Accumulating studies have proved that systemic inflammation is one of the important pathophysiologic mechanisms of heart failure. This article focuses on the sources of inflammation mediators and the causes of inflammation activation in heart failure including hemodynamic changes and oxidative stress, Toll-like receptors, microbial antigens and microorganisms, endotoxin hypothesis and neurohormonal activation. Furthermore, the effects of inflammation mediators such as cytokines and chemokines on heart failure are introduced. All lead to the conclusion that heart failure is a process with complex inflammation.

The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

Thirteen novel oleanolic acid (OA) derivatives were designed and synthesized with modification at positions of C-3, C-12 and C-28 of OA. Their structures were confirmed by MS, 1H NMR and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (SGC7901, MCF-7 and A549) were evaluated by MTT assay. The results indicated that the tested derivatives were found to have stronger cell growth inhibitory activity than OA. Among them, compounds II2 and II3 showed more potent cytotoxicity on MCF-7 and A549 tumor cells than gefitinib (positive control). They are worthy to be studied further.
Antineoplastic Agents, Phytogenic ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Drug Design ; Humans ; Oleanolic Acid ; chemical synthesis ; pharmacology

OBJECTIVETo study the effect of acupuncture on the immune function of sepsis patients.

METHODSNinety sepsis patients were assigned to the control group, the thymosin a1 group, and the acupuncture treatment group according to random digit table, 30 patients in each group. Patients in the control group were treated according to the guideline of Surviving Sepsis Campaign (SSC). Patients in the control group received routine treatment. Those in the thymosin alpha1 group additionally received subdermal injection of thymosin alpha1 (1.6 mg), once per day for 6 successive days. Needling at related points such as Zusanli (ST36), Yanglingquan (GB34), Neiguan (PC6), Guanyuan (RN4), and so on, was performed in patients of the acupuncture treatment group, once per day for 6 successive days. T cell subgroups (CD3+, CD4+, CD8+, CD4+ /CD8+) and immunoglobulin levels (IgG, IgA, IgM) were detected. The length of ICU hospital stay, hospital readmission rate, and 28-day mortality were compared among the three groups.

RESULTSAfter six days of treatment, CD3+, CD4+, CD8+, IgG, IgA, IgM, and CD4+ /CD8+ ratio of three groups were all significantly increased (P < 0.01). Of them, CD3+, CD4+, CD8+, IgG, IgA, and IgM increased more significantly in the thymosin alpha1 group and the acupuncture treatment group (P < 0.01). Compared with the control group, the ICU hospitalization length was significantly shortened, the hospital readmission rate and the 28-day mortality were lower in the thymosin alpha1 group and the acupuncture treatment group (P < 0.05, P < 0.01). There was no statistical difference in each index between the thymosin alpha1 group and the acupuncture treatment group (P > 0.05).

CONCLUSIONAcupuncture could adjust the immune function of sepsis patients, improve their immunological indicators and prognoses.

Acupuncture Therapy ; CD4-CD8 Ratio ; Humans ; Length of Stay ; Prognosis ; Sepsis ; diagnosis ; immunology ; therapy ; T-Lymphocyte Subsets ; Thymosin ; analogs & derivatives

Objective To report clinical manifestations, electroencephalogram (EEG), and the genotypes of two siblings with type Ⅲ Gaucher disease.Methods Two patients with different features were siblings. Their clinical data, signs, peripheral leukocytes acid β-glucosidase activity, andGBA gene were analyzed.Results (1) The proband was a boy. He visited us at the age of nine years old because of hepatosplenomegaly, thrombocytopenia and growth retardation without any neurologic symp-toms. He had normal intelligence but abnormal EEG ifndings. The activity of acid β-glucosidase in his leucocytes decreased to 1.5 nmol h-1·mg-1 Pr (normal range 6.0-16.7 nmol h-1·mg-1 Pr), supporting the diagnosis of type Ⅲ Gaucher disease. (2) The elder sister of the proband was 12 years old. She had tonic-clonic seizure and myoclonus seizure from the age of seven years old. Mild hepatomegaly, abnormal EEG, poor effect for antiepileptics, and progressive deterioration of psychomotor abilities were found. Her blood leucocytes acid β-glucosidase activity decreased to 1.8 nmol h-1·mg-1 Pr (normal range 6.0-16.7 nmol h-1·mg-1 Pr). Two heterozygous missense mutations, c.680A>G, (p.N188S) and c.1342G>C (p.D409H) were detected from the two siblings, respec-tively.Conclusions Patients with type Ⅲ Gaucher disease usually have the onset in childhood with typical features of Gaucher disease without neurologic involvement. Abnormal EEG may be helpful to the differential diagnosis of type I or type Ⅲ. On the other hand, neurologic manifestations could be presented as the ifrst symptom in some patients without viscera enlargement. The patients of type Ⅲ Gaucher disease with the same genotype could have different phenotypes, even between the siblings.

