Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.
Mice ; Animals ; Heart Failure/metabolism* ; Stroke Volume ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Metabolomics ; Arachidonic Acids ; Proline

2019-nCoV Omicron (B.1.1.529) variant, which has brought new challenges to the prevention and control of COVID-19 pandemic, has the characteristics of stronger transmissibility and more rapid transmission and more significant immune evasion. It took only two months to become a predominant strain worldwide after its identification in South Africa in November 2021. Local epidemics caused by Omicron variant have been reported in several provinces in China. However, the epidemiological characteristics of highly mutated Omicron variant remain unclear. This article summarizes the progress in the research of functional mutations, transmissibility, virulence, immune evasion and cross-reactive immune responses of Omicron variant, to provide references for the effective prevention and control of COVID-19 pandemic caused by Omicron variant.
COVID-19 ; Humans ; Mutation ; Pandemics ; SARS-CoV-2

Molecular pharmacognosy( MP) is a new interdisciplinary science,which integrates the pharmacognosy and molecular biology,and focuses on the crude drugs' classification and identification,cultivation and protection,and production of active ingredients at the molecular level. Pogostemon cablin is one of the ten major southern medicines in China,MP research on this famous herb has developed on the basis of traditional research methods,and achieved certain results. This article summarized the MP research achievements of P. cablin in recent years,the prospect of this field is also discussed to provide references for the protection,development and utilization of P. cablin resources.
China ; Lamiaceae ; Molecular Biology ; Pharmacognosy ; Pogostemon

OBJECTIVETo study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).

METHODSPBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.

RESULTSExposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).

CONCLUSIONHBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.

Adult ; Case-Control Studies ; Cells, Cultured ; Female ; Hepatitis B e Antigens ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Interferon-gamma ; immunology ; Interleukin-10 ; immunology ; Interleukin-6 ; immunology ; Leukocytes, Mononuclear ; immunology ; metabolism ; Male ; Middle Aged ; Recombinant Proteins ; immunology ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology

This report aims to investigate the dynamical changes of HBcAg18-27 epitope specific cytotoxic T lymphocytes(CTL), alanine aminotransferase (ALT), HBV DNA and HBsAg in peripheral blood of acute hepatitis B patients, and to explore the roles of HBcAg18-27-specific CTLs in virus clearance and liver injury. Acute hepatitis B (AHB) and chronic hepatitis B (CHB) patients were divided into two groups according to results of HLA-A0201. Patients with positive HLA-A0201 were classified into HBcAg-specific CTL group and those with negative HLA-A0201 were referred as control group. The specific CTLs were stained with HLA-A0201 limited HBcAg18-27 epitope MHC-Pentamer and the frequencies of CTLs, T, B, NK and NKT cells were detected by flow cytometry (FCM). The serum ALT, HBV DNA and HBsAg were examined using speed analysis, quantitative PCR and abbott chemiluminescent technology. The frequencies of HBcAg18-27-specific CTLs in AHB patients were higher in the early three weeks as compared to the late three weeks. The apex time of HBV-specific CTL frequencies lagged behind those of HBV DNA, HBsAg and ALT. The loss of HBsAg in patients with high frequencies of HBV-specific CTL was earlier than that in patients with low frequencies (t = 2.018, P value is less than 0.05). In the second week the peak frequencies of CD3+CD8+ cells overlapped with that of HBcAg18-27-specific CTLs and with a positive correlation between (r = 0.420, P value is less than 0.05). During the early stages of AHB, the frequencies of NK and NKT cells were found significantly lower than that of control group and CHB group and the levels were back to normal after recovery. Moreover, a negative correlation existed between the frequencies of NK cells and the dynamic changes of HBcAg18-27-specific CTLs (r = -0.435, P value is less than 0.01) in AHB group. The frequencies of HBcAg18-27-specific CTLs were significantly higher as compared to CHB group in the first three weeks (z = -3.258, -4.04, and -3.259, P value is less than 0.01). The early loss of HBsAg was closely related to the high frequencies of HBcAg18-27 specific CTLs in AHB patients. HBcAg-specific CTL frequencies in peripheral blood could be used to predict clinical outcome after HBV infection. The frequencies of CD8+ T cells can reflect the changes of frequencies of HBcAg-specific CTL during acute HBV infection.
Adolescent ; Adult ; Case-Control Studies ; Female ; HLA-A2 Antigen ; immunology ; Hepatitis B ; immunology ; Hepatitis B Core Antigens ; blood ; immunology ; Humans ; Killer Cells, Natural ; immunology ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; Young Adult

