Exploring Epigenetic and Genetic Modulation in Animal Responses to Thermal Stress.

There is increasing evidence indicating that global temperatures are rising significantly, a phenomenon commonly referred to as 'global warming', which in turn is believed to be causing drastic changes to the global climate. Global warming (GW) directly impacts animal health, reproduction, production, and welfare, presenting several challenges to livestock enterprises. Thermal stress (TS) is one of the key consequences of GW, and all animal species, including livestock, have diverse physiological, epigenetic and genetic mechanisms to respond to TS. As a result, TS can significantly affect an animals' health, immune responsiveness, metabolic pathways etc. which can also influence the productivity, performance, and welfare of animals. Moreover, prolonged exposure to TS can lead to transgenerational and intergenerational changes that are mediated by epigenetic changes. For example, in several animal species, the effects of TS are encoded epigenetically during the animals' growth or productive stage, and these epigenetic changes can be transmitted intergenerationally. Such epigenetic changes can affect animal productivity by changing the phenotype so that it aligns with its ancestors' environment, irrespective of its immediate environment. Furthermore, epigenetic and genetic changes can also help protect cells from the adverse effects of TS by modulating the transcriptional status of heat-responsive genes in animals. This review focuses on the genetic and epigenetic modulation and regulation that occurs in TS conditions via HSPs, histone alterations and DNA methylation.

Asperuloside Promotes Apoptosis of Cervical Cancer Cells through Endoplasmic Reticulum Stress-Mitochondrial Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of asperuloside on cervical cancer based on endoplasmic reticulum (ER) stress and mitochondrial pathway.@*METHODS@#Different doses (12.5-800 µg/mL) of asperuloside were used to treat cervical cancer cell lines Hela and CaSki to calculate the half maximal inhibitory concentration (IC50) of asperuloside. The cell proliferation was analyzed by clone formation assay. Cell apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were determined by flow cytometry. The protein expressions of cleaved-caspase-3, Bcl-2, Bax, Cyt-c, cleaved-caspase-4 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot. And the inhibitor of ER stress, 4-phenyl butyric acid (4-PBA) was used to treat cervical cancer cells to further verify the role of ER stress in the apoptosis of cervical cancer cells induced by asperuloside.@*RESULTS@#Asperuloside of 325, 650, and 1300 µg/mL significantly inhibited the proliferation and promoted apoptosis of Hela and CaSki cells (P<0.01). All doses of asperuloside significantly increased intracellular ROS levels, reduced mitochondrial membrane potential, significantly reduced Bcl-2 protein expression level, and increased Bax, Cyt-c, GRP78 and cleaved-caspase-4 expressions (P<0.01). In addition, 10 mmol/L 4-PBA treatment significantly promoted cell proliferation and reduced apoptosis (P<0.05), and 650 µg/mL asperuloside could reverse 4-PBA-induced increased cell proliferation, decreased apoptosis and cleaved-caspase-3, -4 and GRP78 protein expressions (P<0.05).@*CONCLUSION@#Our study revealed the role of asperuloside in cervical cancer, suggesting that asperuloside promotes apoptosis of cervical cancer cells through ER stress-mitochondrial pathway.

Interaction of C/EBPß with SMAD2 and SMAD4 genes induces the formation of lipid droplets in bovine myoblasts.

As a key component of Transforming growth factor-ß (TGF-ß) pathway, Smad2 has many crucial roles in a variety of cellular processes, but it cannot bind DNA without complex formation with Smad4. In the present study, the molecular mechanism in the progress of myogenesis underlying transcriptional regulation of SMAD2 and SMAD4 had been clarified. The result showed the inhibition between SMAD2 and SMAD4, which promotes and inhibits bovine myoblast differentiation, respectively. Further, the characterization of promoter region of SMAD2 and SMAD4 was analyzed, and identified C/EBPß directly bound to the core region of both SMAD2 and SMAD4 genes promoter and stimulated the transcriptional activity. However, C/EBPß has lower expression in myoblasts which plays vital function in the transcriptional networks controlling adipogenesis, while the overexpression of C/EBPß gene in myoblasts significantly increased SMAD2 and SMAD4 gene expression, induced the formation of lipid droplet in bovine myoblasts, and promoted the expression of adipogenesis-specific genes. Collectively, our results showed that C/EBPß may play an important role in the trans-differentiation and dynamic equilibrium of myoblasts into adipocyte cells via promoting an increase in SMAD2 and SMAD4 gene levels. These results will provide an important basis for further understanding of the TGFß pathway and C/EBPß gene during myogenic differentiation.

