Immune cells are formed by the proliferation and differentiation of hematopoietic stem cells in the bone marrow,in-cluding lymphocytes,macrophages,etc,which participate in the immune defense,immune stability and immune monitoring of the body,and are an indispensable basic component of the immune system.Basic helix-loop-helix family member E40(BHLHE40)has been shown to play an important role in adipogenesis,tumorigenesis,circadian rhythm and hypoxia response.Recently,it was found that BHLHE40 plays a key role in the cell cycle,proliferation and cytokine production of immune cells.This article will review the discovery,naming,structure,and mechanism of BHLHE40 in various periods,as well as it's research progress in immune cells,in order to provide new target for the treatment of immune-related diseases at the genetic level.

Immune disorders play a vital role in the tumors,infections and allergic diseases.As a co-inhibitory molecule that has attracted much attention in recent years,programmed cell death protein 1(PD-1)can participate in immunomodulation in various immune diseases by inhibiting the proliferation and activation of type 2 innate lymphoid cells(ILC2s).ILC2s is a newly discovered subgroup of immune cell families,which is involved in tumor immunity,anti-parasitic infection and tissue damage repair by secreting type 2 cytokines.PD-1 is a major immunosuppressive molecule that can regulate the different immunomodulatory effects of ILC2s in different immune diseases.This article reviews the role and mechanism of PD-1 in regulating ILC2s in different diseases.

Immune cells are formed by the proliferation and differentiation of hematopoietic stem cells in the bone marrow,in-cluding lymphocytes,macrophages,etc,which participate in the immune defense,immune stability and immune monitoring of the body,and are an indispensable basic component of the immune system.Basic helix-loop-helix family member E40(BHLHE40)has been shown to play an important role in adipogenesis,tumorigenesis,circadian rhythm and hypoxia response.Recently,it was found that BHLHE40 plays a key role in the cell cycle,proliferation and cytokine production of immune cells.This article will review the discovery,naming,structure,and mechanism of BHLHE40 in various periods,as well as it's research progress in immune cells,in order to provide new target for the treatment of immune-related diseases at the genetic level.

Immune disorders play a vital role in the tumors,infections and allergic diseases.As a co-inhibitory molecule that has attracted much attention in recent years,programmed cell death protein 1(PD-1)can participate in immunomodulation in various immune diseases by inhibiting the proliferation and activation of type 2 innate lymphoid cells(ILC2s).ILC2s is a newly discovered subgroup of immune cell families,which is involved in tumor immunity,anti-parasitic infection and tissue damage repair by secreting type 2 cytokines.PD-1 is a major immunosuppressive molecule that can regulate the different immunomodulatory effects of ILC2s in different immune diseases.This article reviews the role and mechanism of PD-1 in regulating ILC2s in different diseases.

OBJECTIVE To clarify the components of volatile oil in branches and leaves of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii. METHODS The total volatile oil in leaves and branches of these plants were obtained by supercritical CO2 extraction. After that, the chemical composition of the total volatile oil was analyzed and identified by GC-MS, and the contents of different parts and varieties were compared. RESULTS The results showed that the highest oil yield of leaves was Rhododendron thymifolium(6.97%), and the highest oil yield of branches was Rhododendron anthopogonoides(20.53%). Thirty-five, eighty, fifty-eight and forty compounds were detected in the branch oil of Rhododendron anthopogonoides, Rhododendron capitatum, Rhododendron thymifolium and Rhododendron przewalskii respectively, among which Rhododendron capitatum was rich in compounds. Forty-eight, fifty-seven, sixty-two and fifty compounds were detected in the leaf oil, among which the compounds of Rhododendron anthopogonoides were the richest. Among the detected components, squalene(34.92%, 26.90%) was the highest content in the branches and leaves of Rhododendron anthopogonoides. 1-Eicosanol(26.79%) was the highest content in the branch oil of Rhododendron capitatum, and octadecyl acetate(42.32%) was the highest content in the leaf oil. The highest content of bisabola-3,10-diene-2-one(34.66%, 28.20%) was found in the branches and leaves of Rhododendron thymifolium, and 15-oxoETE(38.20%, 40.40%) was the highest content in the branches and leaves of Rhododendron przewalskii. The results showed that the contents of oil in branches and leaves of Rhododendron capitatum were quite different in different parts. In the comparison of different varieties, the compounds with the highest content of four rhododendrons were all different. CONCLUSION According to the difference of the content of active components of different rhododendrons and parts, the appropriate species and parts for purposeful development and utilization should be selected. The research results can provide scientific basis for rational development and utilization of Rhododendron resources.

