Objective To investigate the therapeutic effects of a newly constructed Aβ25-35-based recombinant gene vaccine for Alzheimer's disease(AD).Methods The pcDNA-Aβ25-35-GRP94 recombinant gene vaccine was con-structed using Aβ25-35 as the epitope and pcDNA3.1 plasmid as the vector.Early APP/PS1 double-transgenic mice were selected as experimental subjects,including the AD control group and the pcDNA-Aβ25-35-GRP94 immunized group for regular immunization.ELISA was performed to detect the titers and isotypes of Aβ-specific antibodies;Morris Water Maze(MWM)Test and Open-Field Test(OFT)were performed to determine the changes in both cognitive ability and mental state of mice;Immunohistochemistry was used to assess the effects of the vac-cine on both Aβ plaques and glial cells in the brains of AD mouse models;ELISA kit was used to evaluate the level of inflammatory factors(TNF-α,IL-1β)in the mouse brain.Results Compared with the AD control group,the pcDNA-Aβ25-35-GRP94 vaccine induced APP/PS1 mice to produce higher levels of Aβ specific antibodies(P<0.05),and mainly induced IgG1 antibodies(P<0.01).The vaccine significantly reduced Aβ plaques in the brain tissue(P<0.05)and effectively alleviated learning memory impairment in APP/PS1 mice(P<0.05)without causing mental behavioral abnormalities.Moreover,the vaccine inhibited the abnormal proliferation of glial cells(P<0.05)and did not cause obvious inflammatory reactions in the brain,suggesting the vaccine was safe and effective.Conclusions Early vaccination with a Aβ25-35-based recombinant gene vaccine can induce the formation of high level of Aβ specific antibodies,effectively alleviate the learning memory impairment of AD and related neu-ro-pathological changes.It may be used to treat AD.

Objective To construct fluorescent molecular probes targeting at tumor heat shock protein 90(Hsp90)in order to enhance tumor-specific recognition.Methods The human pancreatic adenocarcinoma cell line PANC-1 and the human small cell lung cancer cell line NCI-H446 were used as the research targets to study the uptake and clearance of Cy5-P7 by tumor cells with flow cytometry as well as immune-fluorescence technology;The mechanism to mediate entrance of Cy5-P7 into the cells by Hsp90 was investigated by blocking of the PANC-1 cell surface pro-teins with monoclonal antibody to Hsp90;Human pancreatic cancer cell line PANC-1 was subcutaneously injected into posterior dorsum of BALB/c nude mice to construct a xenogeneic subcutaneous tumor model to validate the in vivo tumor recognition ability by Cy7-P7 as well as its in vivo distribution in mice.Results The uptake of Cy5-P7 by cells was significantly reduced in low temperature(P<0.05);An average fluorescence intensity in Cy5-P7-trea-ted cells was significantly reduced after blocking with a monoclonal antibody to Hsp90(P<0.05);The fluorescence intensity at the tumor site of Cy7-P7 group was higher than that of control group(P<0.05),and there was a significant presence of Cy7-P7 in the kidney and tumor fluorescence.Conclusions Cy5-P7 can effectively target at Hsp90,and its specific binding significantly enhanced the cellular uptake of Cy5-P7 fluorescent probe,which im-proved the sensitivity and accuracy of fluorescence imaging.Cy7-P7 showed good tumor active recognition in vivo,and was able to be enriched at the tumor site and metabolized out of the body in 48 h,which may effectively sup-port accurate tumor recognition.

Protein translational reprogramming is an important compensatory change made by cells in response to a variety of stimuli,resulting in rapid,specific changes to the cellular proteome.In tumor cells,this reprogramming is regulated through several mechanisms,including the internal ribosome entry site(IRES),cap-independent translational enhancers(CITE),and N6-methyladenosine(m6A)modifications.These processes play pivotal roles in controlling protein translational reprogramming,which is essential for tumorigenesis,progression,and treatment resistance.Further research into the function of protein translational reprogramming in tumors may reveal novel ther-apeutic targets and offer new avenues for cancer treatment.

