Since 1986, the WHO has held ten global health promotion conferences covering various health promotion issues and sustainable development worldwide. These sessions have formed a series of consensus and actions that guide promoting health globally. This study analyzed the declarations, reports, and news materials from the ten conferences that studied health promotion action areas, focal topics, actor networks, partnership relationships, and other significant outcomes. It also explored how these conferences contributed to the construction and advancement of global health promotion consensus and actions. The first Global Conference on Health Promotion identified the concept of health promotion and five key action areas, laying the foundation for subsequent conferences and health promotion actions. Over the years, the ten conferences continuously expanded the essence of health promotion, developed partnership relationships, formulated public health promotion policies, and called for health promotion actions. This process culminated in the formation of global consensus and collective actions. The latter conferences have gained significant attention and influence. The conferences offer valuable insights for future global health promotion endeavors and provide global perspectives and pathways for the development of Healthy China.

Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats.Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic.Methods Thirty SD rats were randomly divided into normal,model and intervention groups(Guilin watermelon cream,8 mg/d for 7 days),with 10 rats/group.The oral mucosa of rats was subcutaneously injected with 10 g/mL of betel nut-extract to generate an oral ulcer model.The histomorphological changes were observed,and ulcer area and ulcer scores were assessed.Local oral tissue tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-8 levels were determined.Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method.Results Compared with rats in the normal group,those in the model group had an increased ulcer area,significantly increased ulcer scores(P＜0.01),and significantly increased levels of TNF-α,IL-2 and IL-8 in the oral mucosal tissues(P＜0.01).The amount Streptococcus(P＜0.05)and Veillonella(P＜0.001)in the oral saliva of the model group rats was significantly reduced.The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis,mucosal lamina propria edema,and hemorrhage accompanied by mass neutrophil and monocyte infiltration.Compared with the model group rats,the intervention group rats had significantly reduced ulcerated area(P＜0.05,P＜0.01)and ulcer scores(P＜0.05).And oral mucosal tissue levels of TNF-α(P＜0.01),IL-2(P＜0.05)and IL-8(P＜0.05),as well as significantly increased Streptococcus(P＜0.001)and Veillonella(P＜0.01)and significantly reduced Staphylococcus(P＜0.01)in the oral saliva.The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group.Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer,and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.

Ferrets offer an advantage in nonclinical studies of anti-infective drugs because of their ability to be infected with and spread pathogenic microorganisms,especially viral strains,without the need for host adaptation.Additionally,the clinical symptoms exhibited by infected ferrets are very similar to those of humans.Although ferrets play a very important role in the research and development of antiviral drugs,the scope of their application remains limited.This may be related to the lack of corresponding national standards for laboratory animal feeding and application of ferrets as well as the lack of specific diagnostic and detection reagents.This paper summarizes the characteristics of ferrets as infectious disease models with a summary and analysis of the application direction of ferrets in anti-infective drug research.Our aim is to promote further standardization of the use of ferrets.

Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies.Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group,and cyclophosphamide+fungal infection low,medium,and high dose groups,with 12 animals in each group.General clinical observations were performed daily,and the serum levels of immunoglobulin(Ig)G and IgM and galactomannan(GM)were detected by ELISA on the 3rd and 7th days of modeling.Simultaneously,the ratio of CD4+and CD8+cells,content of white blood cells(WBCs)and neutrophils(Neu)in peripheral blood,the Aspergillus niger load in alveolar lavage,and morphological changes to rat lung tissue were observed.Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling,and rats in the cyclophosphamide+fungal infection group also had shortness of breath and audible wet rhonchi in the lungs.Compared with the normal control group,rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+,WBC,Neu,IgG,and IgM in the blood,and their proportion of CD8+cells was significantly higher(P＜0.05,P＜0.01).Compared with the cyclophosphamide control group,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly reduced blood levels of IgG,IgM,and CD4+cells(P＜0.05,P＜0.01);while the cyclophosphamide+fungal infection low-,medium-,and high-dose groups had significantly reduced blood levels of WBC and Neu(P＜0.05,P＜0.01).Additionally,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly increased blood CD8+cells(P＜0.05,P＜0.01),Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide+fungal infection low-,medium-,and high-dose groups compared with the cyclophosphamide control group(P＜0.05,P＜0.01).The lung tissues of the cyclophosphamide+fungal infection low-,medium-,and high-dose groups showed mycelial distribution and destruction of alveolar epithelium,increase of bronchial epithelial cup cells in the alveoli,and infiltration of inflammatory cells,and the degree of lesions was positively correlated with the modeling dose.Conclusions In this study,we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease.The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time,confirming that cellular immunity plays an important role in the pathogenesis of the disease.At the same time,Ig can also affect the development of invasive pulmonary aspergillosis,and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.