Objective:To explore the effect and safety of stereotactic aspiration of necrotic brain tissue for the patients≥61 years with malignant middle cerebral artery infarction (MMI).Methods:A total of 102 MMI patients aged≥61 years were enrolled retrospectively. All patients were subject to conservative medical treatment alone or in addition to stereotactic aspiration of necrotic brain tissue 24-72 hours after symptom onset. Perioperative outcomes and 6-month follow-up outcomes were observed and evaluated.Results:Baseline data characteristics were well balanced between the conservative treat group and aspiration group, except for the prevalence of hypertension. The incidence of early cerebral herniation (9.1% vs. 48.3%, χ2=17.843, P<0.001) and death (13.6% vs. 60.3%, χ2=22.707, P<0.001)in the aspiration group was significantly lower than that in the conservative group, and there was no significant difference in the incidence of cerebral hemorrhage ( P=0.726) and intracranial infection ( P=0.186) between the groups. At 6-month follow-up, compared with the conservative treatment group, the aspiration group had a higher proportion of favorable outcome (mRS 0-3) (38.6% vs. 3.4%, χ2 =20.438, P<0.001) and survival without severe disability (mRS 0-4) (68.2% vs. 22.4%, χ2=21.492, P<0.001). Comparison of clinical characteristics of favorable outcome (mRS 0-3) group and unfavorable (mRS 4-6) group showed that the proportion of patients treated with aspiration was significantly higher than that treated with medical therapy alone (89.5% vs. 10.5%, P<0.001). Multivariate logisitic regression used to adjust the confound factors such as atrial fibrillation, diabetes and smoking, the GCS and the NIHSS score of 24 hours after onset, etc, revealed that the treatment with aspiration was an independent association factor for the ratio of 6-month favorable outcome for the elderly patients with MMI ( OR=126.704, 95% CI: 7.236-2218.610, P<0.001). Conclusions:The stereotactic aspiration of necrotic brain tissue are effective and safe for the elderly patients with MMI.

BACKGROUND: Since the diagnostic value of aldosterone to renin ratio (ARR) calculated by plasma renin concentration (PRC) or plasma renin activity (PRA) is still inconclusive, we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA, so as to provide guidance for clinical diagnosis. METHODS: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to March 2021. We included studies that report the true positive, false positive, true negative, and false negative values for the diagnosis of primary aldosteronism, and we excluded duplicate publications, research without full text, incomplete information, or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. RESULTS: The pooled results showed that ARR (plasma aldosterone concentration [PAC]/PRC) had a sensitivity of 0.82 (95% confidence interval [CI]: 0.78-0.86), a specificity of 0.94 (95% CI: 0.92-0.95), a positive-likelihood ratio (LR) of 12.77 (95% CI: 7.04-23.73), a negative LR of 0.11 (95% CI: 0.07-0.17), and symmetric area under the curve (SAUC) of 0.982, respectively. Furthermore, the diagnostic odds ratio (DOR) of ARR (PAC/PRC) was 180.21. Additionally, the pooled results showed that ARR (PAC/PRA) had a sensitivity of 0.91 (95% CI: 0.86-0.95), a specificity of 0.91 (95% CI: 0.90-0.93), a positive LR of 7.30 (95% CI: 2.99-17.99), a negative LR of 0.10 (95% CI: 0.04-0.26), and SAUC of 0.976, respectively. The DOR of ARR (PAC/PRA) was 155.52. Additionally, we conducted a subgroup analysis for the different thresholds (<35 or ≥35) of PAC/PRC. The results showed that the DOR of the cut-off ≥35 groups was higher than the cut-off <35 groups (DOR = 340.15, 95% CI: 38.32-3019.66; DOR = 116.40, 95% CI = 23.28-581.92). CONCLUSIONS The research results suggest that the determination of ARR (PAC/PRC) and ARR (PAC/PRA) was all effective screening tools for PA. The diagnostic accuracy and diagnostic value of ARR (PAC/PRC) are higher than ARR (PAC/PRA). In addition, within a certain range, the higher the threshold, the better the diagnostic value.
Aldosterone ; Area Under Curve ; Humans ; Hyperaldosteronism/diagnosis* ; Hypertension ; Renin