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Cell Line, Tumor ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; Proto-Oncogene Proteins ; metabolism

OBJECTIVETo investigate the clinical manifestations and endoscopic features of abdominal type Henoch purpura in children and improve the diagnostic level.

METHODSRetrospective review was made on the clinical, endoscopic and histopathological features of 57 cases of children with Henoch purpura abdominal type who had been hospitalized from Jan. 2002 to May 2007. Upper gastrointestinal endoscopy was performed in all cases. All the cases had various digestive system symptoms without cutaneous purpura before endoscopy. Mucosal specimens were taken from sinus ventriculi and duodenum for histopathological analysis. Helicobacter pylori (H.pylori) infection was identified by rapid urease test and histology, and diagnosis of H.pylori infection was made when both were positive.

RESULTSThe common gastrointestinal symptoms of Henoch purpura were abdominal pain (46 cases), vomiting (32 cases), hematochezia (11 cases), diarrhea (4 cases) and abdominal distention (1 case). Three cases had arthralgia and joint swelling. The main laboratory findings were increased peripheral white blood cells (33 cases, 57.9%), 1/5 of cases had elevated C reactive protein (CRP), low serum albumin and seroperitoneum. Endoscopy demonstrated the damages to the mucosa, which varied from congestion, edema, petechia and ecchymosis (37 cases, 64.9%) to erosive and multiple ulcers (14 cases, 24.6%), granulation of mucosa in descendent duodenum (4 cases, 7.0%), and diffuse hemorrhage of mucosa (2 cases, 3.5%). The upper gastrointestinal endoscopy showed that the commonest and most serious position involved was the descendent duodenum (55 cases, 96.5%), followed by duodenal bulb (32 cases, 56.1%) and stomach (18 cases, 36.1%), esophagus was less involved (1 case, 1.8%). Histological manifestations showed swollen vascular endothelial cells of capillary vessels and small blood vessels, fibrotic necrosis of small vessels and bleeding, diffuse perivascular lymphocytic and neutrophilic infiltration and nuclear debris in mucosa and submucosa. Three cases (5.3%) were found infected with H. pylori. In 49 cases (86.0%) cutaneous purpura appeared 1 - 7 days after endoscopy. Eight cases had no cutaneous purpura until they left hospital. Two cases were lost to follow up and 6 cases (10.5%) remained free from cutaneous purpura were followed up until now (1 - 5 years).

CONCLUSIONDescending duodenum is the commonest and most serious position of upper gastrointestinal tract involved in Henoch purpura. Upper gastrointestinal endoscopy with the mucosal biopsy are useful for the early diagnosis of Henoch purpura.

Abdominal Pain ; pathology ; physiopathology ; Child ; Duodenum ; pathology ; physiopathology ; Endoscopy ; instrumentation ; Humans ; Purpura, Schoenlein-Henoch ; pathology ; physiopathology

