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.

Objective:To investigate the efficacy of stereotactic body radiotherapy (SBRT) combined with modified FOLFOXIRI (mFOLFOXIRI, irinotecan, oxaliplatin, leucovorin and fluorouracil) and cetuximab in the treatment of postoperative liver metastases in patients with KRAS, BRAF and NRAS gene wild-type colorectal cancer, and to evaluate treatment-related adverse reactions.Methods:A total of 86 patients with postoperative liver metastases from colorectal cancer diagnosed in Shandong Daizhuang Hospital from January 2018 to January 2021 were selected, all of whom were KRAS, BRAF and NRAS gene wild-type. All patients were divided into control group and study group according to the random number table method, with 43 cases in each group. The patients in the control group were treated with mFOLFOXIRI and cetuximab, 14 days a cycle, for a total of 12 cycles. The patients in the study group were treated with SBRT for liver metastases on the basis of the control group. Two patients in the control group were withdrawn from the study due to intolerance of myelosuppression (grade 4), and patients in the study group were withdrawn from the study due to intolerance of 1 case of myelosuppression, 1 case of gastrointestinal reaction and 1 case of abnormal liver function (all grade 4). The efficacy, median progression-free survival (PFS), median overall survival (OS) and adverse reactions were compared between the two groups after treatment.Results:After 12 cycles of treatment, the objective response rate (ORR) and disease control rate (DCR) of the study group were 55.00% (22/40) and 80.00% (32/40) respectively, which were higher than 31.71% (13/41) and 58.54% (24/41) of the control group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=4.37, P=0.037). After treatment, 14 patients (35.00%) in the study group were resectable, which was higher than 6 patients (14.63%) in the control group, with a statistically significant difference ( χ2=4.52, P=0.034). The median PFS and median OS of the study group were 9.2 months and 19.5 months respectively, which were longer than 6.5 months and 15.2 months of the control group, with statistically significant differences ( χ2=8.83, P=0.015; χ2=7.52, P=0.027). There were no significant differences in incidences of leukopenia [55.00% (22/40) vs. 46.34% (19/41), χ2=0.61, P=0.436], anemia [45.00% (18/40) vs. 39.02% (16/41), χ2=0.30, P=0.585], thrombocytopenia [37.50% (15/40) vs. 31.71% (13/41), χ2=0.30, P=0.584], nausea and vomiting [55.00% (22/40) vs. 48.78% (20/41), χ2=0.31, P=0.575], constipation and diarrhea [20.00% (8/40) vs. 17.07% (7/41), χ2=0.12, P=0.734], liver function damage [35.00% (14/40) vs. 29.27% (12/41), χ2=0.31, P=0.581], peripheral sensory neuropathy [30.00% (12/40) vs. 26.83% (11/41) ), χ2=0.10, P=0.752], acute cholinergic syndrome [12.50% (5/40) vs. 14.63% (6/41), χ2=0.08, P=0.779] and fatigue [52.50% (21/40) vs. 43.90% (18/41), χ2=0.60, P=0.439]. Conclusion:SBRT combined with mFOLFOXIRI and cetuximab is more effective than drug therapy alone in patients with liver metastases after colorectal cancer surgery, which can effectively prolong the survival period, and the adverse reactions are tolerable.

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 investigate treatment and outcome of rib cartilage framework in ear reconstruction. Methods: 12 cases of rib cartilage framework infection in ear reconstruction were retrospectively analysed in the latest four years. Lab examination results showed that staphylococcus aureus were found in 5 cases, coagulase negative staphylococcus in 3 cases, Klebsiella pneumonia in 2 cases, aeromonas hydrophila in 1 case and no bacteria were found in 1 case with regular culture. Debridement, systemic antibiotic therapy, saline irrigations and unobstructed drainage were utilized to treat the infection. Results: The average duration of dressing change was 35 days in 12 cases (12-67 days), of which six cases were cured leaving no obvious or mild change of cartilage framework. Cartilage framework was totally damaged by infection in one case, so the framework had to be removed and debridement was then carried out to control infection. Secondary repair should be taken at least 6 months later. In the rest 5 cases, frameworks were taken out in the early stage of infection. The infected portion of the cartilage was removed and the healthy part was buried subcutaneously in the chest. The expanded postauricular flap and fascia were smoothened. Secondary repair should be performed after 6 months. Conclusions Effective debridement, irrigations and drainage can be used to control infection of cartilage framework and maintain normal contour and structure of reconstructed auricle. With regards to severe infection, framework should be removed as early as possible and infected portion of cartilage should be cleared out, while healthy part could be used for secondary reconstruction of auricular contour after complete control of infection.

Objective To investigate the neuroprotective effect and possible mechanism of Compound Porcine Cerebroside and Ganglio-side Injection (CPCGI) on cerebral ischemia-reperfusion injury in rats. Methods Healthy adult male Sprague-Dawley rats were divided into sham group (n=10), model group (n=10), CPCGI low dosage group (n=10) and high dosage group (n=10), and control group (Ginkgo biloba extract, n=10). All the rats was subjected to middle cerebral artery occlusion (MCAO) for two hours and reperfusion except sham group, and received treatment for fourteen days once reperfusion started. They were tested with modified Neurological Severity Score one, three, seven and fourteen days after MCAO, and adhesive-removal test and beam-walking test fourteen days after MCAO. The expression of Beclin1, PINK1 and Parkin were detected with Western blotting. Results Compared with the model group, the Neurological Severity Score reduced (P<0.05) and the time crossing the beam reduced (P<0.01) in all the medical groups fourteen days after MCAO, and the time removing the adhesive paper reduced in the CPCGI groups (P<0.01). The expression of Beclin1 and Parkin decreased and the PINK1 level increased in the model group (P<0.01), and it was reversed in all the CPCGI groups (P<0.05). Conclusion CPCGI could relieve the cerebral ischemia-re-perfusion injury in rats through the regulation in mitophagy.

Objective To evaluate the effects of Guhong Injection on motor dysfunction in rats after cerebral ischemia- reperfusion. Methods The middle cerebral arteries were occluded for 2 hours and re-perfused in Sprague-Dawley rats. They were divided in sham group, model group, Aceglutamide group, Safflowere group and Guhong group, which were intravenously administrated with normal saline, Aceglutamide, Safflower or Guhong 24 hours after operation, and continued for 14 days. They were tested with the beam-walking test after treatment. Tyrosine hydroxylase (TH) immunohistochemical staining was used to investigate the viability of neurons in the substantia nigra. Results The model group spent more time in the beam-walking test than that in the sham group (P<0.01), and it decreased in the Safflower group and Guhong group compared with that in the model group (P<0.05). The TH-positive neurons decreased in the model rat compared with that in the sham group (P<0.001), and increased in both Safflower and Guhong groups compared with that in the model group (P<0.01). Conclusion Guhong administration could significantly improve the motor dysfunction in rats after cerebral ischemia- reperfusion, which might be related to provent the neurons from injury in the substantia nigra.

OBJECTIVETo investigate a novel method for the reconstruction of large vermilion defects.

METHODSBased on the size and shape of the defects, a buccinator myomucosal flap pedicled with the junction of buccinator and orbicularis oris in the oral commisure was designed and rotated to reconstruct the large vermilion defects. The upper bound of the flap is at least 1 cm away from the stensen's duct. The width is about 2.5-3.0 cm, and the length is as far as to arrive the raphe pterygomancibularis. The donate site is directly closed primarily. There is no need for secondary pedicle division.

RESULTSFrom July 2003 to April 2013, 14 cases with large vermilion defects was reconstructed with this method. No flap necrosis occurred with primary healing. 5 cases were followed up with an average follow up period of 1 year (0.5-3 years). The apprearance and function of the reconstructed vermilion were satisfactory without any apparent donor site defect. The patients were satisfied with both the functional and cosmetic results.

CONCLUSIONThe buccinator myomucosal flap is a simple and ideal method for reconstruction of large vermilion defects, especially for the defects closed to the commisure.

Adolescent ; Adult ; Child ; Facial Muscles ; surgery ; Female ; Follow-Up Studies ; Humans ; Lip ; surgery ; Male ; Mouth Mucosa ; surgery ; Surgical Flaps ; Young Adult

BACKGROUND:Currently, neural stem celltransplantation can be performed through three main approaches:local lesions, blood circulation, and cerebrospinal fluid.
OBJECTIVE:To review the transplantation of neural stem cells or neural precursor cells via the cerebrospinal fluid in the treatment of central nervous system diseases.
METHODS:A computer-based search of PubMed and CHKD databases was performed to retrieve articles concerning transplantation of neural stem cells via the cerebrospinal fluid, and its application and therapeutic mechanism in the treatment of central nervous system diseases in both animal experiment and clinic study published from 2000 to 2009.
RESULTS AND CONCLUSION:It is suitable for neural stem cellsurvival, proliferation, and differentiation in the cerebrospinal fluid. Transplantation of neural stem cells via the cerebrospinal fluid is effective and feasible to treat central nervous system diseases. However, some problems have not been solved, such as the source of neural stem cells, the optimal time window and celldose, the safety and the long-term effect. Further studies are needed to pave the way for the intrathecal injection of neural stem cells in the treatment of central nervous system diseases.