Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

目的：筛选果蝇Zeste基因增强子同源物2（EZH2）基因上游miRNA及lncRNA，分析其在胃癌细胞中的表达并验证其间的靶向关系，探讨它们对胃癌细胞增殖、迁移和凋亡的影响。方法：通过ENCORI、miRDB和Target Scan数据库查询并分析、筛选EZH2上游miRNA（has-miR-450b-5p），ENCORI数据库和DAINA数据库筛选has-miR-450b-5p上游lncRNA（lncRNA NEAT1），预测hsa-miR-450b-5p、lncRNA NEAT1与EZH2之间的结合位点，双荧光素酶报告基因实验验证hsa-miR-450b-5p与lncRNA NEAT1的结合关系。采用qPCR和WB法检测lncRNA NEAT1和EZH2在正常胃黏膜细胞（GES-1）与胃癌细胞（MGC-803、SGC-7901和MKN-28）中的表达量。按转染物的不同将MGC-803和SGC-7901细胞分为hsa-miR-450b-5p-mimic组、mimic-NC组、si-NEAT1组和si-NC组，转染36~48 h后qPCR法验证过表达及敲减效果；通过qPCR、WB法检测观察过表达hsa-miR-450b-5p对细胞中lncRNA NEAT1和EZH2 mRNA、蛋白表达的影响，以及敲减lncRNA NEAT1对hsa-miR-450b-5p和EZH2 mRNA表达的影响；CCK-8法、划痕愈合实验和流式细胞术分别检测敲减EZH2或敲减lncRNA NEAT1对细胞增殖、迁移和凋亡能力的影响。结果：生物信息学分析筛选获得EZH2上游miRNA和lncRNA为has-miR-450b-5p和lncRNA NEAT1，双荧光素酶报告基因实验验证了两者间存在靶向关系。lncRNA NEAT1和EZH2 mRNA、蛋白在胃癌细胞中均呈高表达（均P<0.05）。与mimic-NC组相比，hsa-miR-450b-5p-mimic组MGC-803、SGC-7901细胞中miR-450b-5p水平均显著升高，而EZH2 mRNA、蛋白和lncRNA NEAT1的表达量均显著降低（P<0.05或P<0.01）；与si-NC组相比，si-NEAT1组MGC-803、SGC-7901细胞中lncRNA NEAT1和EZH2 mRNA的表达量均显著降低（均P<0.01），SGC-7901细胞中hsa-miR-450b-5p表达量显著升高（P<0.05）。敲减EZH2或敲减lncRNA NEAT1后，MGC-803、SGC-7901细胞的增殖、迁移能力均显著降低（均P<0.01）。结论：lncRNA NEAT1 和EZH2在胃癌细胞中均呈高表达，lncRNA NEAT1可通过hsa-miR-450b-5p促进EZH2的表达并提高胃癌MGC-803和SGC-7901细胞的增殖和迁移能力。

ObjectiveTo prepare a rat model of heart failure after myocardial infarction by ligation of the anterior descending branch of the left coronary artery， and to observe the effect of Shenfu Yixin granules on the mitochondrial dynamics of rats with heart failure. MethodFifty SD male rats were randomly taken ten as the sham operation group and the rest as modeling group. The rat model of heart failure after myocardial infarction was prepared by ligation of anterior descending branch of left coronary artery. According to the left ventricular ejection fraction（LVEF） on the 28^th day after operation， the model rats were randomly divided into the model group， Shenfu Yixin granule low-dose and high-dose groups（3.011， 15.055 g·kg^-1） and sacubitril valsartan sodium group（20.83 mg·kg^-1）. Each administration group was gavaged daily with the corresponding dose of drug solution， while the sham operation group and model group were given the same amount of normal saline once a day for 28 days， with 6 rats in each group. Ultrasound was used to detect the cardiac function parameters， rat heart mass and body mass were weighed to calculate the cardiac mass index， enzyme linked immunosorbent assay（ELISA） was used to detect serum brain natriuretic peptide（BNP） and soluble growth stimulation expressed gene 2 protein（sST2） levels. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of the myocardium. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the mRNA and protein expression of mitochondrial fusion protein 1/2（Mfn1/2）， optic atrophy protein 1（Opa1）， dynamin-related protein 1（Drp1） and fission protein 1（Fis1）. ResultCompared with the sham operation group， the mRNA and protein expression of LVEF， Mfn1， Mfn2， Opal in the model group decreased（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels increased（P<0.05）. Compared with the model group， the expression of LVEF， Mfn1， Mfn2， Opal mRNA and protein increased in Shenfu Yixin granule high-dose and sacubitril valsartan sodium groups（P<0.05）， while BNP， sST2， cardiac mass index， Drp1， Fis1 mRNA and protein levels decreased（P<0.05）. Pathological observation showed that compared with the sham operation group， the model group had disordered arrangement of myocardial cells， inflammatory cell infiltration and myocardial fibrosis. Compared with the model group， the degree of inflammatory cell infiltration， myocardial or interstitial fibrosis was improved and alleviated in all administered groups. ConclusionShenfu Yixin granules can resist heart failure， reduce cardiac mass index， decrease BNP and sST2 contents， and improve cardiac function. Its mechanism may be related to the adjustment of mitochondrial dynamics.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

AIM: To analyze the correlation between ocular surface status and serum lipids in patients with meibomian gland dysfunction(MGD)during pregnancy, and to provide new ideas for the management and treatment of MGD during pregnancy.METHODS: Totally 120 pregnant women(240 eyes)treated in our hospital from May 2021 to May 2022 were selected and they were divided into MGD group(60 cases, 120 eyes)and control group(60 cases, 120 eyes)according to the presence or absence of MGD. All subjects received the ocular surface disease index scores(OSDI)and underwent examinations of meibomian gland morphology and function, tear film and blood lipid.RESULTS: The scores of OSDI, the related indexes of meibomian gland, corneal fluorescein staining(FL)scores, total cholesterol(TC), triglyceride(TG)and low density lipoprotein-cholesterol(LDL-C)in the MGD group were significantly higher than those in the control group(P<0.05). The scores of fluorescein breakup time(FBUT), Schirmer Ⅰ test(SIt)and high-density lipoprotein cholesterol(HDL-C)in the MGD group were significantly lower than those in the control group(P<0.05). Correlation analysis showed that the scores of TG, TC, LDL-C were negatively correlated with the values of FBUT(rs =-0.702, -0.647, -0.710, all P<0.001).CONCLUSION: The level of blood lipids in pregnant patients with MGD is significantly increased, and the levels of TC, TG and LDL-C may be related to the stability of tear film.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.

Objective:To investigate the current situation and influencing factors of the cognition of self-supporting for the elderly in nursing institutions, in order to provide a reference basis for constructing an intervention system of self-supporting in nursing institutions and implementing self-supporting more effectively.Methods:This study was a cross-sectional study. From April to August 2023, 320 elderly people from 7 elderly care institutions in Changsha City were selected by convenience sampling method, and the general information questionnaire, the Barthel Index Scale, the Comprehension Social Support Scale, and the self-developed questionnaire on knowledge belief, and practice of self-supporting for the elderly in nursing institutions were used to investigate. Multiple linear regression was used to analyze the factors influencing self-supporting for older people in nursing facilities.Results:Totally 315 valid questionnaires were recovered including 95 males and 220 females, with the majority aged 80-89 years, being 159. The surveyed elderly people in nursing institutions scored (91.24 ± 11.92) points on the self-supporting knowledge questionnaire, and the mean score of the entries was (3.51 ± 0.46) points. The results of multiple linear regression showed that the total scores of activity frequency, the Barthel index of activities daily living and perceived social support were the main factors affecting self-supporting ( t = 5.02, - 6.67, 9.48, all P<0.05), which could explain 51.8% of the total variation. Conclusions:The self-supporting of the elderly in nursing institutions is at a high level, and relevant personnel can better exert the subjective initiative of the elderly in nursing institutions by publicizing and educating the elderly on self-supporting, organizing regular activities and strengthening social support construction.

OBJECTIVES: To construct a quantitative index system with the integrated medical and nursing care assessment for the elderly service needs, this system can assess the cost of medical and care services accurately and objectively, so as to provide scientific basis for the allocation of old-age service resources in China. METHODS: Based on the survival needs of the Existence, Relation and Growth theory, an index system is constructed through literature analysis, group discussion, and expert correspondence. Analytic hierarchy process was used to determine the weights of indicators at all levels. The 3-grades service items corresponding to each index were quantified through the measurement of working hours, and the medical and nursing care needs of 624 disabled/demented elderly people over 60 years old in Changsha were investigated to evaluate their reliability and validity. RESULTS: The authoritative coefficients of the 2 rounds of expert correspondence were 88.5% and 88.6%, respectively, and the opinion coordination coefficients were 0.159 and 0.167, respectively. The final quantitative evaluation index system included 4 first-level indicators, 17 second-level indicators, and 105 third-level indicators. The service time of doctor ranged from 6.01 to 22.64 min, the service time of nurses ranged from 0.77 to 24.79 min, and the service time of caregiver ranged from 0.12 to 51.88 min. The Cronbach's αcoefficient was 0.73, the split-half reliability was 0.74, the content validity was 0.93, and the calibration validity was 0.781. CONCLUSIONS The quantitative evaluation index system of medical and nursing service need for the elderly can be used to accurately evaluate the medical and nursing service need.
Humans ; Aged ; Middle Aged ; Reproducibility of Results ; Surveys and Questionnaires ; Delphi Technique ; Nursing Care ; China

Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.