The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells / 中华创伤杂志(英文版)

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Effect of Shao's five-needle therapy pretreatment on airway inflammatory response in asthmatic rats based on ROS/TXNIP/NLRP3 pathway / 中国针灸

OBJECTIVES@#To explore the possible mechanism of Shao's five-needle therapy pretreatment on relieving airway inflammatory response in asthmatic rats.@*METHODS@#Forty SPF-grade SD rats were randomly divided into a blank group, a model group, an acupuncture group, and a medication group, with 10 rats in each group. Except the blank group, asthma model was established by aerosol inhalation of ovalbumin in the other 3 groups. The rats in the acupuncture group were treated with acupuncture at "Dazhui" (GV 14) and bilateral "Feishu" (BL 13) and "Fengmen" (BL 12), with each session lasting for 20 min. Acupuncture was given before each motivating, once daily for 7 consecutive days. The rats in the medication group were treated with intraperitoneal injection of dexamethasone sodium phosphate solution before each motivating, once daily for 7 days. General situation of the rats was observed in each group; ELISA method was used to detect the levels of inflammatory cytokines interleukin (IL)-1β and IL-18 in serum; immunofluorescence staining method was performed to assess the expression of reactive oxygen species (ROS) in lung tissues; Western blot method was used to measure the protein expression of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 in lung tissues.@*RESULTS@#The rats in the blank group exhibited normal behavior, while those in the model group showed signs of respiratory distress, ear scratching, cheek rubbing, and dysphoria. Compared with the model group, the rats in the acupuncture group and the medication group showed stable respiration and relatively agile responses. Compared with those in the blank group, the serum levels of IL-18 and IL-1β were elevated (P<0.01), the expression intensity of ROS was increased, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were increased (P<0.01) in the model group. Compared with those in the model group, the serum levels of IL-18 and IL-1β were reduced (P<0.01), the expression intensity of ROS was lowered, and the protein expressions of TXNIP, NLRP3, ASC and Caspase-1 in lung tissues were reduced (P<0.01) in the acupuncture group and the medication group. Compared with the medication group, the protein expression of ASC in lung tissue was reduced in the acupuncture group (P<0.05).@*CONCLUSIONS@#Pretreatment of Shao's five-needle therapy could alleviate airway inflammatory response in asthmatic rats by reducing ROS levels and decreasing the aggregation and activation of pathway-related proteins in the ROS/TXNIP/NLRP3 pathway, ultimately leading to decreased secretion of IL-1β and IL-18. This mechanism may contribute to the effectiveness of Shao's five-needle therapy in preventing and treating asthma.

Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking / 中国中药杂志

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1β), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

Semen parameters in men recovered from COVID-19 / 亚洲男科学杂志(英文版)

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Study on mechanism of Tibetan medicine Zuomua Decoction in treatment of hypertension based on network pharmacology and molecular docking technology / 中国中药杂志

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.

Portable Low-Cost MRI System Based on Permanent Magnets/Magnet Arrays

Portable low-cost magnetic resonance imaging (MRI) systems have the potential to enable “point-of-care” and timely MRI diagnosis, and to make this imaging modality available to routine scans and to people in underdeveloped countries and areas. With simplicity, no maintenance, no power consumption, and low cost, permanent magnets/magnet arrays/magnet assemblies are attractive to be used as a source of static magnetic field to realize the portability and to lower the cost for an MRI scanner. However, when taking the canonical Fourier imaging approach and using linear gradient fields, homogeneous fields are required in a scanner, resulting in the facts that either a bulky magnet/magnet array is needed, or the imaging volume is too small to image an organ if the magnet/magnet array is scaled down to a portable size. Recently, with the progress on image reconstruction based on non-linear gradient field, static field patterns without spatial linearity can be used as spatial encoding magnetic fields (SEMs) to encode MRI signals for imaging. As a result, the requirements for the homogeneity of the static field can be relaxed, which allows permanent magnets/magnet arrays with reduced sizes, reduced weight to image a bigger volume covering organs such as a head. It offers opportunities of constructing a truly portable low-cost MRI scanner. For this exciting potential application, permanent magnets/magnet arrays have attracted increased attention recently. A magnet/magnet array is strongly associated with the imaging volume of an MRI scanner, image reconstruction methods, and RF excitation and RF coils, etc. through field patterns and field homogeneity. This paper offers a review of permanent magnets and magnet arrays of different kinds, especially those that can be used for spatial encoding towards the development of a portable and low-cost MRI system. It is aimed to familiarize the readers with relevant knowledge, literature, and the latest updates of the development on permanent magnets and magnet arrays for MRI. Perspectives on and challenges of using a permanent magnet/magnet array to supply a patterned static magnetic field, which does not have spatial linearity nor high field homogeneity, for image reconstruction in a portable setup are discussed.

Correlation between circulating tumor cells and clinicopathological features of early breast cancer / 中南大学学报(医学版)

To investigate the correlation between the number of peripheral blood circulating tumor cells (CTCs) and clinicopathological features of early breast cancer. 
 Methods: The clinical and pathological data from 100 patients with early breast cancer treated by a breast cancer treatment team in the Department of Breast Surgery, Second Xiangya Hospital, Central South University, were collected from January 2017 to December 2018. For these patients, their peripheral blood CTCs were detected, enumerated and typed by CanpatrolTM CTC assay.
 Results: The positive rate of CTCs was 90% in peripheral blood of patients with early breast cancer, and the majority of molecular phenotypes was hybrid CTCs (55.6%). The positive rate of CTCs was only related to the pathological type of tumor (P<0.05), but not to other clinicopathological features. No correlation between clinicopathological features and the total number of CTCs, the number of epithelial CTCs or the number of hybrid CTCs was found. However, the number of mesenchymal CTCs was significantly correlated with the expression of hormone receptors and Ki-67 (r=0.200, P<0.05), and there was a significant correlation between the proportion of mesenchymal CTCs and the expression level of Ki-67 (r=0.213, P<0.05).
 Conclusion: The number of CTCs is not correlated with all clinicopathological features, but patients with negative hormone receptor and high expression of Ki-67 probably have more hybrid CTCs.