Objective To investigate the potential mechanism of Jianpi Shenshi Formula for the treatment of hyperuricemia(HUA)by using network pharmacology and molecular docking techniques.Methods The active ingredients of Jianpi Shenshi Formula were searched and screened by combining TCMSP,BATMAN,and TCM-ID database with literature,and then SwissTargetPrediction was used to obtain the corresponding targets of the ingredients.Cytoscape 3.8.0 was used to construct a"drug-ingredients"network to analyze and obtain the main active ingredients of Jianpi Shenshi Formula.The GeneCards,OMIM,and disgenet databases were used to obtain the relevant targets of hyperuricemia.The intersection targets of Jianpi Shenshi Formula and hyperuricemia were imported into the STRING database for protein-protein interaction(PPI)network analysis,and hub targets for network were screened by CytoHubba plug-in.Meanwhile,the GO function and KEGG pathway enrichment analysis of the intersection targets were carried out using R4.2.2 software.Molecular docking of hub targets and key ingredients was performed using CB-DOCK 2.Results A total of 90 active ingredients of Jianpi Shenshi Formula were screened,among which quercetin,kaempferol,luteolin,stigmasterol,and ethyl linoleate were the main active ingredients,and 837 targets corresponding to the ingredients were obtained,with a total of 64 intersecting targets.CASP3,IL1B,IL6,PPARG,SIRT1,MAPK3,TNF,STAT3,TGFβ1,PTGS2,and XDH were the hub targets.The potential targets of action are mainly enriched in signaling pathways such as inflammation,metabolism,environment,cellular processes,biological systems,and hyperuricemia-related pathways.Conclusion Jianpi Shenshi Formula may exert effects on inhibition of uric acid production,and/or enhancement of uric acid excretion,anti-inflammation,and amelioration of related complications through the modulation of hyperuricemia-related signaling pathways(including neoplastic,infectious,metabolic,and cardiovascular diseases),as well as metabolic,immune,inflammatory,and other biological pathways by a variety of active ingredients such as quercetin,kaempferol,luteolin,stigmasterol,and ethyl linoleate.