Effects of pressure controlled ventilation-volume guaranteed mode on intraoperative pulmonary ventilation and postoperative pulmonary complications in elderly patients undergoing thoracoscopic lobectomy / 肿瘤研究与临床

Objective:To explore the effects of pressure controlled ventilation-volume guaranteed (PCV-VG) mode on intraoperative pulmonary ventilation and postoperative pulmonary complications (PPC) in elderly patients undergoing thoracoscopic lobectomy.Methods:Sixty patients of American Society of Anesthesiologists (ASA) classification Ⅱor Ⅲ, aged 65-80 years old, with body mass index (BMI) 18-30 kg/m 2, received thoracoscopic lobectomy under general anesthesia from November 2021 to June 2022 in the Second Hospital of Shanxi Medical University were recruited. The patients were divided into PCV-VG and volume-controlled ventilation (VCV) groups using the randomized number table method, with 30 patients in each group. The ventilatory parameters of two-lung ventilation were set to respiratory rate (RR) at 10-12 breaths/min, with a tidal volume (VT) of 8 ml/kg (ideal body weight). The ventilatory parameters of one-lung ventilation (OLV) were set at 12-16 breaths/min, with a VT of 6 ml/kg (IBW). The peak airway pressure (Ppeak), plateau airway pressure (Pplat), driving pressure (ΔP), dynamic lung compliance (Cdyn), end-tidal carbon dioxide (ETCO 2), heart rate (HR), mean arterial pressure (MAP), partial pressure of oxygen (PaO 2) and partial pressure of carbon dioxide (PaCO 2) were obtained at 1 min before OLV (T 0), 30 min after OLV (T 1) and 60 min after OLV (T 2). The incidence and severity of PPC, chest tube duration time and postoperative hospital stay time were recorded. Results:The Ppeak, Pplat and ΔP were higher and Cdyn was lower in both groups at T 1-T 2 than at T 0 (all P<0.001). The Ppeak, Pplat and ΔP were higher and Cdyn was lower in PCV-VG group than in VCV group (all P<0.05). There were no statistical differences in HR, MAP, ETCO 2, PaO 2 and PaCO 2 between the two groups (all P > 0.05). There were no statistical differences in the incidence of PPC [43.3% (13/30) vs. 30.0% (9/30)] and chest tube duration time [(4.4±0.9) d vs. (4.2±1.2) d] between VCV group and PCV-VG group (all P>0.05). Compared with VCV group, the proportion of patients with ≥grade 2 PPC was lower in PCV-VG group [10.0% (3/30) vs. 36.7% (11/30), χ2=5.96, P<0.05]. The postoperative hospital stay time in PCV-VG group was shorter than that in VCV group [(6.4±1.3) d vs. (8.0±1.9) d, t = 4.85, P<0.05]. Conclusions:PCV-VG mode can effectively reduce the severity of PPC, shorten the postoperative hospital stay time and improve the prognosis in elderly patients undergoing thoracoscopic lobectomy.

NR4A1 suppresses cisplatin-induced ferroptosis in renal proximal tubular epithelial cells by up-regulating the expression of NRF2 / 中华肾脏病杂志

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Effect of pre-injection of young rat plasma on cognitive dysfunction after cerebral ischemia-reperfusion in aged rats and the role of PI3K/Akt signaling pathway / 中华麻醉学杂志