Objective:The aims of this study were to compare the efficacy between salvage liver transplantation (sLT) and rehepatectomy (RR) basing on the propensity score matching (PSM), and to explore the prognositc factors of patients with recurrent hepatocellular carcinoma (HCC).Methods:124 patients with intrahepatic recurrence after hepatectomy in our center from January 2012 to August 2018 were divided into sLT group( n=46) and RR group( n=78). 34 patients were selected for data analysis base on 1∶1 propensity score matching (PSM). The advantages and disadvantages of the two surgical methods and the prognostic factors of the patients were discussed by comparing the basic clinical data, OS and DFS of the two groups before and after matching. Results:Before matching, the pre-operative serum total bilirubin, the occurrence of multiple tumors, the proportion of preoperative TACE and the proportion of patients within Milan criteria of the sLT group were higher than those of the RR group, and the maximum tumor diameter of the sLT group was shorter than that of the RR group ( P<0.05); the time of operation, the amount of intra-operative blood loss, the positive of MVI and the proportion of postoperative Clavien grade Ⅲ and above of RR group were higher than those of RR group ( P<0.05). After matching, the operation time, intra-operative blood loss and the proportion of postoperative complications of sLT group were higher than those of RR group; there was nosignificant difference between 1-, 3- and 5- years OS of sLT group and RR group( P>0.05), the 1-, 3- and 5-years DFS of sLT group were better than those of RR group( P<0.05); AFP≥100 μg/L was the independent risk factor of OS, and the type of operation and AFP≥100 μg/L were independent risk factors of DFS. Conclusions:The pre-operative condition of sLT group was more severe, and the operation time, intra-operative blood loss and post-operative severe complication rate of sLT group were higher than those of RR group, and the DFS time of sLT group was longer than that of RR group, but there was no significant difference in OS between the two groups.

To investigate the effect of glycyrrhizinate and phospholipids (DGPL) complex on inflammatory gene expression in cell inflammation model induced by palmitic acid (PA).Huh7 cells were divided into control, PA and PA+DGPL groups. For control group, cells were treated with BSA; for PA group, cells were incubated with 0.2 mmol/L saturated fatty acid PA, PA+DGPL group was given 20 μmol/L or 100 μmol/L DGPL in addition to 0.2 μmol/L PA. After 24 h, the expression of inflammation-related genes COX-2 and iNOS and endoplasmic reticulum (ER) stress-related gene GRP78 was determined by RT PCR. Oil red staining was conducted to observe the effect of DGLP on steatosis.Compared with control group, the expression of COX-2, iNOS and GRP78 in PA group was enhanced to 6.07±0.73(<0.05), 3.18±0.91 (<0.01) and 3.21±1.00(<0.05), respectively. Compared to control group, the expression of COX-2,iNOS and GRP78 in 100 μmol/L DGPL group was reduced to 2.40±0.76, 1.60±0.49 and 1.17 ±0.42 (<0.05); and 20 μmol DGPL had similar inhibition effect on COX-2 and iNOS elevation induced by PA (<0.01,<0.05 respectively). In addition, DGLP enhances the steatosis of Huh7 cells as demonstrated by oil red staining.PA can induce the up-regulated expression of inflammation associated genes COX-2, iNOS and ER stress-associated gene GRP78 in Huh7 cells. DGPL is able to protect Huh7 cells from PA induced inflammatory gene expression and the beneficial effect may be partially due to its unsaturated phospholipid component, which may improve ER stress and enhance steatosis.

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.