As for the treatment of microtia, the status quo is as follows. The ear reconstruction with autologous costal cartilage has been generally accepted as the therapeutic strategy for type Ⅲ/Ⅳ patients with only small ear lobe remaining or complete absence of auricle, and the outcomes are improved steadily with the advances in technology; but for type Ⅰ/Ⅱ patients with larger remnant ear, there is insufficient evidence to be able to support any specific treatment methods as the potential unified approach for surgeons to choose from. Non-surgical treatment with appliance wearing may play an auxiliary role in the treatment of microtia, which is worthy of further research. The authors proposed a serialized treatment system based on their clinical practice and literature review. It is expected to be helpful for the treatment of microtia.

As for the treatment of microtia, the status quo is as follows. The ear reconstruction with autologous costal cartilage has been generally accepted as the therapeutic strategy for type Ⅲ/Ⅳ patients with only small ear lobe remaining or complete absence of auricle, and the outcomes are improved steadily with the advances in technology; but for type Ⅰ/Ⅱ patients with larger remnant ear, there is insufficient evidence to be able to support any specific treatment methods as the potential unified approach for surgeons to choose from. Non-surgical treatment with appliance wearing may play an auxiliary role in the treatment of microtia, which is worthy of further research. The authors proposed a serialized treatment system based on their clinical practice and literature review. It is expected to be helpful for the treatment of microtia.

Radiation-induced lung injury is a common complication of thoracic malignant tumor radiotherapy and severe nuclear accident injury. Currently, there is no effective treatment on this injury. Mesenchymal stem cells (MSCs) are a group of cells with multi-directional differentiation potential and they can protect lung tissue from radiation damage by homing to the injured site and differentiating to the damaged tissues, secreting cytokines and immune regulation. Further, the genetically modifying mesenchymal stem cells have not only the main characteristics of MSCs, but also can efficiently and stably express or knock down a certain of target genes, thereby enhancing or reducing the sensitivity of mesenchymal stem cells to various physiological stimulus and enhancing its therapeutic effect in radiation-induced lung injury, providing new ideas and new strategies for clinical treatment. This paper reviewed the relevant research progress in recent years.

Objective:To evaluate the role of de novo mutations (DNMs) in Chinese patients with non-syndromic congenital microtia by using whole exome sequencing in patient-parent trios and to detect the pathogenic DNMs, if there are any. Methods:Twenty-four Chinese trio families with congenital microtia were recruited from March 2017 to July 2018 at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. The patients, aged from 6 to 10 years old, 15 males and 9 females, had unilateral microtia, including 15 on the left and 9 on the right. After informed consent, peripheral blood was collected from patients and their unaffected parents.Whole exome sequencing was performed on all patients and their parents. DNMs in the coding region and canonical splicing sites were detected, and the number of DNMs in each patient was obtained. Each DNM was classified according to the ACMG standards and guidelines for the interpretation of sequence variants. In-silico prediction was performed using different algorithms and databases considering both variant-and gene-level implications. ExAc database, VarCards, Human Splicing Finder 3.1 software were used to predict each variant’s pathogenicity, including loss of function variant, missense variant and nonsynonymous variant. Mouse genome information database was used to detect the expression of the homologous gene, and David 6.8 bioinformatics database was used for pathway enrichment analysis of candidate genes. The Online Mendelian Inheritance in Man database was used to query the correspondence between candidate genes and human diseases.Results:Twenty-three DNMs were detected in 24 microtia trios. In each patient, there was 0-3 DNMs with no significant difference in population. Twelve missense variants, eight synonymous variants, one nonsense, one start codon variant, and one inframe indel were detected. Among them, a nonsense LRP12 mutation was classified as pathogenic according to ACMG guidelines. However, none of the variants were considered disease-causing according to in-silico predictions.Conclusions:Increased number or mutational burden of DMNs are not observed in Chinese patients with microtia. DMNs is not the primary cause of microtia, although rare DNMs in responsible genes could occasionally lead to cases.

Objective:To evaluate the role of de novo mutations (DNMs) in Chinese patients with non-syndromic congenital microtia by using whole exome sequencing in patient-parent trios and to detect the pathogenic DNMs, if there are any. Methods:Twenty-four Chinese trio families with congenital microtia were recruited from March 2017 to July 2018 at the Plastic Surgery Hospital of Chinese Academy of Medical Sciences. The patients, aged from 6 to 10 years old, 15 males and 9 females, had unilateral microtia, including 15 on the left and 9 on the right. After informed consent, peripheral blood was collected from patients and their unaffected parents.Whole exome sequencing was performed on all patients and their parents. DNMs in the coding region and canonical splicing sites were detected, and the number of DNMs in each patient was obtained. Each DNM was classified according to the ACMG standards and guidelines for the interpretation of sequence variants. In-silico prediction was performed using different algorithms and databases considering both variant-and gene-level implications. ExAc database, VarCards, Human Splicing Finder 3.1 software were used to predict each variant’s pathogenicity, including loss of function variant, missense variant and nonsynonymous variant. Mouse genome information database was used to detect the expression of the homologous gene, and David 6.8 bioinformatics database was used for pathway enrichment analysis of candidate genes. The Online Mendelian Inheritance in Man database was used to query the correspondence between candidate genes and human diseases.Results:Twenty-three DNMs were detected in 24 microtia trios. In each patient, there was 0-3 DNMs with no significant difference in population. Twelve missense variants, eight synonymous variants, one nonsense, one start codon variant, and one inframe indel were detected. Among them, a nonsense LRP12 mutation was classified as pathogenic according to ACMG guidelines. However, none of the variants were considered disease-causing according to in-silico predictions.Conclusions:Increased number or mutational burden of DMNs are not observed in Chinese patients with microtia. DMNs is not the primary cause of microtia, although rare DNMs in responsible genes could occasionally lead to cases.

Objective To explore the key initiatives and effective methods for preparing the constructions of emergency-oriented hospitals under COVID-19 pandemic. Methods The wartime mechanism was strengthened by adhering to unified leadership, trengthening the top-level design and clarifying the division of responsibilities. Objective management was used as a means to take into account the key of personnel allocation and training, prevention and control of hospital infection, transformation of contagious ward, logistic support, equipment and material supply and construction of system and process. Results The preparations and constructions of the emergency-oriented hospitals were completed in 72 hours，which passed the acceptance and inspections from infection control experts，who appraised our work to be “the highest in difficulty, the fastest in project progress and the highest in quality". Totally, upon to the preparations，14 medical teams were set up and the layout process reestablishment of 14 wards was completed, the installation and preparation of nearly 10000 sets/pieces of medical equipment and medical materials were completed as well and more than 80 work systems and process systems for 9 major modules were established. Conclusion The preparations and constructions of emergency-oriented hospitals should be performed upon the thorough implementation of the decisions and arrangements by the municipal Party committee and the municipal government, insisting on the wartime thinking and establishment of high-quality management team and effective goal management focusing on details and actual needs of medical staff.

Objective: To study the expression of Wnt2b protein and the epithelial-mesenchymal transition related markers in tissues of carcinoma of bile duct and normal bile duct to determine the clinical significance. The relationships between the expression levels and clinicopathological characteristics were analyzed, and the correlation between Wnt2b and epithelial interstitial transformation (EMT), tumor invasion and metastasis were studied. Methods: A total of 60 patients with cholangiocarcinoma and 30 patients with normal bile duct tissues admitted to the Affiliated Hospital of Qingdao University from December 2008 to December 2013 were studied. The expressions of Wnt2b, E-cadherin and Vimentin protein were detected by SP immunohistochemical staining. The patients were classified according to the expressions of these proteins. Analyses were conducted on the relationships of these proteins with clinical characteristics of the patients with cholangiocarcinoma. Results: The positive expression rate of Wnt2b protein in carcinoma of bile duct tissues was 90.0%, which was significantly higher than that in normal bile duct tissues (χ²=38.1, P<0.05). The positive expression rate of Wnt2b in T₃ + T₄ was significantly higher than that in T₁ + T₂ (P<0.05). There were no correlations of the expression with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). Patients with lymph node metastasis had a significantly higher positive expression of Vimentin than patients with no lymph node metastasis, and the loss of E-cadherin expression was increased (all P<0.05). There were no relationship of the expressions of these proteins with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). The increased expression of Wnt2b in bile duct cancer cells was related to increase in EMT marker of the positive expression of vimentin and the loss of E-cadherin expression (both P<0.05). Conclusions Wnt2b protein overexpression in cholangiocarcinoma correlated with epithelial-mesenchymal transition related markers. The Wnt2b protein was correlated with cholangiocarcinoma occurrence, development, invasion and metastasis. Wnt2b has the potential to develop into a new therapeutic target for carcinoma of bile duct.