Objective:To evaluate the effect of pre-injection of young rat plasma on cognitive dysfunction after cerebral ischemia-reperfusion (I/R) in aged rats and the role of phosphatidylinositol 3-kinase/serine threonine protein kinase (PI3K/Akt) signaling pathway.Methods:Seventy-two SPF-grade healthy male Sprague-Dawley rats, aged 18 months, weighing 600-650 g, were divided into 4 groups ( n=18 each) by the random number table method: control group (group C), cerebral I/R group (group IR), pre-injection of young rat plasma group (group P) and PI3K inhibitor LY294002 group (group LY). In group P and group LY, young rat plasma 100 μl/time was injected via the tail vein. In group C and group IR, the equal volume of normal saline was injected via the the tail vein, 2 times a week for 4 weeks. Then the model of cerebral I/R injury was developed under sevoflurane anesthesia in IR, P and LY groups. LY294002 0.3 mg/kg was injected through the tail vein at 1 h before anesthesia in LY group. The neurological deficit score (Longa score) was performed at 24 h after reperfusion, and then 6 rats were randomly sacrificed, and brain tissues were obtained to determine the cerebral infarct volume. Spontaneous mobility and anxiety-like behavior were assessed by the open field test at day 29 of reperfusion, and cognitive function was assessed by the novel object recognition test at day 30 of reperfusion. At the end of the behavioral test, rats were sacrificed, hippocampal tissues were isolated for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), postsynaptic dense protein-95 (PSD-95) and synaptic vesicle protein (SYN) (by Western blot), and the dendritic length and dendritic spine density of neurons in the hippocampal CA1 region. Results:There was no significant difference in motor speed, distance traveled, and time of staying at the center of the open field among the four groups ( P>0.05). Compared with group C, the Longa score and cerebral infarct volume were significantly increased, the percentage of novel object exploration and discrimination index were decreased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in IR, P and LY groups ( P<0.05). Compared with group IR, Longa score and cerebral infarct volume were significantly decreased, the percentage of novel object exploration and discrimination index were increased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was up-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were increased in group P ( P<0.05), and no significant change was found in the parameters mentioned above in group LY ( P>0.05). Compared with group P, Longa score and cerebral infarct volume were significantly increased, the percentage of novel object exploration and discrimination index were decreased, the expression of p-PI3K, p-Akt, PSD-95 and SYN in hippocampal tissues was down-regulated, and the dendritic length and dendritic spine density of hippocampal neurons were decreased in group LY ( P<0.05). Conclusions:Pre-injection of young rat plasma can attenuate cognitive dysfunction after cerebral I/R in aged rats, and the mechanism is related to activation of hippocampal PI3K/Akt signaling pathway and improvement in synaptic plasticity.

Exploration and application of "internet + mobile medicine" in the process management of standardized residency training of obstetrics and gynecology / 中华医学教育探索杂志

Objective:To assess the application effect of "internet + mobile medicine" on the process management of standardized residency training of obstetrics and gynecology.Methods:A total of 43 teachers including 14 administrators and 29 instructors who were not directly responsible for management, and 41 residents who participated in the standardized training in our base were enrolled as research objects. The data of process management were sorted by internet technology, and combined with personal wishes and casting lots, the residents were divided into two groups: the control group ( n=21) adopted traditional way while the observation group ( n=20) used mobile medicine for process management. By conducting multi-dimensional questionnaire and data comparison, we analyzed the evaluation of teachers and residents, the scores of different stage of residents, and the satisfaction of cervical cancer postoperative patients to medical care under different process management mode. SPSS 22.0 software was used for t test and chi-square test. Results:The application of "internet + mobile medicine" in standardized residency training obtained positive evaluation both by teachers and residents, and the ratio of considering "necessary" to reform the traditional residency training management mode in residents [95.1%(39/41)] and administrators [92.9%(13/14)] were both higher than that in instructors [62.1%(18/29)]. And 78.6%(11/14) of the administrators believed that cloud data management took less time. After 6 months of process management by different modes, the clinical diagnosis and treatment ability and skill operation ability scores of observation group were higher than those of control group [(93.6±5.6) vs. (89.4±5.7); (89.6±8.8) vs. (84.0±8.7)]. The "overall medical satisfaction rate" of cervical cancer patients was relatively high in both groups [100%(30/30) vs. 93.3%(28/30)], and the "very satisfied rate" of patients in the mobile medical group was higher than that in the traditional group [86.7%(26/30) vs. 63.3%(19/30)].Conclusion:The application of "internet + mobile medicine" is conducive to strengthening the process management and optimizing the quality of standardized residency training management of obstetrics and gynecology.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: A prospective Chinese cohort study / 中华医学杂志(英文版)

BACKGROUND@#Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA).@*METHODS@#A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups.@*RESULTS@#A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment ( P  = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred.@*CONCLUSIONS@#COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Mechanism of Marsdenia tenacissima against ovarian cancer based on network pharmacology and experimental verification / 中国中药杂志

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.

Recent Research Progress of Extramedullary Plasmacytoma --Review / 中国实验血液学杂志

Extramedullary plasma cell tumor (EMP) is a kind of plasma cell tumor, and its pathogenesis is not completely clear. According to whether it is independent of myeloma disease, it can be divided into primary and secondary EMP, which have different biological and clinical characteristics. Primary EMP has low invasion, fewer cytogenetic and molecular genetic abnormalities and good prognosis, and surgery and / or radiotherapy are the mainly treatments. Secondary EMP, as the extramedullary invasive progression of multiple myeloma (MM), is often accompanied by high-risk cellular and molecular genetic abnormalities and poor prognosis, chemotherapy, immunotherapy and hematopoietic stem cell transplantation are the mainly treatment. This paper reviews the latest research progress of EMP in the pathogenesis, cytogenetics molecular genetics and treatment, so as to provide reference for clinical work.