OBJECTIVE: To explore the role of combined heart-thymus transplantation for heart allograft in rats. METHODS: Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, infiltration of CD4+, CD8+ T cells, level and mRNA expressions of IL-2 and IL-4 in the serum and cardiac grafts were investigated. RESULTS: Heart allograft in the controls had a survival time of (6.0+/-0.76) d. heart-thymus combined transplantation in non-thymectomized rats had a survival time of (6.88+/-0.64)d (P<0.05). Heart-thymus combined transplantation in thymectomized rats led to an evident survival time of (14.13+/-5.82)d (P<0.01) for cardiac graft, which further obtained long term survival after short course of treatment with cyclosporine. Pathologic lesion and infiltration of CD4+ and CD8+ T cells in cardiac grafts showed mitigated in the long term survival group. IL-2 level in the serum and cardiac grafts maintained low level in the long term survival group, whereas IL-4 maintained high level. CONCLUSION Whether thymectomized or not in recipient rats, heart-thymus combined transplantation has a positive effect to protect cardiac graft. Furthermore, in thymectomized rats heart-thymus combined transplantation may lead to evident survival prolongation of the heart grafts, which induces immune tolerance in short course of treatment with cyclosporine.
Animals ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Cyclosporine ; therapeutic use ; Graft Survival ; drug effects ; immunology ; Heart Transplantation ; Immune Tolerance ; drug effects ; immunology ; Immunosuppressive Agents ; therapeutic use ; Interleukin-2 ; blood ; genetics ; Interleukin-4 ; blood ; genetics ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Thymectomy ; Thymus Gland ; transplantation ; Time Factors ; Transplantation Immunology ; immunology ; Transplantation, Homologous

OBJECTIVE: To observe the effect of FTY720 and ICAM-1 mAb mono and combination therapy in mouse-to-rat cardiac xenotransplantation. METHODS: Cardiac xenotransplantation was performed in abdominal site with micro-surgical technique. Recipients with xenografts were treated with different doses of FTY720 and/or ICAM-1 mAb. Graft survival, histopathology, infiltration of CD4+, and CD8+ T cells and levels of serum IL-2, IFN-gamma, IL-4, and IgM were investigated. RESULTS: Survival time of xenografts was (2.75+/- 0.43)d in the controls, survival of grafts treated with ICAM-1 mAb did not significantly improve. Treatment with large dose FTY720 led to a survival of (4.25+/- 0.71)d (P<0.01). Combination therapy with large dose FTY720 and ICAM-1 mAb achieved a significant prolongation of graft survival with (10.25+/- 2.12)d (P<0.01). Levels of serum IL-2, IFN-gamma and rat-anti-mouse IgM decreased in the combined therapy group. Pathologic lesion and infiltration of T cells in xenografts showed mitigated in the large dose combined therapy group. There was a significant negative correlation between the antibody level and the graft survival time (R=-0.754, P<0.01). CONCLUSION The combined therapy of FTY720 and ICAM-1 mAb can achieve a significant effect in the prolongation of heart xenograft survival and inhibition of xenoantibodies.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Fingolimod Hydrochloride ; Graft Rejection ; blood ; etiology ; prevention & control ; Graft Survival ; drug effects ; Heart Transplantation ; adverse effects ; methods ; Immunoglobulin M ; blood ; Immunosuppressive Agents ; therapeutic use ; Intercellular Adhesion Molecule-1 ; immunology ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Mice ; Mice, Inbred BALB C ; Propylene Glycols ; therapeutic use ; Rats ; Rats, Wistar ; Sphingosine ; analogs & derivatives ; therapeutic use ; Time Factors ; Transplantation, Heterologous

OBJECTIVE: To explore the role of allo heart and thymus transplantation by intrathymic inoculation of thymocytes. METHODS: Wistar recipients were given intrathymic injection of allo thymocytes (2 x 10(7)) 14 days before the heart and/or thymus transplantation. Graft survival, histopathology, levels and mRNA expressions of IL-2, IL-4 in serum and cardiac-grafts were investigated. RESULTS: Heart transplantation and heart-thymus composite transplantation with the treatment of CysA for 7 or 14 days prolonged graft survival. Heart transplantation and heart-thymus composite transplantation with intrathymic thymocytes injection induced the long-term survival of allo-grafts transiently immunosuppressed with CysA; IL-4 maintained at high levels but IL-2 kept at low levels in grafts in long-term survivals. CONCLUSION Intrathymic inoculation of allo thymoctyes can induce immune tolerance for both cardiac transplantation and heart-thymus combined transplantation in rats. Thymus graft may play a role in the induction and maintenance of central tolerance.
Animals ; Cell Transplantation ; Female ; Graft Rejection ; prevention & control ; Graft Survival ; Heart Transplantation ; Immune Tolerance ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Thymus Gland ; cytology ; transplantation