Humans ; Aortic Valve/surgery* ; Retrospective Studies ; Transcatheter Aortic Valve Replacement ; Sex Factors ; Heart Valve Prosthesis Implantation ; Treatment Outcome ; China ; Aortic Valve Stenosis/surgery* ; Risk Factors ; Risk Assessment

The 2030 Immunization Agenda of the World Health Organization （WHO） states that everyone in the world should fully benefit from vaccines to achieve good health and well-being. With the ever-changing disease spectrum and the improvement of residents' health literacy， relying solely on vaccines included in the National Immunization Program （NIP） is insufficient to meet the current requirements for disease prevention and control. Non-NIP vaccines play an important role in meeting people's diverse needs. Vaccine hesitancy is a global issue and an important factor affecting vaccine uptake. By reviewing relevant studies on vaccine hesitancy in recent years， this paper summarized different vaccination situations， current situation of vaccine hesitancy， measuring tools of vaccine hesitancy， and major influencing factors. It aims to provide references for the development of scientific and effective vaccine education strategies， which can increase public knowledge and understanding of vaccines， enhance healthcare professional's willingness and behavior in recommending vaccines， improve public vaccine literacy， and reduce vaccine hesitancy. At the same time， the supervision and guidance of media discourse should be strengthened to enhance the protective role of non-NIP vaccines in immunization barriers.

Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.

ObjectiveTo preliminarily explore the mechanism of Shufeng Tongluo prescription （SFTLP） in inhibiting airway inflammation in asthma mice by affecting the expression levels of eotaxin in the serum， CC type chemokine receptor 3 （CCR3）， and extracellular signal-regulated kinase （ERK） phosphorylation in lung tissues. MethodSeventy C57BL/6 mice were randomly divided into a blank group， a model group， low-， medium-， and high-dose SFTLP groups （7.75， 15.5， 30 g·kg^-1）， a pertussis toxin （PTX） group， a CCR3 inhibitor （SB328437） group， a phosphoinositide 3-kinase （PI3K） inhibitor （LY294002） group， a p38 protein kinase antagonist inhibitor （SB203580） group， and an ERK inhibitor （PD98059） group. The asthma model was induced in mice by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide ［Al（OH）₃］ combined with OVA atomization （0.2 mL for all）. After modeling， hematoxylin-eosin staining （HE staining） was used to observe the inflammatory infiltration of lung tissues in mice. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of eotaxin ［CC chemokine ligand （CCL） 11 and CCL24） in each group. Western blot was used to detect the levels of ERK phosphorylation and CCR3 in lung tissues. ResultCompared with the blank group， the model group showed obvious bronchial constriction， lumen stenosis， damaged alveolar structure， massive inflammatory cell infiltration in lung tissues， mucous plug in the bronchus， edema in the submucosal tissues of the trachea， increased folds， increased serum levels of CCL11 and CCL24 （P<0.01）， and increased expression of CCR3 protein in lung tissues （P<0.05）. The ERK levels in lung tissues of the model group and the PTX group increased （P<0.05）. The level of p-ERK in lung tissues of the model group and the low-dose SFTLP group increased （P<0.05）. As revealed by pathological results， compared with the model group， the high-dose SFTLP group showed relieved lung lesions. The high-dose SFTLP group and the SB328437 group showed reduced CCL11 content （P<0.05）. The low- and high-dose SFTLP group， the PTX group， the SB203580 group， the PD98059 group， and the SB328437 group showed decreased CCR3 protein expression in lung tissues （P<0.05）. The high-dose SFTLP group and the PD98059 group showed reduced p-ERK level （P<0.05）. The PD98059 group showed reduced ERK level （P<0.05）. ConclusionSFTLP can inhibit airway inflammation in asthma， and the mechanism may be related to the inhibition of eosinophil activation by down-regulating CCR3 and CCL11 expression and ERK phosphorylation.

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.