Study on the obesity-related factors among primary and middle school students in Hangzhou / 中华流行病学杂志

Objective: To explore the obesity-related factors among primary and middle school students in Hangzhou. Methods: A stratified random cluster sampling cross-sectional study was conducted using Hangzhou city's 2016-2020 annual school health survey data. Finally, 9 213 primary and secondary school students with complete data were selected as the research objects. The standard of Overweight and Obesity Screening for School-age Children and Adolescents (WS/T 586-2018) was used to verify students' obesity. SPSS 25.0 software was applied to conduct statistical analysis on the related factors of obesity. Results: The overall obesity detection rate among primary and middle school students in Hangzhou was 8.52%. The results of logistic regression analysis showed that inadequate sleep (OR=6.507, 95%CI: 2.371-17.861, P<0.001), 3- hours (OR=5.666, 95%CI: 2.164-14.835, P<0.001) and ≥4 hours (OR=7.530, 95%CI: 2.804-20.221, P<0.001) of watching video every day in the past week, being beaten and scolded by parents in the past week (OR=1.627, 95%CI: 1.161-2.280, P=0.005), parents often reduce students' exercise time in order to let students have more time to study in the past week (OR=3.310, 95%CI: 1.243-8.819, P=0.017), age 16-18 years old (OR=0.137, 95%CI: 0.050-0.374, P<0.001), often suffering from campus violence in the past week (OR=0.332, 95%CI: 0.141-0.783, P=0.012), 1 hour of watching video every day in the past week (OR=0.023, 95%CI: 0.006-0.083, P<0.001), sometimes having breakfast (OR=0.151, 95%CI: 0.058-0.397, P<0.001) and eating breakfast every day (OR=0.020, 95%CI: 0.005-0.065, P<0.001) in the past week, eating vegetables and fruits sometimes (OR=0.015, 95%CI: 0.010-0.023, P<0.001) and every day (OR=0.020, 95%CI: 0.008-0.053, P<0.001) in the past week, eating sweet food sometimes (OR=0.089, 95%CI: 0.035-0.227, P<0.001) and every day (OR=2.568, 95%CI: 1.632-4.041, P<0.001) in the past week, eating fried food sometimes (OR=0.274, 95%CI: 0.094-0.800, P=0.018) in the past week, and having three physical education classes every week (OR=0.156, 95%CI: 0.057-0.423, P<0.001) were the main related factors affecting the occurrence of obesity in primary and secondary school students. Conclusions: With the higher obesity prevalence among primary and middle school students in Hangzhou, parents and teachers should strengthen health education for primary and middle school students, help children develop scientific eating behavior, develop positive and healthy living habits of children, and effectively prevent overweight/obesity in primary and middle school students.

SmHPPR1 from Salvia miltiorrhiza regulated the biosynthesis of salvianolic acids / 药学学报

italic>Salvia miltiorrhiza Bunge is a traditional Chinese medicinal herb widely used to treat cardiovascular and cerebrovascular diseases at clinic. Its main water-soluble components are rosmarinic acid (RA) and salvianolic acid B (SAB), which are produced by phenylpropanoid pathway. 4-Hydroxyphenylpyruvate reductase (HPPR) is a key enzyme in phenylpropanoid metabolism pathway. SmHPPR1 was cloned from S. miltiorrhiza and was constructed into plant expression vector pJR-SmHPPR1. On this basis, SmHPPR1 transgenic Arabidopsis plants were induced and the content of 4-hydroxyphenyllactic acid (pHPL) was determined. SmHPPR1-overexpressing (SmHPPR1-OE) hairy roots of S. miltiorrhiza were obtained and the concentration of active components and transcriptome analysis were performed. The results showed that the concentration of pHPL in SmHPPR1 transgenic Arabidopsis T1 was 0.594 mg·g-1 dry weight. The concentration of RA, SAB and total salvianolic acid in SmHPPR1-OE-3 hairy roots were 1.09, 1.29, 1.15 times of that in control-3, respectively, and the content of Danshensu was 36.26% of that in control-3. Transcriptomic analysis revealed that overexpression of SmHPPR1 caused the upregulation of other phenylpropanoid pathway genes like SmTAT2. Protein-protein interaction indicated CYT (TR74706_c0_g1), NADP+ (TR26565_c0_g1) and NADP+ (TR68771_c0_g1) is the central node of the network and participated in metabolic process and cellular process. The tracking work in this study proved that SmHPPR1 could catalyze the reduction of 4-hydroxyphenylpyruvic acid to 4-hydroxyphenyllactic acid in SmHPPR1 transgenic Arabidopsis, and SmHPPR1-overexpressing in hairy roots of S. miltiorrhiza could increase the concentration of salvianolic acids through synergistically regulating other pathway genes.