Tumor necrosis factor-α and transforming growth factor-β balance liver stem cell differentiation in cholestatic cirrhosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in mice with cholestatic cirrhosis and their role in regulating the balance of liver stem cell differentiation.</p><p><b>METHODS</b>Balb/c mice were subjected to bile duct ligation (BDL), and serum biochemical parameters were measured and hepatic histopathology was observed using HE staining to evaluate the modeling of cholestatic cirrhosis. Immunohistochemistry and Western blotting were used to detect the changes of TNF-α and TGF-β in the mice after modeling. Mouse embryonic hepatic stem cells (HP14-19) were treated with different concentrations of TNF-α and TGF-β, and the cell differentiation was assessed using Western blotting, real-time PCR, and PAS staining.</p><p><b>RESULTS</b>The mice receiving BDL showed significantly increased blood biochemical parameters (P<0.05), and HE staining revealed obviously increased collagen fibers in the liver with significantly increased expressions of TNF-α and TGF-β (P<0.05). In HP14-19 cells, induction with TNF-α and TGF-β for 3 days did not cause significant changes in cell differentiation, but induction for 5 days resulted in significantly increases intensity of PAS staining in the cells. The cells induced with 20, 40, and 80 ng/mL TNF-α for 5 days exhibited a significantly stronger expression of cytokeratin 18 than cytokeratin 19 (P<0.05), while induction with 20, 40, and 80 ng/mL TGF-β produced opposite changes in cytokeratin 18 and cytokeratin 19 expressions. Further induction of the cells with TNF-α and TGF-β for 10 days, did not alter the expression patterns of cytokeratin 18 and cytokeratin 19 observed on day 5, but their protein expression levels and PAS staining intensity of the cells were enhanced and their mRNA expressions became lowered.</p><p><b>CONCLUSION</b>Common bile duct ligation can induce conditions simulating cholestatic cirrhosis in mice. TNF-α and TGF-β are elevated in cholestatic cirrhosis and play opposite roles in regulating the differentiation balance of liver stem cells: the former promotes the differentiation of liver stem cells into hepatocytes, while the latter promotes the cell differentiation into colangiocytes.</p>

Changes in autophagy during maturation and differentiation of Hepa1-6 cells induced by all-trans retinoic acid / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of all-trans retinoic acid (ATRA) on the maturation, differentiation and autophagy of Hepa1-6 cells.</p><p><b>MONTHOD</b>Hepa1-6 cells were treated with 0.1, 1, and 10 µmol/L ATRA, and the changes in the expressions of hepatic specific markers were detected using real-time PCR and Western blotting. Indocyanine green (ICG) and periodic acid-schiff (PAS) staining was used to assess the functional maturation of Hepa1-6 cells, and the cell-cell junction and autophagy were observed under transmission electron microscopy to determine the optimal concentration of ATRA for treatment. The expressions of autophagy-related markers in the cells were detected using Western blotting, and confocal microscopy was used to observe the autophagic flow in the cells transfected with ptfLC3 plasmid.</p><p><b>RESULTS</b>Compared with the control cells, the hepatocytes treated with ATRA showed a concentration-dependent decrease in AFP expression and increase in the expressions of ALB, CK18, TAT and ApoB. ICG and PAS staining revealed significantly increased number of positive cells after ATRA treatment. Following ATRA treatment, the cells exhibited obviously increased tight junctions, cytoskeleton and number of autophagosomes under transmission electron microscopy. ATRA treatment resulted in significantly increased the expressions of autophagy-related markers LC3-II, Beclin-1, RAB7 and P62 and also an increased ratio of LC3-II/LC3-I(P<0.05). Confocal microscopy revealed obviously increased green and red spots in the cells after ATRA treatment.</p><p><b>CONCLUSION</b>ATRA can induce the maturation and differentiation and enhance the level of autophagy in Hepa1-6 cells.</p>

Impact of gender and age on in-hospital mortality after coronary artery bypass graft / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of this study was to explore the association of gender and age on in-hospital mortality after coronary artery bypass graft (CABG) among the Chinese population.</p><p><b>METHODS</b>A total of 2682 patients (male: 2316, female: 366) who underwent CABG surgery were retrospectively investigated between January 1st, 1997 and December 31st, 2001 for perioperative risk factors and in-hospital mortality rate after CABG.</p><p><b>RESULTS</b>Preoperative comorbidity rate and postoperative complication rate were higher in women than that in men, although left ventricular ejection fraction was higher and the number of diseased vessels fewer in women than in men. The in-hospital mortality rate was three times higher in women than that in men (3.01% vs. 1.12%, P = 0.001), especially in the younger age group (2.6% vs. 0.5%, P = 0.001, risk-adjusted odds ratio 4.844, 95% CI: 1.549 - 15.142). In older patients, there was no notable difference in in-hospital mortality between the genders (3.7% for women vs. 2.4% for men, P = 0.383).</p><p><b>CONCLUSIONS</b>Chinese woman, especially in younger age, had a higher in-hospital mortality rate post CABG than that in men, suggesting that younger female gender is an independent risk factor for in-hospital mortality after CABG. Future studies are warranted to clarify the underlying mechanisms.</p>