Objective:To establish an animal model of pneumonia for research on clinical prevention and treatment of bacterial pneumonia by infecting immunocompromised rats with drug-resistant Acinetobacter baumannii ( Ab) strains. Methods:Drug-resistant Ab strains were selected. Forty-eight SD rats were randomly divided into four groups: normal group, cyclophosphamide control group (intraperitoneal injection of 45 mg/kg cyclophosphamide), bacterial infection group (intratracheal instillation of 1.5×10 8 CFU Ab suspension), and bacterial infection+ immunosuppression group (intraperitoneal injection of 45 mg/kg cyclophosphamide+ intratracheal instillation of 1.5×10 8 CFU Ab suspension). Flow cytometry analysis was used to detect the proportion of CD4 + , CD8 + and NK cells in rat peripheral blood before as well as 3 d and 7 d after infection. A lung function meter was used to detect peak inspiratory flow (PIF), peak expiratory flow (PEF), tidal volume (Vt ) and forced expiratory volume in the second second/forced vital capacity (FEV 200/FVC) at 3 d and 7 d after modeling. ELISA was used to detect the levels of IL-6, TNF-α and IL-10 in the alveolar lavage fluid. HE staining was used to observe the morphology of rat lung tissues in each group. Bacterial loads in rat lung tissues were counted by bacterial culturing. Results:A decrease in voluntary activity was observed in rats in the cyclophosphamide control group, bacterial infection group and bacterial infection+ immunosuppression group after modeling. Lung rales could be heard in the bacterial infection group and bacterial infection+ immunosuppression group. Compared with the normal group, the cyclophosphamide control group showed decreased proportion of CD4 + and CD11b + NK cells and increased CD8 + cells in peripheral blood; the bacterial infection group showed decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in the alveolar lavage fluid, and higher bacterial load in lung tissues with mild widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). Compared with the cyclophosphamide control group and the bacterial infection group, the bacterial infection+ immunosuppression group showed a lower proportion of CD4 + cells and a higher proportion of CD8 + cells in rat peripheral blood, decreased PIF, PEF, Vt and FEV 200/FVC, increased IL-6 and TNF-α levels and decreased IL-10 level in alveolar lavage fluid, higher bacterial load in lung tissues, and aggravated widening of alveolar walls and inflammatory cell infiltration ( P<0.05, P<0.01). The proportion of CD11b + NK cells in peripheral blood of rats in the bacterial infection+ immunosuppression group was significantly lower than that in the bacterial infection group ( P<0.05, P<0.01). Conclusions:A bacterial pneumonia model was successfully constructed by infecting rats with Ab alone or in combination with cyclophosphamide immunosuppression. In the model constructed with Ab and cyclophosphamide immunosuppression, the rats had more severe pneumonia, which might be related to the reduced cellular immune function and the aggravated bacterial infection in rat lung tissues by cyclophosphamide.

Objective:To explore the surgical strategy of coronary artery bypass grafting(CABG) for moderate ischemic mitral regurgitation(IMR), and to clarify the impact of mitral valve surgical intervention(MVS) on the long-term prognosis of such patients.Methods:The clinical data of 234 consecutive patients with moderate IMR who received CABG from January 2013 to December 2018 were retrospectively included, with 184 males and 50 females. The age ranged from 29 to 78 years, with a mean of(61.5 ± 8.7) years old. According to whether MVS was performed at the same time, they were divided into CABG group(108 cases, CABG alone) and CABG+ MVS group(126 cases, CABG+ MVS at the same time). The long-term cardiac events, all-cause deaths, major cardiovascular and cerebrovascular adverse events(MACCE) and other end events were followed up. A matching queue was established by propensity matching score for statistical analysis.Results:After propensity matching score, a matching queue was established, including 78 pairs of patients. Survival analysis showed that the incidence of long-term cardiac events and postoperative new onset atrial fibrillation in CABG+ MVS group was significantly higher( P<0.05). However, there was no significant difference between the two groups in all-cause mortality, cardiogenic mortality, and the incidence of MACCE events( P>0.05). Cox regression analysis showed that simultaneous CABG+ MVS was a risk factor for long-term cardiac events and new postoperative atrial fibrillation. The results of subgroup studies showed that for patients without tricuspid regurgitation before operation, left ventricular end diastolic diameter>55 mm, and left ventricular ejection fraction(LVEF) ≤0.55, the probability of cardiac events after MVS at the same time of CABG was higher( P<0.05). However, patients with no tricuspid regurgitation before operation, left ventricular end diastolic diameter>55 mm, LVEF≤0.55, and left atrial diameter≥40 mm had a higher probability of atrial fibrillation after MVS at the same time of CABG( P<0.05). Conclusion:CABG can improve left ventricular remodeling in patients with moderate IMR, whether MVS intervention is performed at the same time or not, and the long-term survival rate of both is similar. CABG+ MVS in the same period can maintain a low residual reflux, but the incidence of long-term cardiac events and arrhythmias is high. The longer-term prognosis needs to be further studied. The surgical strategy of such patients should be selected individually according to the specific situation and the surgical quality in medical centers.