Evaluation of Clinical Efficacy of Shengmaisan Granules in Inhibiting Myocardial Fibrosis in Patients with Chronic Heart Failure with Qi-Yin Deficiency Syndrome Based on CMR / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.

Lung protective effect of driving pressure-guided lung protective ventilation strategy combined with pressure-controlled ventilation in elderly patients undergoing thoracoscopic radical resection of lung cancer / 肿瘤研究与临床

Objective:To investigate the lung protective effect of driving pressure-guided lung protective ventilation strategy (LPVS) combined with pressure-controlled ventilation (PCV) in elderly patients undergoing thoracoscopic radical resection of lung cancer.Methods:One hundred elderly patients scheduled for thoracoscopic radical resection of lung cancer from April 2021 to April 2022 in the Second Hospital of Shanxi Medical University were selected. Patients were aged 60-80 years old and American Society of Anesthesiologists (ASA) classification Ⅰ-Ⅱ. All patients were divided into 4 groups by using the random number table method, with 25 cases in each group. Group A received volume-controlled ventilation (VCV) + 5 cm H 2O (1 cm H 2O = 0.098 kPa) PEEP, group B received PCV+5 cm H 2O PEEP, group C received VCV+driving pressure-guided individualized PEEP, and group D received PCV+driving pressure-guided individualized PEEP. The arterial oxygen partial pressure (PaO 2) was recorded before one-lung ventilation (OLV) (T 0), 30 min after OLV (T 1) and 60 min after OLV (T 2). The serum concentrations of neutrophil elastase (NE) in radial artery blood samples of patients were measured at T 0 and 10 min after the end of OLV (T 3). The occurrence of postoperative pulmonary complications (PPC) within 5 d after surgery was recorded. Results:The PaO 2 of group A and B at T 1 [(135±50), (146±51) mmHg (1 mmHg = 0.133 kPa)] and T 2 [(137±46), (143±47) mmHg] were lower than those of group C and group D at T 1 [(168±27), (190±30) mmHg] and T 2 [(180±30), (183±24) mmHg] (all P < 0.05). The incidence of PPC within 5 d after surgery in group A was higher than that in group D [36% (9/25) vs. 4% (1/25)] ( P = 0.005). The concentration of NE at T 3 in group A [(202.8±9.7) ng/ml] was lower than that in group B, C and D [(182.5±12.0), (180.0±10.3), (160.6±13.0) ng/ml] ( P < 0.05). Conclusions:During OLV, driving pressure-guided LPVS combined with PCV can not only improve oxygenation, but also show obvious advantages in reducing inflammatory response. It is a safe and effective intraoperative ventilation strategy for elderly patients undergoing thoracoscopic radical resection of lung cancer.

A study on the correlation between serum branched-chain amino acid levels and disease severity in alcoholic liver cirrhosis patients / 中华临床营养杂志

Objective:To characterize the serum branched-chain amino acid (BCAA) and aromatic amino acid profiles in patients with alcoholic liver cirrhosis (ALC).Methods:Forty patients with ALC were recruited into the study group, twenty patients with hepatitis B-induced liver cirrhosis (HBV-LC) and ten healthy subjects (HC) were recruited as controls from August 2017 to August 2019 in Beijing YouAn Hospital, Capital Medical University. The serum concentrations of isoleucine, leucine, valine, phenylalanine and tyrosine were determined by ultra-fast liquid chromatography tandem quadrupole mass spectrometry (LC-MS/MS) and Fischer ratio was also calculated for the three groups.Results:The serum isoleucine concentration in the study group [(23.74±8.81) μmol/L] was significantly lower than that in the HBV-LC group [(30.85±8.70) μmol/L, P = 0.031] and the HC group [(61.51±23.06) μmol/L, P < 0.01]. The serum leucine concentration in the study group [(127.99±38.54) μmol/L] was significantly lower than that in the HC group [(153.70±11.88) μmol/L, P = 0.036] and was not significantly different compared with the HBV-LC group [(126.70±31.00) μmol/L, P = 0.890]. The concentration of valine in the study group was (39.56±10.51) μmol/L, which was significantly lower than that in the HBV-LC group [(124.71±45.00) μmol/L, P < 0.01] and the HC group [(164.23±37.16) μmol/L, P < 0.01]. The concentration of phenylalanine in the study group was (141.19±29.35) μmol/L, which was significantly higher than that in the HBV-LC group [(116.07±21.52) μmol/L, P = 0.001] and the HC group [(80.94±7.16) μmol/L, P < 0.001]. Fischer ratio in the study group was significantly lower (1.17±0.34) than that in the HBV-LC group (2.07±0.66, P < 0.01) and the HC group (3.36±0.50, P < 0.01). Along with liver function deteriorating from Child-Pugh grade A to C, the isoleucine, leucine and valine levels in the study group decreased gradually. Fischer ratios in subgroups with Child-Pugh grade C and B liver function were 1.01±0.22 and 1.15±0.32, respectively, significantly lower than that in Child-Pugh grade A subgroup (1.52±0.38, P = 0.001 and P = 0.008). Conclusions:Serum BCAA levels and Fischer ratio decreased significantly in ALC patients, which were more prominent in patients with Child-Pugh grade B and C liver function. In Child-Pugh grade A patients, the decline of Fischer ratio developed earlier than the decrease of serum albumin. Monitoring of BCAA level changes should be an important component in nutritional intervention in ALC patients.

