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.

Laboratory diagnostics within a modular hospital at the time of Coronavirus disease 2019 (COVID-19) in Wuhan.

An outbreak of the so-called Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has been spreading rapidly nationwide in China since December 2019. Wuhan, Hubei Province, is the hardest-hit region, with a rise in confirmed cases and its hospitals overwhelmed. On 2nd February, 2020, Wuhan began to build a modular hospital to treat patients caught with mild illness. The mobile modular hospital is mainly composed of medical modules, technical support modules, ward units, living support units and transportation capacity under field conditions, and there are complete equipment and specialized personnel to treat patients. Due to the severity and particularity of SARS-CoV-2, taking granted from lessons learnt from mobile modular hospitals, we use the existing large venues to construct a new fixed modular hospital. As patients need to be treated and tested, it is important to develop a clinical laboratory in the modular hospital and ensure biosafety. The construction of a clinical laboratory in the modular hospital is faced with problems such as time pressure, limited site selection, high level of biosafety, lack of experience and so forth. This paper mainly discusses how to construct the clinical laboratory in the modular hospital quickly and safely and put it into use to provide testing service for patients under various limited conditions.

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.

Mechanism of SPRY1 methylation regulating natural aging of skin epidermal cells.

OBJECTIVE: To investigate the relationship among natural aging of epidermal cells, epigenetics, and SPRY1 methylation mechanism. METHODS: Immunohistochemistry, reverse transcription-PCR (RT-PCR), and Western blot were used to detect the expression of DNA methyltransferase 1 (DNMT1) and Sprouty1 (SPRY1) in skin epithelial cells from different age groups. An aging model of HaCaT cells was constructed. In HaCaT cells and their aging groups, DNMT1 and SPRY1 expression were detected by RT-PCR and WB. SPRY1 methylation status in epidermal cells from different age groups and HaCaT cells were detected by Methylation-Specific PCR (MS-PCR). RESULTS: The expression of DNMT1 and SPRY1 in skin epithelial cells from natural aging groups decreased with age; there was no significant difference in the expression of DNMT1 in HaCaT cells and the different age groups. The expression of SPRY1 in HaCaT cells was lower than it was in the aging groups. The methylation status of SPRY1 gradually decreased as the age of skin epidermal cells increased, while the methylation status of SPRY1 was not different between HaCaT cells and the aging group. CONCLUSION: DNMT1 is involved in the regulation of natural aging of skin epidermal cells but has a nominal role in our induced aging model. SPRY1 is involved in natural aging and induced aging of skin epidermal cells. The regulation of SPRY1 methylation is involved in the natural senescence of skin epidermal cells, while the induced aging of epidermal cells is nominally involved in the mechanism of SPRY1 methylation.

Necrostatin-1 Ameliorates Peripheral Nerve Injury-Induced Neuropathic Pain by Inhibiting the RIP1/RIP3 Pathway.

Necrostatin-1 is an inhibitor of necroptosis, a form of programmed cell death that has been reported to be involved in various neurological diseases. Presently, the role of necroptosis in neuropathic pain induced by peripheral nerve injury is still unclear. This study was focused on investigating the potential effects of necroptosis in the development and progression of neuropathic pain in a rat model and the possible neuroprotective effects of necrostatin-1 in neuropathic pain. The results indicated that the necroptosis-related proteins RIP1 and RIP3 significantly increased postoperation in the spinal cord in a neuropathic pain model and peaked 7 days postoperation, which was consistent with the time-dependent changes of hyperalgesia. Additionally, we found that peripheral nerve injury-related behavioral and biochemical changes were significantly reduced by necrostatin-1. In particular, hyperalgesia was attenuated, and the levels of RIP1 and RIP3 were decreased. Furthermore, the ultrastructure of necrotic cell death and neuroinflammation were alleviated by necrostatin-1. Collectively, these results suggest that necroptosis is an important mechanism of cell death in neuropathic pain induced by peripheral nerve injury and that necrostatin-1 may be a promising neuroprotective treatment for neuropathic pain.

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.

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.

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.

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.

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.

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.

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.

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.

[Effects of five Chinese herbs on human demodicid mites in vitro].

OBJECTIVE: To research the effects of five Chinese herbs of Artemisia argyi, Chimonanthus praecox, Agastache rugosa, pine needles and Osmamthus fragrans on human demodicid mites in vitro. METHODS: The human demodicid mites were acquired with the cellophane tape method. The ethanol heat reflux extractions were carried out on the 5 kinds of Chinese herbs to be studied and Stemona sessilifolia as the positive control, so as to get the herbal extracts. Next, the drug administration was carried out to the demodicid mites, and the inhibitory or killing effects of the 6 kinds of Chinese herbs above mentioned on the vermiform mites were observed under a microscope. It was considered to be dead when the bodies of the demodicid mites stopped moving. Besides, the duration from drug administration to death of the vermiform mites was recorded. RESULTS: Artemisia argyi, Chimonanthus praecox and Agastache rugosa could effectively inhibit and kill human demodicid mites. The effect of Artemisia argyi and Agastache rugosa was similar to the effect of Stemona sessilifolia, and the effect of Chimonanthus praecox was weaker than Stemona sessilifolia's effect. Among them, Agastache rugosa took a relatively short time (4.60 min ± 1.66 min) min and Osmamthus fragrans took the longest time (114.65min ± 80.14min) to Demodex folliculorum; Whereas, Artemisia argyi took the shortest time (3.56min ± 1.92 min) min and Osmamthus fragrans took the longest time (194.24min ± 134.96 min) min to Demodex brevis. CONCLUSIONS: The effects of Artemisia argyi and Agastache rugosa on human demodicid mites are similar to that of Stemona sessilifolia. The effects of Chimonanthus praecox and pine needles are weaker than that of Stemona sessilifolia. Osmamthus fragrans has no acaricidal effect.

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.

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.

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.

Application effect of severe ultrasound combined with extravascular lung water and intrathoracic blood volume in volume management of mechanical ventilation / 中国医师进修杂志

Objective:To explore the application effect of critical ultrasound combined with extravascular lung water (EVLW) and intrathoracic blood volume (ITBV) on volume management of mechanically ventilated patients.Methods:From May 2017 to January 2020, 98 patients treated with mechanically ventilated admitted to Hebei Petro China Central Hospital were selected and divided into two groups by random number table method, with 49 cases in each group. Both groups were treated with fluid resuscitation, the control group was guided by central venous pressure (CVP) and the observation group was guided by critical ultrasound combined with EVLW and ITBV. The acute physiology and chronic health score Ⅱ(APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores, hemodynamic indexes, respiratory system indexes , urine output and fluid intake at 6 h and 24 h after resuscitation and mechanical ventilation time, ICU stay, complications and prognosis were compared between the two groups.Results:The scores of APACHE Ⅱ and SOFA in the observation group at 6 h and 24 h after resuscitation were lower than those in the control group: 6 h after resuscitation: (22.02 ± 4.29) scores vs. (23.94 ± 3.56) scores, (10.02 ± 3.11) scores vs. (11.64 ± 2.30) scores; 24 h after resuscitation: (19.66 ± 2.85) scores vs. (21.78 ± 3.60) scores, (7.64 ± 2.15) scores vs. (9.83 ± 2.07) scores, the differences were statistically significant ( P<0.05). The mean arterial pressure (MAP) and CVP in the observation group at 6 h and 24 h after resuscitation were higher than those in the control group: 6 h after resuscitation: (69.44 ± 5.25) mmHg(1 mmHg=0.133 kPa) vs. (65.98 ± 4.33) mmHg, (13.64 ± 2.30) mmHg vs. (11.89 ± 3.07) mmHg; 24 h after resuscitation: (72.89 ± 4.69) mmHg vs. (69.26 ± 5.53) mmHg, (13.07 ± 2.15) mmHg vs. (11.89 ± 3.07) mmHg; the heart rate was lower than those in the control group: 6 h after resuscitation: (98.58 ± 9.32) bpm vs. (105.03 ± 8.76) bpm; 24 h after resuscitation: (94.97 ± 8.46) bpm vs.(101.44 ± 7.34) bpm, the differences were statistically significant ( P<0.05). The central venous oxygen saturation (ScvO 2) and oxygenation index (OI) in the observation group at 6 h and 24 h after resuscitation were higher than those in the control group: 6 h after resuscitation: 0.749 ± 0.043 vs. 0.711 ± 0.047, (258.18 ± 20.75) mmHg vs. (234.66 ± 25.42) mmHg; 24 h after resuscitation: (77.68 ± 4.09)% vs. (73.54 ± 4.23)%, (376.29 ± 22.39) mmHg vs. (234.66 ± 25.42) mmHg; the blood lactic acid was lower than that in the control group: 6 h after resuscitation: (3.04 ± 0.52) mmol/L vs. (4.22 ± 0.39) mmol/L; 24 h after resuscitation: (1.01 ± 0.34) mmol/L vs. (1.87 ± 0.41) mmol/L, the differences were statistically significant( P<0.05). The urine output at 6 h and 24 h in the observation group was higher than that in the control group: 6 h after resuscitation: (0.49 ± 0.08) ml/(kg·h) vs. (0.35 ± 0.06) ml/(kg·h); 24 h after resuscitation:(0.54 ± 0.05) ml/(kg·h) vs. (0.42 ± 0.07) ml/(kg·h); the fluid intake was lower than that in the control group: 6 h after resuscitation: (1 230.2 ± 562.3) ml vs. (1 782.4 ± 534.7) ml; 24 h after resuscitation: (3 065.5 ± 521.2) ml vs. (3 642.0 ± 507.8) ml; the mechanical ventilation time, and ICU stay in the observation group were lower than those in the control group: (3.3 ± 0.9) d vs. (5.0 ± 0.7) d, (9.7 ± 2.1) d vs. (10.9 ± 1.8) d, the differences were statistically significant ( P<0.05). There was no significant differences in complication rate and 28-day survival curve between the two groups ( P>0.05). Conclusions:Critical ultrasound combined with EVLW and ITBV has a good application effect on volume management of patients with mechanical ventilation, which can help maintain hemodynamic stability, improve oxygenation status.

Risks and intervention strategies of pulmonary embolism in children / 中国小儿急救医学

There are more and more cases of pulmonary embolism in children, most of whom have etiology or risk factors, and the clinical features are not specific.At present, there is a lack of large samples of clinical researches in children.The methods of evaluation, diagnosis and treatment of pulmonary embolism in children mostly refer to adult experience and standards.No unified standards are applied to children.This review analyzed the risks factors, diagnosis, evaluation and treatments of pulmonary embolism in children, in order to help clinicians judge and treat their patients.