Objective:To evaluate the characteristics of diastolic left intraventricular pressure differences(IVPD) and intraventricular pressure gradients(IVPG) among normal adults in different ages by vector flow mapping.Methods:From March 2019 to October 2020, 1 093 healthy volunteers were selected from the physical examination center of the Second Affiliated Hospital of Harbin Medical University, and they were divided into youth group (18-40 years old), middle-aged group (41-65 years old) and elderly group (>65 years old). IVPD and IVPG during isovolumetric relaxation(IR) period, rapid filling (RF) period, slow filling(SF) period, and atrial contraction(AC) period were measured by vector flow mapping, and were correlated with left ventricular diastolic function parameters.Results:①IVPD-IR, IVPD-AC, IVPG-IR, and IVPG-AC gradually increased while IVPD-RF, IVPD-SF, and IVPG-RF gradually decreased from the youth group to the elderly group(all P<0.05). ②IVPD-RF and IVPG-RF were positively correlated with E( r=0.391, 0.402, P<0.001, respectively). IVPD-AC and IVPG-AC were positively correlated with A( r=0.407, 0.425, P<0.001, respectively) and E/e′( r=0.268, 0.294, P<0.001, respectively) while negatively correlated with E/A( r=-0.510, -0.506, P<0.001, respectively) and e′/a′( r=-0.514, -0.511, P<0.001, respectively). Conclusions:IVPD and IVPG can quantitatively analyze the changes of left ventricular hemodynamics in normal subjects, which are expected to be new indexes to evaluate left ventricular diastolic function.

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .

Objective To evaluate the clinical outcomes and prognosis of older human immunodeficiency virus (HIV )-infected patients under antiretroviral therapy (ART ) in China .Methods This study was carried out in a retrospective cohort of HIV-infected patients initiated ART between January 2004 and December 2012 at The First Affiliated Hospital ,China Medical University .The patients were enrolled and divided into two groups ,including <50 years group (young and middle-aged group) and≥50 years group (older group) .Immunological and virological responses and mortality were analyzed . Data were analyzed by t test ,chi-square test ,two-way analysis of variance and log-rank test .Results Totally 291 subjects were included ,among whom 97 subjects were older patients and 194 subjects were young and middle-aged patients .Male was predominate in both groups ,which accounted for 91 .8％ and 87 .6％ ,respectively .The CD4+ T lymphocyte count in the older group before treatment was (151 .9 ±96 .2) cells /μL ,which was significantly lower than that in the young and middle-aged group (183 .4 ± 93 . 5) cells/μL (t= 2 .657 , P=0 .009) .At month 12 of treatment ,the CD4+ T lymphocyte count in the older group was significantly lower than that in the young and middle-aged groups (t= 2 .120 , P=0 .035) ,while there was no statistically significant difference between the two groups at month 24 (t=1 .025 ,P=0 .299) .The percentage of CD4+ T lymphocyte count increasing to 500 cells/μL in the older and youth groups during follow-up were 11 .3％ and 16 .0％ ,respectively (χ2=1 .127 ,P =0 .376) .Log-rank analysis showed that the mean times of virus inhibition in older group and young and middle-aged group were 7 .9 (95％ CI:6 .8-8 .5) and 7 .6 (95％ CI:6 .5 -9 .3) ,respectively ,with no statistically significant difference (χ2 =0 .002 , P=0 .961) .Virological failure was reported in 4 patients (4 .1％ ) in older group and 11 patients (5 .7％ ) in young and middle-aged group . Chi-square test showed no statistically significant difference between the two groups (χ2 = 0 .15 , P= 0 .78) .During follow-up , 19 .6％ (19/97) in older group and 3 .6％ (7/194) in young and middle-aged group died .The former was significantly higher than the latter (χ2 = 21 .113 , P< 0 .01 ) .Conclusions Older patients show a poor immunologic response ,similar viral suppression and higher risk of mortality compared with young and middle-aged patients . Future research should be aimed at the feasible and specific strategy for early diagnosis and timely treatment for older patients to improve treatment efficacy and reduce mortality .