Effect of azacitidine on HOXA9 gene expression and biological behaviors of A375 melanoma cells / 中华皮肤科杂志

Objective:To investigate the effect of the methyltransferase inhibitor azacitidine (5-azaC) on the expression of homeobox A9 (HOXA9) gene in, as well as proliferation, invasion and migration of A375 cells.Methods:In vitro cultured A375 cells were treated with 5-azaC at various concentrations of 1, 5, 10 and 20 μmol/L, while routinely cultured A375 cells receiving no drug intervention served as control group. Methylation-specific PCR was performed to analyze methylation status of the HOXA9 gene promoter region after the treatment with different concentrations of 5-azaC, in order to screen the optimal concentration of 5-azaC for following experiments. Cell counting kit-8 (CCK8) assay was conducted to evaluate the proliferation of A375 cells, Transwell and wound healing assays were performed to estimate the invasion and migration of A375 cells, and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of HOXA9 in A375 cells after 5-azaC treatment. Two-independent-sample t test was used for comparisons between two groups. Results:Methylation was observed in the HOXA9 gene promoter region in A375 cells in the control group. After 5-azaC treatment, methylated and unmethylated states coexisted in the HOXA9 gene promoter region in A375 cells, and the higher the concentration of 5-azaC, the higher the degree of demethylation of the HOXA9 gene. Therefore, 20 μmol/L 5-azaC was selected to treat A375 cells for 72 hours, which served as 5-azaC treatment group in subsequent experiments. Compared with the control group, the 5-azaC treatment group showed significantly decreased cellular proliferative ability (72.46% ± 2.19% vs. 100%, t = 28.09, P < 0.001) , significantly decreased number of invasive cells (242.70 ± 29.19 vs. 466.00 ± 22.65, t = 10.47, P < 0.001) , significantly decreased migratory ability (27.56% ± 2.74% vs. 35.69% ± 2.50%, t = 3.79, P = 0.019) , significantly increased HOXA9 mRNA expression (1.73 ± 0.28 vs. 1.01 ± 0.15, t = 3.93, P = 0.017) , and significantly increased HOXA9 protein expression (0.62 ± 0.03 vs. 0.50 ± 0.01, t = 3.82, P = 0.019) . Conclusion:5-azaC can inhibit the proliferative, invasive and migratory ability of A375 melanoma cells, and one of the possible mechanisms underlying this process may be that 5-azaC reverses the methylation in the HOXA9 gene promoter region, activates HOXA9 gene expression, and participates in the regulation of biological behaviors of melanoma cells.

Role of BDNF/TrkB signaling pathway in pre-injection of young rat plasma-induced reduction of sevoflurane-caused cognitive dysfunction in aged rats / 中华麻醉学杂志