Objective To explore the feasibility of biplane-transesophageal echocardiography (Bip-TEE) in measuring the aortic annulus dimension (AAD).Methods Totally 24 patients underwent transcatheter aortic valve implantation (TAVI) were collected,and their AAD was measured by two-dimensional transthoracic echocardiography (2D-TTE),two-dimensional transesophageal echocardiography (2D-TEE),Bip-TEE and three-dimensional transesophageal echocardiography (3D-TEE) respectively.These four methods were compared with each other.The correlation between 3D-TEE measures and other three methods were analyzed.Results The AAD measured by 2D-TTE,2DTEE,Bip-TEE and 3D-TEE were (22.02±2.21)mm,(23.34±2.34)mm,(23.89±2.37)mm,(24.21±2.78)mm,respectively.The differences among 4 groups was significant (F=3.88,P=0.01).No statistically significant differences were found between Bip-TEE and 3D-TEE,2D-TEE and 3DTEE,Bip TEE and 2D-TEE (all P＞0.05).There were significant differences between 2D-TTE and 2D-TEE,2D-TTE and Bip-TEE,2D-TTE and 3D-TEE (all P＜0.05).The AAD measured by 3D-TEE were positively correlated with that of 2D-TTE,2D-TEE,Bip-TE (r=0.79,0.88,0.94,all P＜0.05).Conclusion Bip-TEE is a feasible method to measure the AAD rapidly and can provide reliable measurements for the prosthetic valve size in TAVI.

Objective To evaluate the clinical outcomes of internal fixation with extra-articular distal humerus locking compression plate (LCP) for the treatment of mid-distal humerus diaphyseal fracture.Methods From December 2012 to December 2016,a cohort of 22 patients with mid-distal humerus shaft fracture were treated by open reduction and internal fixation using extra-articular distal humerus LCP.They were 14 males and 8 females with an average age of 42.7 years (range,from 18 to 86 years).According to AO classification,there were 13 cases of type 12-A,7 cases of type 12-B,and 2 cases of type 12-C.The surgical time,intra-operative blood loss and hospital stay were recorded.The clinical outcomes were evaluated by the Mayo elbow performance score (MEPS) at the last follow-ups.Results Surgical time ranged from 46 to 95 minutes with an average of 57 minutes.The average blood loss was 220 mL (range,from 150 to 400 mL).The average hospital stay was 10.5 days (range,from 9 to 13 days).The mean follow-up was 23.8 months (range,from 6 to 48 months).Bone union was achieved in 21 cases after an average of 4.6 months (range,from 3 to 9 months),and one patient experienced bone non-union which was uneventfully healed after secondary auto platelet rich plasma (PRP) graft management.The average MEPS elbow performance score was 88.2,resulting in 16 excellent,4 fine and 2 fair cases (excellent and fine rate:90.9％).Conclusions Since extra-articular distal humerus LCP can provide stable internal fixation,facilitating early postoperative rehabilitation,it may be considered an effective alternative osteosynthesis for mid-distal comminuted humeral diaphyseal fractures.

Emerging evidence has indicated that BRCC 36-mediated K63-linked ubiquitination modification was involved in diverse cellular functions , including endocytosis , apoptosis and DNA damage repair .We previously showed that activation of cGMP/PKG pathway con-tributed to the binding of BRCC36 and the pro-fibrotic factor Smad3.The current study tested the hypothesis that BRCC 36 functions as a negative regulator of transforming growth factor-beta ( TGF-β)/Smad3 pathway and participates in cardiac remodeling .In isolated adult mouse cardiac fibroblasts , we have demonstrated that TGF-β1 treatment significantly increased the expression of BRCC 36.Over-expression BRCC36 suppressed TGF-β1-induced Smad3 phosphorylation, nuclear translocation, extracellular matrix molecular expres-sion and cell proliferation .On the contrary, silencing BRCC36 by transfection of adenovirus-carrying BRCC36 shRNA potentiated to
enhance the pro-fibrotic effect of TGF-β.In vivo, under chronic pressure overload condition-induced by transverse aortic constriction , myocardial pro-survival protein Bcl-2 and Mcl-1 expression were significantly decreased and the pro-apoptosis protein Puma was in-creased.However, the cardiac-specific over-expression of BRCC36 significantly increased myocardial Bcl-2 and Mcl-1 and inhibited Puma expression .Interestingly , we also found that sustained pressure overload resulted in a significant myocardial DNA injury in wild type mice, which was characterized by the increase of γH2AX level.However, cardiac-specific BRCC36 over-expression significantly decreased the level of γH2AX in the pressure overloaded heart in the transgenic mice , while effectively enhanced myocardial RAD 51 expression, a marker of DNA damage repair.Furthermore, BRCC36 over-expression effectively attenuated TAC-induced cardiac fibro-sis and remodeling in the transgenic mice , compared with the wild type mice .Collectively , the results have suggested that BRCC 36 ef-fectively protected heart against chronic pressure overload-induced cardiac remodeling though antagonizing TGF-β/Smad3 pathway and enhancing myocardial DNA injury repair response .

