Heme oxygenase-1 (HO-1) plays important roles in anti-oxidant, anti-inflammatory and immunoregulative activities. The aim of this study was to observe if HO-1 transfection could inhibit the damage of osteoblasts induced by ethanol. HO-1 was transfected into osteoblasts via constructed plasmid. After exposure to ethanol for 24 h, cytoactivity and apoptosis of osteoblasts were measured by MTT assay and flow cytometry, respectively. Furthermore, the oxidative stress and inflammatory factors in osteoblasts were measured. Compared to positive control group, the cytoactivity of transfected osteoblasts was significantly increased, and the apoptosis rate was significantly decreased (P<0.05). At the same time, the levels of reactive oxygen species (ROS), methane dicarboxylic aldehyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were significantly decreased (P<0.05), and superoxide dismutase (SOD) level was increased (P<0.05) in the transfected osteoblasts as compared with positive controls. These results suggest that HO-1 plays a protective role in osteoblasts, and HO-1 transfection can effectively inhibit bone damage induced by ethanol.
Cells, Cultured ; Ethanol ; toxicity ; Gene Expression Regulation ; drug effects ; Genetic Vectors ; pharmacology ; Heme Oxygenase-1 ; genetics ; metabolism ; Humans ; Osteoblasts ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Transfection

Aged ; Central Nervous System Neoplasms ; pathology ; Humans ; Lymphoma, Non-Hodgkin ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged

Objective To investigate the associations between soluble growth stimulation expressed gene 2 protein(sST2),conventional biomarkers and left ventricular geometry in patients with chronic kidney disease(CKD).Methods Patients with non-dialysis-dependent CKD in Department of Nephrology,Zhongshan Hospital,Fudan University were enrolled from August 2019 to December 2020.Clinical data were collected,and serum sST2,N-terminal pro-B-type natriuretic peptide(NT-proBNP)and high-sensitivity cardiac troponin T(hs-cTnT)were measured.Left ventricular structure was assessed by transthoracic echocardiography.Left ventricular geometric patterns were defined according to left ventricular mass index(LVMI)and relative wall thickness(RWT).Differences of cardiac biomarkers between different left ventricle geometric groups were analyzed with Tukey's post-hoc test.Multiple linear regression models were used to evaluate the correlations between biomarkers and cardiac structure parameters.Results A total of 652 patients with CKD were enrolled,and the detection rate of LVH was 33.4%.The detection rate of LVH increased as kidney function worsened,with 64.3%in CKD G5 patients.Compared with normal geometry group,NT-proBNP and hs-cTnT levels elevated in both concentric LVH(cLVH)and eccentric LVH(eLVH)patients(P＜0.001),while sST2 level only elevated in the cLVH patients(P=0.025).Multiple linear regression analysis showed that sST2 was associated with LAD and LVMI(P＜0.01);NT-proBNP was associated with left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),posterior wall thickness(PWT),interventricular septum thickness(IVST),left ventricular ejection fraction(LVEF),left ventricular mass(LVM),and LVMI(P＜0.000 1);hs-cTnT was associated with LAD,PWT,IVST,LVM,RWT and LVMI(P＜0.01).Conclusions sST2 could increase in CKD patients with cLVH,while has not significant change in eLVH patients,which is different from NT-proBNP and hs-cTnT.

Objective:To evaluate the influence of cytomegalovirus (CMV) infection on T cell senescence and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:It was a single center cross sectional study. Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay. CD28 - T cell was evaluated by flow cytometry. Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups. Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28 - T cell compartment. Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD. Results:A total of 438 MHD patients (270 men and 168 women) were enrolled in the study. The median age was 62 (51, 70) years. The median time on hemodialysis was 57 (21, 100) months. The primary diseases included chronic glomerulonephritis [213 cases (48.6%)], diabetic nephropathy [82 cases (18.7%)], polycystic kidney disease [34 cases (7.8%)], hypertensive renal disease [34 cases (7.8%)], etc. Of these patients, 430 (98.2%) were seropositive for anti-CMV-IgG, 206 (47.0%) had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml. Patients aged over 70 years old were 100% seropositive for anti-CMV-IgG. Patients on HD for more than 5 years had a higher seropositive rate of 99.1% than those with shorter HD duration, although these results were not statistically significant. Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4 + CD28 - T cells and CD8 + CD28 - T cells ( r=0.316, P<0.001; r=0.272, P<0.001). Multiple linear regression analysis showed that after adjusting for age and gender, lg[CD4 + CD28 - T cells(%)] and lg[CD8 + CD28 - T cells(%)] were positively correlated with lg[anti-CMV-IgG titers (U/ml)], respectively ( β=0.455, t=8.315, P<0.001; β=0.412, t=7.282, P<0.001). In analyzing the relationship between anti-CMV-IgG titers and CVD, patients were divided into six groups according to age and anti-CMV-IgG level. Group 1 included young patients with a lower anti-CMV-IgG titers (age ≤55 years old, anti-CMV-IgG <400 U/ml); Group 2 included young patients with a higher anti-CMV-IgG titers (age≤55 years old, anti-CMV-IgG ≥400 U/ml); Group 3 included middle-aged patients with a lower anti-CMV-IgG titers (5565 years old, anti-CMV-IgG<400 U/ml); Group 6 included old aged patients with a higher anti-CMV-IgG titers (age>65 years old, anti-CMV-IgG≥400 U/ml). The incidence of CVD was significantly different among the six groups ( χ2=18.780, P=0.002) and patients aged over 55 years old with higher anti-CMV-IgG level had a higher CVD incidence compared with group 1 ( P<0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.020, 95% CI 1.002-1.038, P=0.033), male ( OR=1.855, 95% CI 1.161-2.965, P=0.010), history of diabetes ( OR=1.867, 95% CI 1.145-3.046, P=0.012), increased lg[NT-proBNP(μg/L)] ( OR=2.848, 95% CI 1.816-4.467, P<0.001) and lg[anti-CMV-IgG (U/ml)] ( OR=3.183, 95% CI 1.582- 6.405, P=0.001) were independent factors associated with CVD in MHD patients. Conclusions:CMV infection is extremely common in MHD patients. Increased anti-CMV-IgG is related to T cell senescence and CVD complications in MHD patients.