Objective:To evaluate the role of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) signaling pathway in pre-injection of young rat plasma-induced reduction of sevoflurane-caused cognitive dysfunction in aged rats.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 18 months, weighing 550-650 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S), young rat plasma group (group Y) and BDNF/TrkB signaling pathway inhibitor K252a group (group K). The plasma 100 μl obtained from 3-month-old young rats was injected via the tail vein in group Y and group K, while the equal volume of normal saline was given via the tail vein in group C and group S, twice a week, for 4 weeks.In S, Y and K groups, 3% sevoflurane was inhaled for 3 h starting from the end of treatment, and BDNF/TrkB signaling pathway inhibitor K252a was injected via the tail vein before anesthesia in group K. The open field test and Morris water maze test were performed at 3 days after anesthesia to assess the spontaneous motor ability and cognitive function.Then the rats were sacrificed, and the hippocampal tissues were isolated for determination of the expression of BDNF, phosphorylated TrkB (p-TrkB), postsynaptic dense protein-95 (PSD-95) and synaptic vesicle protein (SYN) (by Western blot), dendritic length and dendritic ridge density of neurons in hippocampal CA1 area (by Golgi staining), and the number of synapses and length of synaptic active area (with a transmission electron microscope). Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-TrkB, BDNF, PSD-95 and SYN was down-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were decreased in group S ( P<0.05). Compared with group S, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-TrkB, BDNF, PSD-95 and SYN was up-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were increased in group Y ( P<0.05). Compared with group Y, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-TrkB, BDNF, PSD-95 and SYN was down-regulated, and the dendritic length, dendritic ridge density, the number of synapses and length of synaptic active area were decreased in group K ( P<0.05). Conclusions:The mechanism by which pre-injection of young rat plasma reduces sevoflurane-induced cognitive dysfunction is related to activation of BDNF/TrkB signaling pathway and improvement in synaptic plasticity in the hippocampus of aged rats.

Study of clinical characteristics in patients with gp210 antibody-positive primary biliary cholangitis / 中华肝脏病杂志

Objective: To analyze the clinical characteristics and prognostic value of liver function in a large samples of patients with anti-glycoprotein 210 (gp210 antibody) positive primary biliary cholangitis (PBC). Methods: A retrospective study was performed on 931 PBC cases in Beijing You'an Hospital affiliated to Capital Medical University from 2010 to 2019. According to the detection of gp210 antibody, 318 cases were divided into gp210 antibody positive group (positive group) and 613 cases were divided into gp210 antibody negative group (negative group). The differences in demographic, medical history, clinical indicators, B-ultrasound and pathological indicators as well as the histopathological basis were compared between the two groups. SPSS 16.0 software was used for statistical analysis. Measurement data were analyzed by t-test or rank sum test, and enumeration data by χ2 test. Multivariate analysis was used for logistic test, and and survival analysis was used for prognosis. Results: The positive and the negative groups were compared. The ratio of male to female was significantly higher in positive than negative group (1:5.35 vs. 1:9.73, P＜0.05), and the difference was statistically significant. The proportion of hormone use in history of past diagnosed and treated was higher in positive than negative group (12.9% vs. 3.47%, P＜0.05), and the difference was statistically significant. The detection of biochemical indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) were higher in positive than the negative group (51.1 U/L vs. 41.1 U/L, 62.6 U/L vs. 49.6 U/L, 24.1 μmol/L vs. 17.9 μmol/L, 228.3 U/L vs. 169.6 U/L, 203.9 U/L vs. 147.6 U/L), (P＜0.05), and the differences were statistically significant. Antinuclear antibody (ANA)-positive rate, high titer ratio and immunoglobulin G (IgG) levels were higher in positive than negative group (95.2% vs. 81.6%, 69.7% vs. 48.8%, 17.2 g/L vs. 16.2 g/L), (P＜0.05), and the differences were statistically significant. The incidence of liver failure was higher in positive than negative group (P＜0.05). CK7 and inflammation score were higher in positive group than negative group in liver histopathological observations (0.83±0.53 vs. 0.28±0.47; 1.06±0.39 vs. 0.54±0.65), (P＜0.05), and the differences were statistically significant. Conclusion: The illness condition of patients with gp210 antibody positive PBC is more severe than patients with gp210 antibody negative PBC, and the incidence of liver failure is significantly increased. Cholangiocytes may be the histopathological basis of the clinical characteristics of gp210 antibody positive PBC patients.

Association between clinicopathological characteristics and gene mutations in 94 cases of cutaneous melanoma / 中华皮肤科杂志

