Objective To study the role of glucagon-like peptide-1 (GLP-1) analogue liraglutide played in the proliferation of CD4+CD25 T cells in normal people and newly-onset type 1 diabetic patients,and to evaluate the possible immune regulatory role of liraglutide in the therapy of type 1 diabetes.Methods CD4+ CD25-T cells of 10 normal people and 10 newly-onset type 1 diabetic patients were separated from peripheral blood by MACS immunomagnetic beads and stimulated by Human T-Activator CD3/CD28 Dynabeads to proliferate.CFSE labeling technique was used to evaluate the proliferation of CD4+ CD25-T cells by flow cytometry.Liraglutide of different concentrations(0,25,50,and 100 nmol/ml) was added to the proliferation system,then the proliferation of CD4+CD25-T cell was measured.Results (1) Liraglutide suppressed the proliferation of CD4+ CD25-T cells from either normal people or type 1 diahetic patients with dose-dependent manner (P ＜ 0.05).(2) Under the different concentrationsofliraglutide,the proliferation ofCD4+CD25 T cells from diabetic patients was mueh more robust than that of normal people (P＜0.01).(3) The inhibitory effects of liraglutide on CD4+ CD25-T cells proliferation in normal people and diabetic patients were similar (P＞0.05).Conclusion The proliferation of CD4+ CD25 T cells in type 1 diabetic patients was more robust than normal people,which indicated cellular immune dysfunction in type 1diabetes.Liraglutide inhibits the proliferation of CD4+ CD25-T cells of type 1 diabetic patients in vitro.The immunosuppression effect of liraglutide may have potential value in the treatment of type 1 diabetes.

Objective:To evaluate the clinical efficacy and safety of compound glycyrrhizin combined with tripterygium wilfordii polyglycosides for psoriasis.Methods:Literature search was conducted in CNKI, Wanfang, VIP databases, Sinomed, PubMed, the Cochrane Library and Embase with the deadline of September 28th, 2020. The randomly controlled trials of compound glycyrrhizin combined with tripterygium wilfordii polyglycosides in treating psoriasis was included. The publication bias and methodology quality of RCTs were evaluated according to the Cochrane 5.0.1 bias risk assessment method. The RevMan 5.3 software was used for meta analysis.Results:Ten studies with 961 patients were included, with the experimental group ( n=486) and the control group ( n=475). The results of meta-analysis showed that the total effective rate [ OR=3.16, 95% CI (2.00-4.99), P<0.001], the cure rate [ OR=2.56, 95% CI (1.94-3.61), P<0.001], the recurrence rate [ OR=0.15, 95% CI (0.04-0.60), P=0.007], the total incidence of adverse reactions [ OR=0.53, 95% CI (0.34-0.82), P=0.004], the incidence of abnormal liver function [ OR=0.17, 95% CI (0.06-0.47), P=0.001] in the experimental group were better than those in the control group. There was no significant difference on the incidence of adverse reactions of digestive tract ( P>0.05) or lower extremity or facial edema ( P>0.05) between both groups. Conclusions:Compound glycyrrhizin combined with tripterygium wilfordii polyglycosides is effective in the treatment of psoriasis than tripterygium wilfordii polyglycosides alone, and can reduce the recurrence rate and the incidence of adverse reactions. However, a large number of large samples and high-quality studies are still needed.

Objective:To evaluate the feasibility of a new ultrasonic parameter to assess right ventricular-pulmonary artery (RV-PA) coupling in patients with acute pulmonary embolism (APE).Methods:A retrospective analysis was performed in 140 patients with APE diagnosed by computed tomography pulmonary angiography (CTPA) in the Second Affiliated Hospital of Harbin Medical University from August 2017 to June 2020. According to the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio cutoff value 0.40 mm/mmHg reported by the European Society of Cardiology in 2020, the patients were divided into the coupling group ( n=99) and the uncoupling group ( n=41). The conventional ultrasonic parameters of the 2 groups were measured, and then several ultrasonic parameter ratios were obtained. The new ultrasonic parameter, which can replace the TAPSE/PASP ratio, was screened out by Spearman correlation analysis, and ROC curve was plotted to calculate the diagnostic efficacy of this parameter. Results:①Compared with the coupling group, patients in the uncoupling group were older and more likely to be accompanied by dyspnea and venous thrombosis in the lower extremities (all P<0.05), but there was no significant difference in other general data(all P>0.05); ②Compared with the coupling group, tricuspid regurgitation velocity (TRV), tricuspid regurgitation pressure gradient(TRPG), PASP, right ventricle end-diastolic transverse diameter(RVTD), inferior vena cava(IVC) diameter and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity(E/e′), in the uncoupling group increased significantly (all P<0.05), and TAPSE, peak systolic velocity of tricuspid annulus(s′), TAPSE/PASP ratio, TAPSE/TRPG ratio, TAPSE/RVTD ratio and s′/TRPG ratio decreased significantly (all P<0.05); ③The TAPSE/TRPG ratio was highly correlated with TAPSE/PASP ratio ( rs=0.970, P<0.001); The TAPSE/TRPG ratio was still highly correlated with TAPSE/PASP ratio in the uncoupling and coupling groups ( rs=0.966, 0.922; all P<0.001). ④ROC analysis showed that the area under curve for TAPSE/TRPG in diagnosing RV-PA coupling was 0.992. At the cutoff of TAPSE/TRPG <0.625 mm/mmHg for indicating RV-PA coupling, the sensitivity and specificity were 97.6% and 92.9%, respectively. Conclusions:TAPSE/TRPG ratio can be used as a new ultrasonic parameter to reflect RV-PA coupling, which is helpful for clinical identification of APE patients with high risk and poor prognosis.