Objective To assess the effects of gastric bypass versus medical therapy in patients with obesity and type 2 diabetes. Methods The Cochrane library, Embase, PubMed, Chinese biomedical literature database and Wanfang database up to April 2014 were searched. Randomized controlled trails(RCTs) of frequently-used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results Four RCTs involving 157 patients in the gastric bypass groups and 152 patients in the medical therapy group were enrolled. Compared with medical therapy, gastric bypass for type 2 diabetes significantly decreased the levels of HbA1C(mean difference = -1. 85% , 95% CI -2. 15 ~ -1. 56, P< 0. 01), fasting blood glucose( standard mean difference = - 0. 90 mmol/ L, 95% CI-1. 24 ~ -0. 57, P<0. 01), body weight(mean difference=-23. 39 kg, 95% CI -29. 17 ~ -17. 61, P<0. 01), waist circumference(mean difference= -15. 36 cm, 95% CI -17. 51 ~ -13. 22, P<0. 01) and the dose of hypoglycemic medicine; while it increased the number of patients with HbA1C<6% (RR=5. 49, 95% CI 2. 22 ~ 13. 56, P<0. 01), the rate of adverse events(RR=1. 96, 95% CI 1. 42 ~ 2. 70, P<0. 01), and the level of high-density lipoprotein-cholesterol(mean difference=1. 24 mmol/ L, 95% CI 0. 64 ~ 1. 84, P<0. 01). Conclusions Gastric bypass surgery is more effective compared with medical therapy alone for obese patients with type 2 diabetes. Further intensive RCTs of high-quality in multiple centers with long-term follow-up should be carried out to provide more reliable evidences.

OBJECTIVE:To systematically review the efficacy of folic acid in the prevention of gastrointestinal(GI)tumors in elder,and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from Cochrane Library,PubMed,EM-Base,Web of Science,CMB,CJFD,VIP and Wanfang Database,the randomized controlled trials (RCT) about folic acid (test group)versus placebo(control group)in the prevention of GI tumors in elder(age>50 years old). After quality evaluation and da-ta extract,Meta-analysis was performed buy using Rev Man 5.3 statistics software. RESULTS:A total of 9 RCT were included,in-volving 29 494 patients. Results of Meta-analysis showed there was no significant difference in the incidence of GI tumors between 2 groups[RR=0.91,95%CI(0.74,1.12),P=0.38]. Results of subgroup analysis showed the incidence of GI tumors was not affected by GI tumor stage,age,basic serum folic acid level,type and dose of folic acid and follow-up time during follow-up period. CON-CLUSIONS:Folic acid supplement can not effectively prevent the incidence of GI tumors in elder. The incidence of GI tumors in elder with different ages and baseline of folic acid are not decreased by any dose and duration,without obvious adverse reactions. It indicates that folic acid supplement should be careful and give full conscideration to the patients’general situation. Due to the limit of methodological quality and sample size,it remains to be further verified with more rigorously designed and long-term follow-up of large-scale RCT.