Objective:To investigate associations between clinicopathological characteristics and mutations in susceptibility genes in cutaneous melanoma (CMM) .Methods:A total of 94 patients with confirmed CMM were collected from People′s Hospital of Xinjiang Uygur Autonomous Region from January to December in 2019, and their clinical and histopathological characteristics were retrospectively analyzed. In 48 paraffin-embedded melanoma tissue specimens, Sanger sequencing was performed to detect mutations in the BRAF, NRAS, c-KIT genes and the promoter region of human telomerase reverse transcriptase (hTERT) gene, and the association between gene mutations and clinicopathological characteristics was analyzed. Measurement data were compared using t test, and enumeration data were compared using chi-square test or Fisher′s exact test. Results:Among the 94 patients with CMM, there were 46 (48.9%) males and 48 (51.1%) females, with the age being 58.5 ± 16.0 years; 41 (43.6%) patients were of Han nationality, and 53 (56.4%) were of ethnic minorities. Skin lesions were located at the acral sites in 50 (53.2%) patients, including 27 (28.7%) of Han nationality; non-acral skin lesions occurred in 44 (46.8%) , including 14 (31.8%) of Han nationality; there was a significant difference in the nationality distribution between the acral CMM group and non-acral CMM group ( χ2 = 5.25, P = 0.022) . Histopathological examination showed CMM of Clark grades Ⅳ or Ⅴ in 41 (43.6%) cases, ulcers in 52 (55.3%) cases, and lymph node metastasis in 32 (34.04%) cases at the first clinic visit. Gene sequencing revealed BRAF gene mutations in 11 (22.9%) of 48 cases, including c.1799 T>A (p.V600E) , c.1790 T>A (p.L597Q) and c.1394 C>T (p.S465F) ; NRAS gene mutation c.182 A>G (p.Q61R) was identified in 5 (10.4%) cases; c-KIT gene mutations were identified in 6 (12.5%) cases, including c.1727 T>C (p.L576P) and c.1669 T>C (p.W557R) ; mutations in the promoter region of hTERT gene were identified in 7 (14.6%) cases, including 4 cases with a mutation at 124 bp upstream of the ATG start codon (C228T) and 3 cases with a mutation at 146 bp upstream of the ATG start codon (C250T) . Among 26 patients aged < 60 years, BRAF gene mutations were found in 9, and the incidence of BRAF gene mutations was significantly higher in the patients aged < 60 years than in those aged ≥ 60 years (2/22, P < 0.05) , but significantly lower in the patients with acral CMM (3/27) than in those with non-acral CMM (8/21, P < 0.05) ; the incidences of the NRAS, c-KIT and hTERT gene mutations were all significantly higher in the patients with lymph node metastases (3/10, 4/10, 4/10, respectively) than in those without (2/38, 2/38, 3/38, respectively, all P < 0.05) . Conclusion:CMM lesion locations significantly differed among different ethnic groups; the BRAF gene mutation was associated with the age of patients and lesion locations of CMM; NRAS, c-KIT gene mutations and hTERT promoter mutations were closely related to lymph node metastasis.

Chemical genetics technology regulates the activity of GLP-1 neurons and its effect on appetite / 中华内分泌代谢杂志

Objective:To conduct a glucagon like peptide-1(GLP-1)controllability model rat by chemical genetics, and observe the impact of GLP-1 neuron excitability on appetite.Methods:Fifteen rats were evenly divided into Green fluorescent protein(GFP)group, HM3D group, and HM4D group. Various combinations of adeno-associated virus(rAAV)were injected into the nucleus tractus solitarius(NTS). rAAV-GLP-1-cre and rAAV-GFP-dio were administered in rats of GFP group. The rats of HM3D group were injected with rAAV-GLP-1-cre and rAAV-HM3D-mCherry-dio while rAAV-GLP-1-cre and rAAV-HM4D-mCherry-dio were injected in rats of HM4D group . The optimal dose of clozapine N-oxide(CNO)was selected based on feeding behavior and body weight changes of rats after intraperitoneal injection of different doses of CNO. The controllability of GLP-1 neurons was confirmed by comparing with intraperitoneal injection of saline. The number of activated GLP-1 neurons in the NTS area and the expression of POMC neurons in the hypothalamus were detected 30 minutes after CNO injection.Results:GLP-1 neurons in the NTS area of rats were successfully labeled. The rat of HM3D group revealed a decrease in food intake( P=0.021)while the rat of HM4D group showed an increase( P=0.002), when given 1 mg/kg of CNO, no changes at the dose of 0.5 mg/kg and 3.0 mg/kg. Immunofluorescence showed that the activity of GLP-1 neurons in NTS of GFP group was lower than that of HM3D group( P=0.022), and higher compared with that of the HM4D group( P=0.049). The expression of GLP-1 neurons in NTS and POMC neurons in the hypothalamus of the HM3D group after intraperitoneal injection of CNO was also higher than that in the HM4D group( P=0.003). Conclusion:Using chemical genetics technology, GLP-1 controllability model rat could be successfully established via injecting varying combinations of rAAV into the NTS area of rat. Injection of 1 mg/kg CNO can effectively activate or inhibit the neuron to regulate appetite.