OBJECTIVE: To establish a method for in vitro expansion of human natural CD4⁺CD25⁺ T regulatory cell (Treg) cells for clinical study and immunotherapy. METHODS: Human natural CD4⁺CD25⁺ Treg were isolated from peripheral blood monocyte cells (PBMCs) by magnetic activated cell sorting (MACS) and expanded by CD3/CD28 expansion beads, IL-2 and rapamycin. The number and the viability of the freshly isolated and expanded Treg were detemined by trypan blue staining. The phenotype and the purity of the freshly isolated and expanded Treg were analyzed by FACS. Treg suppression activity was assessed by mixed lymphocyte reaction (MLR) assay. RESULTS: Human natural Treg were expanded up to 2 000 folds after 3 weeks in culture, and the activity was more than 97%. The expanded Treg retained Treg phenotype as shown by their freshly isolated counterparts, and the purity of CD4⁺CD25⁺FoxP3⁺ Treg was (94.22 ± 2.12)%. The expanded Treg demonstrated a similar potent suppression of both proliferating auto- and allo- CD4⁺CD25⁻ effector T cells in vitro in a cell number-dependent manner. CONCLUSION An in vitro expansion of human natural Treg was established to obtain large numbers of human Treg with highly suppressive phenotype and function, thereby providing a solution to the availability of sufficient human natural Treg in clinical study and immunotherapy.
Cell Culture Techniques ; Cell Separation ; Cells, Cultured ; Humans ; Interleukin-2 ; Leukocytes, Mononuclear ; Lymphocyte Culture Test, Mixed ; T-Lymphocytes, Regulatory ; cytology

Shexiang Baoxin pills （SBP） are prescribed based on Suhexiang Pills derived from the Formulary of the Bureau of Taiping People's Welfare Pharmacy （《太平惠民和剂局方》） in the Song Dynasty. As the classic Chinese patent medicine in warming and dredging with aromatics， SBP have been widely used in clinical treatment for 30 years by virtue of their unique efficacy in coronary atherosclerotic heart disease （CHD）. Angiogenesis is a biological process in which the body activates angiogenesis-related factors in the body to act on endothelial cells under local vascular injury， tumor growth， local inflammation， and other stimuli to promote the proliferation， migration， and infiltration of endothelial cells， and form new sprouting or non-sprouting blood vessels. As a new strategy for ischemic diseases such as CHD， therapeutic angiogenesis is of great significance in the prevention and treatment of CHD in promoting angiogenesis of ischemic myocardium and establishing effective collateral circulation. However， for the atherosclerotic plaque and tumor， angiogenesis promotion is a risk factor for accelerating the disease progression. Therefore， safe and effective regulation of ischemic myocardial angiogenesis has become the focus of the current prevention and treatment of CHD. Studies in recent years have shown that SBP can intervene in angiogenesis with multiple pathways and targets， which can exert therapeutic angiogenesis effect on CHD and also inhibit atherosclerotic plaque and tumor angiogenesis to varying degrees. This study reviewed the experimental and clinical trials on the regulatory effect of SBPs on angiogenesis in CHD to provide references for the research on Chinese medicine intervention in angiogenesis of CHD.

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

In recent years， coronary microvascular disease （CMVD）， a main type of ischemic heart disease with high incidence and low diagnosis rate， has become a new research hotspot and received much clinical attention. The etiology of CMVD is complex and the symptoms are various. Traditional Chinese and Western medicine have different opinions on its pathogenesis and treatment plan. Western medicine believes that CMVD is related to structural abnormalities （such as microvascular remodeling， vascular invasion， lumen obstruction， sparse vascular vessel and perivascular fibrosis） and functional abnormalities （such as endothelial dysfunction， smooth muscle cell dysfunction， microvascular constriction， microvascular spasm， inflammation and autonomic nervous dysfunction） of coronary microvascular vessels as well as the extravascular factors （such as heart rate and blood pressure）. In clinics， conventional western medicines are usually used for empirical treatment， but with undesirable effects. Traditional Chinese medicine （TCM） believes that CMVD belongs to the category of "chest impediment"， "heart pain" and "collateral disease"， and the common syndromes include Qi deficiency and blood stasis， Qi stagnation and blood stasis， Qi and Yin deficiency， congealing cold in heart vessel， heart and spleen deficiency， blood stasis obstructing collaterals， combined phlegm and blood stasis， and liver and kidney deficiency， with a variety of treatment methods. Specifically， Chinese patent medicines， self-designed prescriptions， modified classical prescriptions and TCM characteristic therapies have achieved certain effects. This review discussed the risk factors， pathological mechanism， TCM etiology and pathogenesis and traditional Chinese and Western medicine treatment of CMVD， to provide reference for the study and treatment of CMVD.

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg^-1）， and oseltamivir group （40 mg·kg^-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1^-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years. However, the quality control (QC) standards of SJZD are insufficient. Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formula rapidly. In this study, we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC. A total of 56 compounds in SJZD were characterized in vitro, and 23 compounds were discovered in vivo. A total of 58 biomarkers were related to SQDS, and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status. A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy. We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng; dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria; glycyrrhizic acid, isoglabrolide, and glycyrrhetnic acid as the q-markers of licorice; and 2-atractylenolide as the q-marker of macrocephala. According to the discovery of the SJZD q-markers, we can establish the quality standard that is related to efficacy.