also positively correlated with the total score of job burnout, as well as the dimensional scores of exhaustion and cynicism, and negatively correlated with the dimensional score of professional efficacy (r=0.688, 0.791, 0.723, −0.087; P<0.01). The results of logistic regression analysis showed that men had a higher risk of serious job burnout than women (OR=1.698, 95%CI: 1.163-2.479); workers aged ≤ 40 years old had a higher probability of serious job burnout than those aged 51 to 60 years old (OR=2.587, 95%CI: 1.310-5.109); non-assembly line production workers and assembly line production workers were more prone to serious job burnout than administrative management and logistics personnel (OR=6.511, 9.707, 95%CI: 1.539-27.548, 2.260-41.700); compared with other shift systems (three shifts and night shifts), the probability of serious job burnout was lower (OR=0.375, 95%CI: 0.254-0.553) in regular day shift workers; compared with frequent overtime work, those reporting no overtime work and occasional overtime work showed a lower risk of serious job burnout, with OR (95%CI) values of 0.114 (0.068-0.192) and 0.331 (0.194-0.564), respectively. Conclusion The positive rate of job burnout among the employees of the chemical fiber factory is high, and the anxiety symptoms and depressive symptoms are positively correlated with job burnout. Adjustment of work should be strengthened at multiple levels to improve anxiety symptoms and depressive symptoms of employees, and reduce the occurrence of job burnout.

Objective:To analyze the acupoint selection law of acupuncture for autism spectrum disorder (ASD) using data mining techniques.Methods:Literature related to acupuncture for ASD was retrieved from the CNKI, SinoMed, VIP, Wanfang, and PubMed databases from the establishment of the databases to April 1, 2022, and then a database of acupuncture prescriptions was established. The frequency analysis of acupoint use was performed using Microsoft Excel 2019; the Apriori algorithm was used to analyze the association law of acupoints/acupoint areas; SPSS 26.0 was used to perform intergroup cluster analysis.Results:A total of 97 relevant articles with 97 acupuncture prescriptions and 98 acupoints/acupoint areas were included. The most frequently used acupoint was Shenmen (HT 7). The acupoint area of Jin's three-needle therapy and the Governor Vessel acupoints are commonly used. The most frequently occurring part of the acupoint/acupoint area was the head, and the most commonly used specific acupoint was the rendezvous acupoint. Association rule analysis yielded 40 groups of acupoints/acupoint areas, and the most commonly used combination was Laogong (PC 8) and Shenmen (HT 7). Four categories were extracted among high-frequency acupoints/acupoint areas by cluster analysis.Conclusion:Acupuncture treatment for ASD mainly selects the head acupoints, mainly selecting the acupoint area of Jin's three-needle therapy and the Governor Vessel acupoints, and paying attention to the use of specific acupoints.

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Depressive Disorder, Major/metabolism* ; Basal Forebrain ; Depression ; Hippocampus/metabolism* ; Cholinergic Agents

Objective: To investigate the effect of acetyl-CoA carboxylase 1 (ACC1) knockdown on the migration of esophageal squamous cell carcinoma (ESCC) KYSE-450 cell and underlying mechanism. Methods: Lentiviral transfection was conducted to establish sh-NC control cell and ACC1 knocking down cell (sh-ACC1). Human siRNA HSP27 and control were transfected by Lipo2000 to get si-HSP27 and si-NC. The selective acetyltransferase P300/CBP inhibitor C646 was used to inhibit histone acetylation and DMSO was used as vehicle control. Transwell assay was performed to detect cell migration. The expression of HSP27 mRNA was examined by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and the expressions of ACC1, H3K9ac, HSP27 and epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin were detected by western blot. Results: The expression level of ACC1 in sh-NC group was higher than that in sh-ACC1 group (P<0.01). The number of cell migration in sh-NC group was (159.00±24.38), lower than (361.80±26.81) in sh-ACC1 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC group were statistically significant compared with sh-AAC1 group (P<0.05). The migrated cell number in sh-NC+ si-NC group was (189.20±16.02), lower than (371.60±38.40) in sh-ACC1+ si-NC group (P<0.01). The migrated cell number in sh-NC+ si-NC group was higher than that in sh-NC+ si-HSP27 group (152.40±24.30, P<0.01), and the migrated cell number in sh-ACC1+ si-NC group was higher than that in sh-ACC1+ si-HSP27 group (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-NC+ si-NC group were significantly different from those in sh-ACC1+ si-NC and sh-NC+ si-HSP27 groups (P<0.01). The protein expression levels of E-cadherin and Vimentin in sh-ACC1+ si-NC group were significantly different from those in sh-ACC1+ si-HSP27 group (P<0.01). After 24 h treatment with C646 at 20 μmmo/L, the migrated cell number in sh-NC+ DMSO group was (190.80±11.95), lower than (395.80±17.10) in sh-ACC1+ DMSO group (P<0.01). The migrated cell number in sh-NC+ DMSO group was lower than that in sh-NC+ C646 group (256.20±23.32, P<0.01). The migrated cell number in sh-ACC1+ DMSO group was higher than that in sh-ACC1+ C646 group (87.80±11.23, P<0.01). The protein expressions of H3K9ac, HSP27, E-cadherin and Vimentin in sh-NC+ DMSO group were significantly different from those in sh-ACC1+ DMSO group and sh-NC+ C646 group (P<0.01). The protein expression levels of H3K9ac, HSP27, E-cadherin and Vimentin in sh-ACC1+ DMSO group were significantly different from those in sh-ACC1+ C646 group (P<0.01). Conclusion: Knockdown of ACC1 promotes the migration of KYSE-450 cell by up-regulating HSP27 and increasing histone acetylation.
Humans ; Esophageal Neoplasms/pathology* ; Esophageal Squamous Cell Carcinoma/genetics* ; Vimentin/metabolism* ; Dimethyl Sulfoxide ; HSP27 Heat-Shock Proteins/metabolism* ; Histones/metabolism* ; Cadherins/metabolism* ; Cell Movement ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Epithelial-Mesenchymal Transition/genetics* ; Gene Expression Regulation, Neoplastic