Objective To investigate the clinical feature and antibiotic resistance profile of K.pneumoniae isolates from patients for better management of K.pneumoniae infections.Methods Nonduplicate K.pneumoniae strains were collected from January to December in 2015.K.pneumoniae strains were identified by VITEK 2-Compact 60 and tested for antimicrobial susceptibility by KirbyBauer method.Results A total of 753 strains ofK.pneumoniae were included,most (40.9％,308/753) of which were isolated from sputum,followed by urine (18.2％,137/753).Most of the strains were from old patients at least 60 years of age (40.8％,307/753),and primarily from intensive care units (16.7％,126/753) and Department of Respiratory Medicine (13.7％,103/753).Respiratory tract infection was found in 144 patients,of which 71.5％ (103/144) were due to K.pneumoniae.More than half of the K.pneumoniae strains were resistant to piperacillin (66.3 ％),cefazolin (60.8 ％) and cefitroxime (59.4 ％).Only a few strain were resistant to imipenem (2.4 ％) and meropenem (2.0).ESBLs were produced in 410 (54.4 ％) of the 753 strains,and 29 (3.9 ％) strains were carbapenem-resistant,492 (65.3 ％) strains were resistant to multiple antimicrobial agents.Conclusions Clinical K.pneumoniae isolates are highly resistant to most of the antimicrobial agents tested.The strains were mostly isolated from sputum and urine,and positive for ESBLs.MDR K.pneumoniae sWains are emerging.K.pneumoniae isolates are still very susceptible to carbapenems in vitro.

OBJECTIVETo investigate the relationship between chronic pyelonephritis (CPN) and immune function, and the therapeutic mechanism of Yishenkang granule (YSKG).

METHODSOne hundred and twenty patients of CPN were divided into 3 groups randomly, the YSKG group (treated with YSKG), the control A group (treated with Sanjin tablet) and the control B group (treated with western medicine). Serum levels of immunoglobulin (Ig), complement 3 (C3), interleukin-2 (IL-2), peripheral T-lymphocyte subsets, and urinary secretory immunoglobulin A (sIgA) were determined before and after treatment with monoclonal antibody assay, agar diffusion method, radioimmunoassay (RIA), and radioimmuno-equilibrium method, and compared with normal control.

RESULTSThere were disorders of T-lymphocyte subsets in CPN, lowering of serum Ig, C3 and urinary sIgA, and increase of blood IL-2 (P < 0.05 or P < 0.01). These abnormalities could be normalized after YSKG treatment.

CONCLUSIONFunctional disorders of cellular and humoral immunity exist in CPN patients of chronic stage, YSKG could correct the immune functional disorder, control the recurrence of CPN effectively and alleviate the immunopathological damage.

Adult ; Chronic Disease ; Complement C3 ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Interleukin-2 ; blood ; Male ; Middle Aged ; Pyelonephritis ; drug therapy ; immunology ; prevention & control ; T-Lymphocyte Subsets ; drug effects

OBJECTIVETo observe the clinical effect of acupuncture on acute heart failure (AHF) patients.

METHODSTotally 60 patients who were diagnosed as AHF were assigned to the acupuncture group and the control group, 30 in each group. Those in the control group received inotropic agents, preload and afterload reducing therapy, anti-infection and so on. Besides, those in the acupuncture group received needling at relative points, once daily for 5 consecutive days. The mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), stroke volume index (SI), left ventricle working index (LCWI) were monitored by thermodilution pulse-indicated continuous cardiac output (PiCCO) technique. Changes of the aforesaid data were compared between before and after treatment. The ICU length of stay, readmission rate,and the 28-day mortality were also compared between the two groups.

RESULTSAfter 5 days of the treatment, CI, SI, and LCWI increased more obviously (P < 0.01), HR and MAP decreased significantly (P < 0.05). Of them, CI, SI, and LCWI increased more obviously in the acupuncture group (P < 0.05).There was no obvious difference in HR or MAP between the two groups (P > 0.05). Compared with the first day of admission in the same group, CI, SI, and LCWI obviously increased in the acupuncture group from the second day (P < 0.05). HR started to decrease since the fourth day (P < 0.05), and MAP began to decrease until the fifth day (P < 0.05). CI, SI, and LCWI started to increase in the control group from the third day (P < 0.05); HR and MAP both began to decrease since the fifth day (P < 0.05). Compared with the control group, the ICU length of stay was obviously shortened in the acupuncture group (P < 0.05). The readmission rate and the 28-day mortality rate were lower than those of the control group (P < 0.05).

CONCLUSIONThe combination of acupuncture and Western medical therapy might strengthen acute heart failure patients' heart functions, elevate the therapeutic effect, and improve the prognosis.

Acupuncture Therapy ; Adult ; Aged ; Aged, 80 and over ; Female ; Heart Failure ; physiopathology ; therapy ; Heart Rate ; Humans ; Male ; Middle Aged ; Stroke Volume

Objective To investigate the impact of aging and vascular endothelial function on arterial stiff- ness in patients with isolated systolic hypertension.Methods Patients with isolated systolic hypertension (ISH,n=75)age-matched healthy subjects(n=30)and young healthy subjects(n=50)were submitted to deter- mination of aortic pulse wave velocity(baPWV)and vascular endothelial function evaluated by flow-mediated dila- tion(FMD).Results baPWV was progresively decreased(ISH:2459.2?436.8 vs elderly healthy:2097.2? 315.7 vs young healthy:1619.7?214.2 cm/s,P

OBJECTIVETo investigate the expression of angiotensin converting enzyme (ACE) and ACE2 Gene in lung of paraquat poisoning rats and the protection of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODSOne hundred SD male rats were randomly equally divided into 4 groups:normal control group (10 rats), drug control group (40 rats), paraquat poisoning group (40 rats) and drug intervention group(40 rats). The paraquat poisoning and drug intervention group rats were injected intraperitoneally by paraquat (20 mg/kg). The rats in drug intervention group rats were protected by intraperitoneal injection with Na-DMPS (200 mg/kg) 15 min before exposure of paraquat. Behavioral changes of the rats and histological changes of lung tissues under light microscope were observed. And the expression of ACE and ACE2 mRNA in lung tissues of rats both in paraquat poisoned group and drug intervention group were measured by RT-PCR at different time of 6 h, 24 h, 3 and 7 d after poisoning.

RESULTSThe poisoning symptoms of shortness of breath, cramps appeared and deteriorated progressively in rats after paraquat exposure and the protection of NA-DMPS could delay and reduce these symptoms significantly. Histological appearance of disorganization of pulmonary capillary and alveolus, exudation in alveolar space, pulmonary edema, severe bleeding, and inflammatory cells infiltration were obvious in lungs of rats after paraquat poisoning, whereas the histological changes were extenuated by protection of NA-DMPS. As compared with normal control group (NC group), the expressions of ACE, ACE2 mRNA in lung tissue decreased, and the lowest level of ACE mRNA expressions appeared at 24 h (0.457 +/- 0.262), on 3 d (0.385 +/- 0.179) after Paraquat exposure (P < 0.05), while lowest level of ACE2 mRNA expressions appeared on 3 d (0.415 +/- 0.247), 7 d (0.365 +/- 0.215) (P < 0.05). As compared with paraquat poisoned group, the expressions of ACE mRNA in lung tissue of rats in NA-DMPS protected group increased significantly at 24 h (0.739 +/- 0.558) and 3 d (0.749 +/- 0.414) (P < 0.05), while the expressions of ACE2 mRNA increased markedly on 3 d (0.584 +/- 0.345) and 7 d (0.493 +/- 0.292) (P < 0.05). But the expression of ACEmRNA and ACE2 mRNA in lungs had no statistical significance between normal control group and drug intervention group (P > 0.05).

CONCLUSIONThe expressions of ACE and ACE2 mRNA in lung tissue of the rats with paraquat poisoning are decreased. Na-DMPS can effectively improve the balance of RAS in local lung tissue and reduce the pathological changes of lung tissue, delay the poisoning symptoms and show protective effects for acute lung injury induced by paraquat.

Animals ; Lung ; drug effects ; enzymology ; Male ; Paraquat ; poisoning ; Peptidyl-Dipeptidase A ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Unithiol ; pharmacology