Objective To explore the intervention effect and mechanism of sitagliptin on renal injury in type 1 diabetic (T1DM) mice.Methods The modeling group was intraperitoneally injected with streptozotocin (150 mg· kg-1) once and blood glucose ≥ 16.7 mmol · L-1 was considered as diabetes mellitus (DM).DM mice were randomly divided into two groups:model group and experimental group.Experimental group was treated with sitagliptin (15 mg · kg-1 · d-1) via intragastric administration for 4 weeks while the mice in model group and normal group treated with equal volume of ultrapure water.The 24 h microalbuminuria(ALB) was determined after administration.At the end of the experiment,urea nitrogen (BUN) and creatinine (SCr) in serum was detected.The protein expression levels of transforming growth factor-β1 (TGF-β1),Smad2,Smad3 were measured by Western blot.Results After administration sitagliptin for 4 weeks,the contents of ALB in model group and experimental group were (11.96 ± 3.36) (2.46 ±0.97) mg/24 h with significantly(P ＜0.001).The index of kidney weight/body weight(KW/BW) in normal group,model group and experimental group were 15.20 ±2.24,21.43 ±2.16,15.14 ±4.14;compared with normal group,the difference was significantly increased (P ＜ 0.05);compared with model group,the difference was significantly increased (P ＜0.05).The SCr in model group and experimental group were (352.58 ±47.09),(238.51 ± 53.03) μmol · L-1;the BUN in the two groups were(26.08 ±4.65),(10.40 ±2.47)mmol · L-1;compared with model group,the difference was significantly increased (P ＜0.01,P ＜0.001).The expression levels of TGF-β1,Smad2/3 and p-Smad2/3 in normal group,model group and experimental group were 0.19 ±0.02,0.12 ±0.02,0.07 ±0.01;0.23 ±0.02,0.27 ±0.04,0.13 ±0.01;0.18 ±0.01,0.14 ±0.01,0.11 ±0.00,compared with normal group,the difference was significantly increased (P＜0.05,P＜0.01);compared with model group,the difference was significantly increased (P ＜0.05,P ＜0.01).Conclusion Experimental delaying the progression of T1DM nephropathy without not decreasing blood glucose can effect partly through inhibiting TGF-β1/Smad2/3 pathway.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

This experiment focused on the effect of salvianolic acid B's nasal absorption characteristics in rats. In the study, HPLC determination of salvianolic acid B(SalB) in perfusion liquid was established to examine the SalB nasal irritation in different pH buffers and stability in nasal perfusion solution, and systematically study in vivo nasal absorption characteristics of SalB. Improved rats were adopted to establish the in situ nasal perfusion model to measure the release of total protein and lactate dehydrogenase in perfusion fluid, quantitatively evaluate the nasal irritation and the stability in perfusion liquid of pH 4.0, 5.0, 6.0 SalB phosphate buffer, compare the absorption of SalB in pH 5.0 buffer solution with low, medium and high concentrations (200, 400, 800 mg•L⁻¹). According to the results, nasal irritation: pH 4.0>pH 5.0>pH 6.0, RSD of pH 6.0 SalB buffer solution within 24 h was 3.1%, stability was poor. PH 5.0 SalB buffer solution had a smaller irritation and good stability. According to the nose perfusion test in rats, the nasal absorption of SalB fitted the first-order process and could be considered as passive absorption based on concentration gradient. SalB buffer solution of pH 5.0 had also a small nasal irritation and good stability, with a good absorption in rat nasal perfusion test, which therefore had a certain significance for the development of SalB nasal formulation.

Gut microbiota is a bridge between the metabolism and health state of the host,which plays a very important role in maintaining homeostasis. Natural polysaccharides,widely existed in nature,are a kind of biological macromolecules with prebiotics effects,which can improve a degree of physiological status by selectively changing the gut microbiota structure and function,enhancing the content of short chain fatty acids(SCFAs)and decreasing the level of inflammatory cytokines. In addition,the majority of polysaccharides can be degraded by gut microbiota to enhance their bioavailability and to promote the health state of the host. In this paper we discuss the interaction among polysaccharides and gut microbiotanatural,degradation mechanism and review gut microbiota as a target in the treatment of metabolic diseases,so as to provide future prospects of natural polysaccharides as " prebiotics " functional factors in the field of biological medicine and health products.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome