Objective:To explore the abundance, diversity, and structural changes of early postoperative pulmonary bacterial microbiota in lung transplant recipients.Methods:Recruiting 40 recipients who underwent lung transplantation surgery at the First Affiliated Hospital of Guangzhou Medical University from October 2020 to May 2022 for the study.All recipients did not receive antibiotic treatment within 4 weeks prior to surgery, and all recipients received a unified immunosuppressive and anti infection regimen after surgery.The bronchoalveolar lavage fluid(BALF) was collected from the amputated lung in vitro before the transplantation for 16S ribosomal RNA sequencing and flora analysis.BALF was also collected at the scheduled time from the transplanted lung on the 7th, 14th and 30th days post transplantaion for analysis.Results:The study included a total of 40 recipients who did not receive antibiotic treatment within 4 weeks before surgery, including 35 males.Among the study participants, there were 14 cases of primary obstructive pulmonary disease, 19 cases of interstitial lung disease, 3 cases of occupational lung disease, and 4 others.Microbiome in BALF of transplanted and detached autologous lungs at the first week after surgery α( P<0.05) and β diversity is statistically significant( R2=0.08, P=0.001), and the bacterial community in the transplanted lungs α Diversity is lower than that of explant lungs.Starting from the second week after surgery, the richness and species diversity of the transplanted lung microbiota gradually increase.The bacterial structure was also changed with postoperative time, and the relative abundance of the same bacterial species were varied at different time points.The bacterial community in BALF was mainly dominated by Proteobacteria both explant lungs and transplant lungs.The relative abundance of Staphylococcus and Acinetobacter genera at the BALF in transplanted lungs was higher than that in explant lung samples, but their relative abundance decreased over time after surgery. Conclusions:The α diversity of the early postoperative pulmonary microbiota after lung transplantation was lower than that of the amputated autologous lung, and the bacterial richness and species diversity in the microbiota of the transplanted lung gradually increased at the second week after the transplantation.The bacterial microbiota of the transplanted lung is changed complicatedly with time.

AIM To explore the clinical effects of San'ao Decoction combined with salbutamol on patients with cough variant asthma.METHODS Eighty patients were randomly assigned into control group(40 cases)for 3-month administration of salbutamol,and observation group(40 cases)for 3-month administration of both San'ao Decoction and mifepristone.The changes in clinical efficacy,TCM syndrome scores,serum MMP-9,VEGF and sex hormones(E2,FSH,PRL)and incidence of adverse reactions were detected.The changes in clinical efficacy,EOS,SIgG4,TIgE,Eotaxin,NKA,LTD4,IL-27,SP,R5-R20,Fres,R5,Zrs,PEF diurnal variation rate,FEF25,PEF,ACT score,PAQLQ score,recurrence rate and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with lower recurrence rate(P<0.05).After the treatment,the two groups displayed decreased EOS,TIgE,Eotaxin,NKA,LTD4,SP,R5-R20,Fres,R5,Zrs and PEF diurnal variation rate(P<0.05),and increased SIgG4,IL-27,FEF25,PEF,ACT score,PAQLQ score(P<0.05),especially for the observation group(P<0.05).No significant difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with cough variant asthma,San'ao Decoction combined with salbutamol can improve EOS,TIgE,Eotaxin,SIgG4 levels and airway resistance indices,lung function indices,regulate neurogenic mediators,alleviate airway inflammation injury,enhance life quality,and reduce recurrence rate.

As a modern dosage form drug with rapid effect, traditional Chinese medicine (TCM) injection has been more and more used in clinical practice. Meanwhile the safety of TCM injection has attracted more and more attention. The retrospective analysis on 74 cases of adverse reaction of TCM injections collected from 2007 to 2016 in the Third Affiliated Hospital of Beijing University of Chinese Medicine showed that the proportion of men and women with adverse reactions was 0.54:1; the average age was 62.5 years old; 21 kinds of TCM injections were involved. Among them, the most reported were blood-regulating agents. The top four kinds of TCM injections with highest adverse drug reactions (ADRs) were Tanreqing injection, Danhong Injection, Shuxuening Injection and Xuesaitong for injection. The top three clinical manifestations of adverse reactions were lesions of skin and its appendages, damage of circulatory system and damage of nervous system. The potential causes of the adverse reactions of TCM injections were analyzed, and it was believed that individual difference, medicine, pharmaceutical excipients, solvent and TCM syndrome differentiation may be the main five causes for the adverse reactions of TCM injections. In order to reduce the adverse reactions of TCM injections, it is suggested that the clinical pharmacists should participate in the application management of TCM injections in the hospital; the production enterprises shall strengthen the whole life cycle management of the drugs; and at the same time, the drug control and administration authorities should improve the drug management methods constantly and encourage the development of TCM injections to the high quality level.
Drugs, Chinese Herbal ; adverse effects ; Female ; Humans ; Injections ; adverse effects ; Male ; Medicine, Chinese Traditional ; adverse effects ; Middle Aged ; Retrospective Studies

Newcastle disease virus (NDV) and Salmonella Pullorum have significant damaging effects on the poultry industry, but no previous vaccine can protect poultry effectively. In this study, a recombinant-attenuated S. Pullorum strain secreting the NDV hemagglutinin-neuraminidase (HN) protein, C79-13ΔcrpΔasd (pYA-HN), was constructed by using the suicide plasmid pREasd-mediated bacteria homologous recombination method to form a new bivalent vaccine candidate against Newcastle disease (ND) and S. Pullorum disease (PD). The effect of this vaccine candidate was compared with those of the NDV LaSota and C79-13ΔcrpΔasd (pYA) strains. The serum hemagglutination inhibition antibody titers, serum immunoglobulin G (IgG) antibodies, secretory IgA, and stimulation index in lymphocyte proliferation were increased significantly more (p < 0.01) in chickens inoculated with C79-13ΔcrpΔasd (pYA-HN) than with C79-13ΔcrpΔasd (pYA) but were not significantly increased compared with the chickens immunized with the LaSota live vaccine (p > 0.05). Moreover, the novel strain provides 60% and 80% protective efficacy against the NDV virulent strain F48E9 and the S. Pullorum virulent strain C79-13. In summary, in this study, a recombinant-attenuated S. Pullorum strain secreting NDV HN protein was constructed. The generation of the S. Pullorum C79-13ΔcrpΔasd (pYA-HN) strain provides a foundation for the development of an effective living-vector double vaccine against ND and PD.
Animals ; Antibodies ; Bacteria ; Chickens ; Hemagglutination ; HN Protein ; Homologous Recombination ; Immunoglobulin A, Secretory ; Immunoglobulin G ; Lymphocytes ; Methods ; Newcastle disease virus ; Newcastle Disease ; Plasmids ; Poultry ; Salmonella ; Suicide ; Vaccines

To investigate the effect and mechanism of miR-498 on Th17 cell differentiation of peripheral blood mononuclear cells (PMBCs) in rheumatoid arthritis (RA) patients, peripheral blood samples were collected from RA patients and healthy controls, respectively. The proportion of CD4IL-17 T cells (Th17 cells) or CD4FOXP3 T cells (Tregs) in T cells and the Th17/Treg ratio were identified by the flow cytometer. The STAT3 and miR-498 expression were measured by Western blot and real-time PCR, respectively. ELISA was used to detect IL-17 concentrations. Luciferase assay was performed to confirm that miR-498 directly targeted the 3' untranslated region (3'UTR) of STAT3 in CD4 T cells. The effect of miR-498 on Th17 cell differentiation was explored by transfection of miR-498 mimic and/or pcDNA-STAT3 into CD4 T cells. In PMBCs of RA patients, the Th17/CD4 T cell ratio was significantly increased, while the Tregs/CD4 T cell ratio was obviously decreased, leading to a higher Th17/Treg ratio. The results showed a reduced miR-498 expression and an increased STAT3 protein expression in PMBCs, and an increased IL-17 concentration in serum of RA patients. In cells transfected with wild-type-STAT3-LU, miR-498 mimic significantly reduced the luciferase activity, STAT3 gene and protein expression, and miR-498 inhibitor had an opposite function. While the miR-498 mimic/inhibitor had no effect on the luciferase activity and STAT3 expression in cells transfected with mutant-STAT3-LU. CD4 T cells transfected with miR-498 mimic had a lower Th17/CD4 T cell ratio and IL-17 concentration, however, transfection of pcDNA-STAT3 reversed the effect of miR-498 mimic on Th17/CD4 T cell ratio and IL-17 concentration. These results suggest that overexpression of miR-498 suppresses Th17 cell differentiation by targeting STAT3 in RA patients.

Objective To observe the acute toxicity and nephrotoxicity of antibacterial peptide R9 in mice.Methods Median lethal dose (LD50) test:Antimicrobial peptide R9 was intraperitoneally injected into mice.After 7 d of observation,the LD50 and 95 ％ confidence limits were calculated according to the Bliss method.Renal toxicity of R9 test:80 mice were randomly divided into 4 groups:the low,medium and high dose (6.7,10,15 mg · kg-1 R9) experimental groups and blank control group (distilled water) were injected intraperitoneally.The blood samples were collected on the 2nd day respectively from 10 mice,then blood indexes were tested.The serum were separated,then creatinine,blood urea nitrogen and total protein were measured.Kidneys and other organs were taken to calculate the organ coefficients.Results The LD50 of antimicrobial peptide R9 was 21.3 mg · kg-1,and its 95％ confidence limit was 19.1-23.5 mg · kg-1.On the second day after administration,WBC (4.07 × 109/L) and RBC (8.96 × 1012/L) in the high dose experimental group decreased compared with the blank control group,the differences were statistically significant difference (P ＜ 0.01,P ＜ 0.05).Creatinine (19.99 μmol · L-1) and urea nitrogen (8.07 mmol · L-1)increased with significant (P ＜0.05,P ＜ 0.01).The total protein (54.18 g · L-1) decreased with significant (P ＜0.05) and the kidney coefficient (13.40 mg· g-1) increased with significant (P ＜ 0.05).Conclusion A single intraperitoneal injection of antimicrobial peptide R9 can produce certain toxicity to mice,and the kidney was the main target organ.Nephrotoxicity was positively correlated with dose,and there was a trend of reversible improvement after withdrawal.

OBJECTIVETo investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats.

METHODSTwo-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin β-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot.

RESULTSCompared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and β-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05).

CONCLUSIONSDEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.

AIM:To investigate the change of late sodium current (INaL) and the effect of Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) inhibitor KN-93 on INaLin the cardiomyocytes after isoproterenol-induced heart fai-lure (HF) in rabbits. METHODS:The rabbit model of HF was induced by injecting isoproterenol (300 μg·kg-1· d-1) for 15 d. One month later, all rabbits received by echocardiography and HE staining to observe the morphological changes of myocardium for evaluating the HF model. The protein expression of NaV1.5, CaMKⅡδ and phosphorylated CaMKⅡδ was determined by Western blot. The ventricular myocytes were isolated from the rabbits of normal saline(NS) group and HF group by Langendorff perfusion, and the whole-cell patch-clamp technique was used to record INaL. RE-SULTS:Compared with NS group,the heart rate in HF group was increased (P<0.01), the ventricular cavity was en-larged (P<0.05),and the cardiac function was decreased(P<0.01). Compared with NS group,the cardiomyocytes in HF group arranged in disorder, vacuolar degeneration and myocardial interstitial edema were observed, and fibrous tissue increased. The protein levels of NaV1.5,CaMKⅡδ and phosphorylated CaMKⅡδ in HF group were higher than those in NS group(P<0.01). INaLin HF group significantly increased compared with NS group (P<0.01). After adding sea anemone toxin Ⅱ (ATXⅡ), the density of INaLin HF group and NS group was significantly increased, but that in HF group increased more obviously than that in NS group (P<0.01). After ATXⅡ had induced stable current, we added KN-93 into NS group and HF group,and we found that the ATXⅡ-increased INaLin NS group and HF group was signifi-cantly decreased(P<0.05).CONCLUSION:CaMKⅡinhibitor KN-93 inhibits the increase in INaLin HF rabbits,which may be related to the activity of CaMKⅡδ and the regulation of CaMKⅡ δ on INaL.

Atrial fibrillation ( AF) is the most common arrhythmia in clinical practice .Mitochondrial oxidative stress is supposed to contribute to development , progression and self-perpetuation of AF .Reactive oxygen species ( ROS) is the major molecule mediating mitochondrial oxidative stress damage .ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensi -tive signal transduction pathways .Eventually , it leads to atrial electrical remodeling and promotes the development of AF . Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation .

OBJECTIVETo clarify the protective roles of compatibility of geniposide and ginsenoside (Rg1) in regulating ischemia injured microglia homeostasis by comparing the difference in regulatory roles of geniposide, Rg1, or ginsenoside + Rg1 in balancing secretion of oxygen glucose deprivation induced microglia inflammatory cytokines.

METHODSThe mimic ischemia injured microglia model was induced by oxygen-glucose deprivation (OGD). Then geniposide, Rg1, or ginsenoside + Rg1 (Tongluo Jiunao Injection, TJI) was respectively added. The NO content was determined by Griess Reagent. The cyto activity was detected using cell count kit. Contents of TNF-alpha and TGF-beta and their expression levels were detected by ELISA and Western blot.

RESULTSGeniposide + Rg1 could significantly inhibit the release of NO, elevate the TGF-beta level, and decrease the content of TNF-alpha without influencing the cell survival. The two active ingredients played different therapeutic roles. The compatible use was obviously superior to use any one of the two active ingredients alone.

CONCLUSIONSGeniposide, Rg1, or Ginsenoside + Rg1 had regulating roles in balancing ischemia injured microglia homeostasis. Its mechanisms might be related to up-regulating the TGF-beta expression and down-regulating TNF-alpha expression.

Animals ; Ginsenosides ; pharmacology ; Hypoxia ; metabolism ; Iridoids ; pharmacology ; Mice ; Microglia ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism