Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

Objective:To investigate the role of miR-144-3p in cisplatin resistance of bladder cancer.Methods:Bladder cancer T24 cells were cultured in vitro and divided into blank group (untreated), mimetic control group, miR-144-3p mimetic transfection group, inhibitor control group, and miR-144-3p inhibitor transfection group. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to verify the transfection effect, methyl thiazolyl tetrazolium (MTT) method was used to detect the survival rate of cells treated with cisplatin in each group, and Western blot was used to detect the expression of the target protein. The targeting relationship between miR-144-3p and nuclear factor E2 related factor 2 (Nrf2) was validated using dual fluorescence reporter gene experiments. Furthermore, Nrf2 was knocked out in each group of cells, and the mRNA and protein expression levels of HO-1, Bcl-2, and Caspase-3 were detected by qRT-PCR and Western blot in each group of cells.Results:Compared with the control group, bladder cancer cells in the miR-144-3p mimetic transfection group were more sensitive to cisplatin, while the miR-144-3p inhibitor transfection group had the opposite effect; The miR-144-3p simulant transfection group can effectively inhibit the mRNA and protein expression level of Nrf2 in bladder cancer cells (all P<0.05), while the miR-144-3p inhibitor transfection group can up regulate the mRNA and protein level of Nrf2 (all P<0.05). The miR-144-3p mimetic transfection group showed significant downregulation of mRNA and protein expression of HO-1 and Bcl-2, while the expression of Caspase-3 was upregulated (all P<0.05), while the miR-144-3p inhibitor transfection group showed the opposite results. The luciferase results confirmed that miR 144 3p can directly bind to the 3′- UTR region of Nrf2, reducing the mRNA level of Nrf2. When Nrf2 was knocked out, whether miR-144-3p mimetic transfection group or miR-144-3p inhibitor transfection group, the mRNA and protein expression levels of HO-1, Bcl-2 and Caspase-3 did not change significantly, and miR-144-3p lost the ability to regulate the cisplatin sensitivity of bladder cancer cells. Conclusions:miR-144-3p targets to regulate the sensitivity of Nrf2 to cisplatin in bladder cancer, and miR-144-3p is expected to become a new target for the treatment of cisplatin resistant or refractory bladder cancer.

Objective:To investigate the additional value of unenhanced computed tomography (CT) in the differential diagnosis of brain tumors and non-neoplastic lesions.Methods:A total of 237 cases [140 males and 97 females; (49±16) years old; including 48 cases of low-grade glioma, 134 cases of high-grade glioma, 38 cases of primary central nervous system lymphoma, 9 cases of medulloblastoma, 5 cases of germinoma, and 3 cases of central neurocytoma] of brain tumors (diffuse gliomas and non-glial tumors) diagnosed by biopsy or surgery and pathology in the Affiliated Hospital of Qingdao University from September 2016 to October 2020 were collected retrospectively. Sixty-six cases [46 males and 20 females; (42±13) years old; including 12 cases of abscesses, 5 cases of infarcts, 33 cases of demyelinating lesions, 11 cases of autoimmune encephalitis, and 5 cases of central nervous system vasculitis] of brain non-neoplastic lesions were confirmed by biopsy or clinic. All patients underwent routine magnetic resonance imaging (MRI) scan and unenhanced CT before the treatment. The images were reviewed by two neuroradiologists together blind to the final diagnosis with and without CT images respectively. The diagnostic results and reliability scores were recorded, and the accuracy of the two evaluations was compared.Results:CT hyperattenuation exhibited a higher specificity (95%) than conventional MRI scan (86%), and a lower diagnostic sensitivity (34% vs 86%). Compared to MRI alone, the combined modality of MRI and unenhanced CT significantly improved diagnostic accuracy (94% vs 86%). Additionally, the CT attenuation ratio of non-neoplastic lesions was significantly lower than that of neoplastic lesions [0.69 (0.61,0.78) and 1.14 (1.00,1.25), W=2 123, P<0.05]. The CT attenuation ratio in the non-glial origin tumor group was significantly higher than that in the diffuse glioma group [1.28 (1.18,1.41) and 1.13 (0.97,1.21), W=1 858, P<0.05]. There was no significant difference in grade Ⅲ and Ⅳ groups of diffuse glioma [1.11 (0.99,1.20) vs 1.16 (1.09,1.24), P>0.05 (Nemenyi test)]. However, both were significantly higher than that of grade Ⅱgroup of diffuse glioma [0.89 (0.76,1.07), P<0.05 (Nemenyi test)]. No significant difference was observed between astrocytic tumors and oligodendroglial tumors at the same grade. Conclusions:Hyperattenuation on unenhanced CT is highly specific for the diagnosis of brain tumors. Unenhanced CT plus MRI is more accurate for distinguishing the two entities in hypoattenuation lesion on unenhanced CT.

Objective:To explore the new generation of intelligent ICU Unit based on 5G and artificial intelligence technology.Methods:This study was conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine from May 2019 to August 2020. Based on a multidisciplinary team including medical, nursing, hospital management, clinical medical engineering, 5G technology, information technology, artificial intelligence technology, logistics service, etc, was assembled to intelligently design and reconstruct an intelligent ICU Unit of Emergency ICU.Results:Based on 5G technology, a new intelligent ICU unit environment was constructed to realize remote and high-speed interaction of multi-dimensional information in ICU, including intelligent assistance of remote monitoring, remote ward rounds, remote consultation and family visits. An intelligent hospital infection prevention and control system was established including automatic identification and alarm of hand hygiene and personal protection.Conclusions:The new generation of intelligent ICU unit combined with 5G and artificial intelligence technology has changed the mode of medical service for critically ill patients and improved the service level, which is worthy of further exploration and application.

Objective:To evaluate a new type of draw-bar skin stretcher in repair of full-thickness skin defects.Methods:From May 2015 to January 2019, 52 patients with full-thickness skin defects were repaired with a new type of draw-bar skin stretcher at Daping Hospital, Army Medical University. They were 40 males and 12 females, aged from 4 to 61 years (average, 37.1 years). Their skin was stretched for primary wound closure. When primary wound closure failed, skin stretching was performed again to close the wound depending on the wound condition. When the Pinch test was negative after skin stretching, the wound was sutured directly. In cases of positive Pinch test, a skin graft or flap was used to repair the remaining wound. At 12 months after surgery, scar contracture and size of skin graft or flap were observed and wound healing after skin stretching was evaluated in comparison with the original wound.Results:After skin stretching, one-stage wound closure was achieved in 36 cases and multi-stage wound closure in 8 cases; of the remaining 8 cases, 2 were repaired by skin graft and 6 by skin flap after their wounds were reduced by skin stretching. In one-stage closed wounds, infection occurred in 3 cases and marginal necrosis in 5 cases; in the wounds repaired by skin graft or flap, no infection or necrosis was observed. The 12-month follow-up for all the patients showed fine healing of all the wounds after one-stage or multi-stage closure, linear scar, absence of scar contracture, and smaller wound sizes than the original ones after skin graft or flap repair.Conclusions:Skin stretching using our new type of draw-bar skin stretcher is an effective treatment for skin wounds. It can replace traditional skin grafting and flap surgery in some cases, but its indications should be strictly followed to avoid related complications.

Objective:To determine the expression of microRNA-188-5p (miR-188-5p) in cutaneous squamous cell carcinoma (CSCC) tissues and cells, and to assess the effect of its downregulation on the proliferation and invasion of CSCC cells.Methods:From November 2012 to October 2018, 50 surgically resected CSCC tissue specimens and 50 paracancerous normal skin tissue specimens were collected from the First Affiliated Hospital of Xinxiang Medical College in Henan Province. Real-time fluorescence-based quantitative PCR (qPCR) was employed to determine the expression of miR-188-5p in CSCC tissues, paracancerous normal skin tissues, CSCC cell lines SCL-1, A431 and HSC-5, and a human immortalized keratinocyte line HaCaT. Cultured A431 and HSC-5 cells were both divided into 2 groups: miR-188-5p inhibitor group and negative control group, which were transfected with a miR-188-5p inhibitor and its negative control respectively. Then, qPCR was performed to determine the relative expression level of miR-188-5p (expressed as 2 -△△Ct), and cell counting kit-8 (CCK8) and Transwell assays were conducted to assess cellular proliferative activity and invasive ability respectively in the above groups. Dual-luciferase reporter assay was performed to investigate interactions between miR-188-5p and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and Western blot analysis to determine the protein expression of PTEN, total Akt (t-Akt) and phosphorylated Akt (p-Akt). Two independent samples were compared by using t test. Results:The relative expression level of miR-188-5p was significantly higher in the CSCC tissues (5.213 ± 3.138) than in the paracancerous normal skin tissues (1.010 ± 0.364, t = 9.187, P < 0.001), and significantly higher in the SCL-1, A431 and HSC-5 cells (3.858 ± 0.163, 7.068 ± 0.262 and 4.572 ± 0.413, respectively) than in the HaCaT cells (1.079 ± 0.300, t = 17.890, 21.110 and 8.737, respectively, all P < 0.05). Compared with the negative control group, the miR-188-5p inhibitor group showed significantly decreased miR-188-5p expression in both A431 and HSC-5 cells (both P < 0.01), and decreased proliferative activity and invasive ability of both A431 and HSC-5 cells (all P < 0.05). Dual-luciferase reporter assay showed that the downregulation of miR-188-5p significantly increased the expression of PTEN, but inhibited the expression of p-Akt in A431 and HSC-5 cells. Conclusion:MiR-188-5p is highly expressed in CSCC tissues and cells, and the downregulation of miR-188-5p may inhibit the proliferative activity and invasive ability of CSCC cells by regulating the PTEN/Akt pathway.

Salinity is the most important factor for the growth of crops. It is an effective method to alleviate the toxic effect caused by salt stress using saline-alkali-tolerant and growth-promoting bacteria in agriculture. Seven salt-tolerant bacteria were screened from saline-alkali soil, and the abilities of EPS production, alkalinity reduction and IAA production of the selected strains were investigated. A dominant strain DB01 was evaluated. The abilities of EPS production, alkalinity reduction and IAA production of strain DB01 were 0.21 g/g, 8.7% and 8.97 mg/L, respectively. The isolate was identified as Halomonas aquamarina by partial sequencing analysis of its 16S rRNA genes, and had the ability to inhibit the growth of Fusarium oxysporum f. sp., Alternaria solani, Phytophthora sojae and Rhizoctonia cerealis. It also could promote root length and germination rate of wheat seedlings under salt stress. Halomonas aquamarina can provide theoretical basis for the development of soil microbial resources and the application in saline-alkali soil improvement.
Alkalies ; metabolism ; Bacteria ; drug effects ; genetics ; Halomonas ; genetics ; Plant Roots ; microbiology ; RNA, Ribosomal, 16S ; genetics ; Salt Tolerance ; genetics ; Seedlings ; growth & development ; microbiology ; Soil ; chemistry ; Soil Microbiology ; Triticum ; microbiology

Objective:To analyze the mutation sites and characteristics of phospholipase CE1( PLCE1) gene in children with primary nephrotic syndrome(PNS) in Zhuang, Guangxi, China, so as to explore the expression status of PLCE1 protein in peripheral blood of PNS patients. Methods:(1)Blood samples of 154 Zhuang children with PNS and 98 healthy children of Zhuang nationality from July 2015 to September 2017 in Affiliated Hospital of Youjiang Medical College for Nationalities were collected to sequence PLCE1 gene with FastTarget target gene capture method in the combination with next generation sequencing.Based on the comparison between mutation results and information from the database, the pathogenicity, phenotype and distribution characteristics of these mutation sites were discovered and appraised.(2)The concentration of PLCE1 protein in serum samples were measured by enzyme-linked immuno sorbent assay, then the data of PNS group and healthy control group were compared and analyzed statistically with SPSS 25.0. Results:(1)A total of 18 low-frequency mutations of PLCE1 were observed, 5 of them(c.670C>T, c.578T>C, c.923G>T, c.4916C>T, and c. 5927_5929del) were found only in the PNS group, and 3 of them occurred in both PNS group and healthy control group: c.176C>T, c.389T>C, and c. 4304C>T.Five newly discovered mutations (c.923G>T, c.958T>A, c.1151C>T, c.2341A>G, and c. 3592G>C)were discovered and only c. 923 G>T is pathogenic mutation of PLCE1.(2)The concentration of PLCE1 protein in healthy control group was 414.65 (231.20, 729.81) ng/L and the level of PLCE1 in PNS group was 237.84 (116.14, 535.85) ng/L, ( Z=-3.212, P<0.001), and the value of PNS group was lower than that in the healthy control group. Conclusions:(1)As a new pathogenic mutation of PLCE1, c.923G>T was found.(2)The phenotype of PLCE1 gene mutation in Zhuang children with PNS was diverse, and they may differ by race and region.(3) PLCE1 protein of serum may act as a protective protein to guarantee various life activities of cells by participating in multiple signal transduction pathways.

Objective To evaluate the effect of downregulation of microRNA (miR)-373 expression on cell cycle and apoptosis of a cutaneous squamous cell carcinoma (CSCC) cell line A431.Methods A431 cells at exponential growth phase were classified into 3 groups:miR-373 inhibitor group and negative control group transfected with miR-373 inhibitor and negative control miRNA respectively,and untreated group receiving no treatment.At 48 hours after the transfection,real-time PCR was performed to determine the expression of miR-373 in the above 3 groups,cell counting kit-8 (CCK-8) assay to evaluate the effect of downregulated expression of miR-373 on the proliferation of A431 cells,flow cytometry to investigate the distribution of cell cycle and changes in apoptosis of A431 cells in different treatment groups,and colorimetric analysis to detect the changes in caspase-3 activity in different treatment groups.Statistical analysis was carried out with SPSS 17.0 software by using two-sample t test for the comparison between two groups,one-way analysis of variance (ANOVA) for the comparison among 3 groups,and least significant difference (LSD)-t test for multiple comparisons.Results The expression of miR-373 was significantly lower in the miR-373 inhibitor group (0.120 ± 0.036) than in the untreated group (1.002 ± 0.022) and negative control group (1.037 ± 0.028,LSD-t =36.21,34.83,respectively,both P ＜ 0.001).At 48,72 and 96 hours,the miR-373 inhibitor group showed significantly decreased proliferative activity of A375 cells compared with the untreated group and negative control group (F =10.805,13.720 and 30.907 respectively,P =0.038,0.010 and 0.001 respectively).The proportion of A375 cells in G0/G1 phase was significantly higher in the miR-373 inhibitor group (64.69％ ± 1.18％) than in the untreated group (52.74％ ± 0.66％,t =15.51,P ＜ 0.001) and negative control group (53.80％ ± 0.80％,t =13.24,P ＜ 0.001).The proportion of total apoptotic cells and activity of caspase-3 in the miR-373 inhibitor group were 22.69％ ± 1.24％ and 1.238 ± 0.057 respectively,which were significantly higher than those in the untreated group (9.62％ ± 1.14％,0.413 ± 0.028 respectively,both P ＜ 0.001)and negative control group (9.66％ ± 0.97％,0.437 ± 0.036 respectively,both P ＜ 0.001).Conclusion MiR-373 may play an important role in the regulation of cell cycle and induction of apoptosis of the CSCC cell line A431.

Objective: To investigate the effect of papaverine on wound healing of full-thickness skin defect after skin stretching in swine. Methods: Eight Bama pigs were prepared. Standard full-thickness skin defect for 7 cm×7 cm was produced in the middle part of each pig's forelimb, and skin traction was used to close the wound. According to random number table method, the pigs were divided into experiment group and control group, with four pigs in each group. Percutaneous oxygen partial pressure (TcPO₂) was compared preoperatively and postoperatively. Wound healing clinical score was evaluated four and 10 days after operation. Weidner counting method was employed to determine the microvascular density (MVD) of the wound edge tissue 0 and 10 days after operation. Immunohistochemistry was used to observe the expression of hypoxia inducible factor 1-α (HIF- 1α) and vascular endothelial growth factor (VEGF) 0, 4 and 10 days after operation. Results: There was no statistically significant difference in TcPO₂ between the experiment group [(55.1±5.4)mmHg] and the control group [(54.7±5.9)mmHg] before skin stretching (P>0.05), while statistically significant difference was found after stretching [(22.7±3.3)mmHg vs. (16.4±3.4)mmHg] (P<0.01). There was no statistically significant difference in clinical wound healing scores between the control group and experiment group 4 days after skin stretching [(2.6±0.7)points vs. (2.1±0.4)points] (P>0.05), but better result was found in experiment group compared with the control group in 10 days [(1.3±0.5)points vs. (4.6±0.7)points] (P<0.01). MVD of skin tissue showed no statistically significant difference between the control group (8.5±1.3) and the experiment group (9.3±1.2) immediately after skin stretching (P>0.05), while the MVD of wound skin tissue in the experiment group (29.5±4.8) was significantly higher than that in the control group (21.1±3.4) 10 days after skin stretching (P<0.01). After skin stretching, the HIF-1 alpha expression in experiment group was significantly higher than the control group 4 days after skin stretching [(50.0±7.0) vs. (38.6±7.0)] (P<0.01), but no statistical significance was found between that at 0 day and 10 days(P>0.05). The expression of VEGF in the wound skin tissues of the experiment group was significantly higher than that of the control group [(49.9±10.8) vs. (39.2±6.3)] at 4 days after skin stretching (P<0.05), while no statistically significance was found at 0 and 10 days (P>0.05). Conclusion For full-thickness skin defect after skin stretching in pigs, papaverine can alleviate small vessel spasm, improve skin edge oxygen supply, and promote the growth of microvessels, thus promoting the healing, which might be associated with the increase of HIF-1ɑ and VEGF expression.