Objective:To explore the role and mechanism of kidney brain protein (KIBRA) down-regulation in cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Ninety male SPF grade Sprague Dawley (SD) rats were divided into four groups according to random number table: sham operation group ( n=15), chronic hypoperfusion group (2VO group, n=25), chronic hypoperfusion stereotaxic injection of AAV-KIBRA group (2VO+ AAV-KIBRA group, n=25), chronic hypoperfusion stereotaxic injection of AAV-Vector group (2VO+ AAV-vector group, n=25). Chronic cerebral hypoperfusion model was established by bilateral ligation of common carotid artery, and stereotactic injection of 2 μL AAV-KIBRA or AAV-vector was performed for 30 days.Morris water maze, in vitro electrophysiology, p21-activated kinase 3(PAK3) activity detection, Western blot, immunoprecipitation and Golgi staining were used to detect spatial learning and memory ability, long-term potentiation(LTP), KIBRA level expression, PAK3 activity changes and the distribution of dendritic spines.SPSS 16.0 statistical software was used for statistical data.One-way ANOVA was used to compare the differences between groups.LSD test was used to compare the significance of data differences between the two groups.Welch test was used for uneven variance. Results:After 1 month of chronic cerebral hypoperfusion, the level of KIBRA in the hippocampus of rats was detected by homogenate and Western blot, and it was found that the level of KIBRA in 2VO group was lower than that of sham group(73.49±4.12)% ( P<0.01). AAV-KIBRA injection in hippocampal CA1 region significantly up-regulated the level of KIBRA to (91.91±7.01)% over 2VO group ( P<0.01). Morris water maze test showed that the latency of the 2VO group(3rd-7th day trail data: (48.18±2.82)s, (43.45±2.27)s, (32.27±2.22)s, (26.55±2.37)s, (17.18±2.67)s) were significantly longer than those of the sham group((41.67±2.74)s, (32.58±2.57)s, (22.50±2.94)s, (16.91±2.39)s, (8.75±1.52)s) (all P<0.05), and the latencies of the 2VO+ AAV-KIBRA group 3rd-7th day trail data: (43.83±2.95)s, (35.25±2.15)s, (26.58±2.03)s, (19.92±2.17)s, (17.75±1.35)s) was significantly shorter than that of the 2VO group ((all P<0.01). The Morris water maze test with the platform removed showed that the latency of rats in the 2VO group to reach the platform region was significantly longer than that of the sham group, while the latency of rats in the 2VO+ AAV-KIBRA group to reach the platform region was significantly shorter than that in the 2VO group ( P<0.01). At the same time, the retention time and the crossing times in the platform region of 2VO group were less than those of the sham group ( P<0.01), but the retention time and the crossing times in the platform region of 2VO+ AAV-KIBRA group were significantly higher than those in the 2VO group ( P<0.01). The electrophysiological records of the brain slices showed that the relative excitatory postsynaptic field potential of 2VO group (1.43±7.43) was significantly lower than that of sham group (2.21±6.54) after high frequency stimulation, while the relative excitatory postsynaptic field potential of 2VO+ AAV-KIBRA group (1.90±8.15) was higher than that of 2VO group ( P<0.01). Immunoprecipitation in rat hippocampus revealed that PAK3 could be detected by Western blot assay when KIBRA was precipitated.The results showed that the relative enzyme activity of PAK3 in 2VO hippocampal tissue (0.64±0.04) was significantly lower than that in sham group (1.02±0.07), while the relative enzyme activity of PAK3 in 2VO+ AAV-KIBRA group (0.86±0.03) was significantly higher than that in 2VO group.Golgi staining showed that the density of dendritic spines in 2VO hippocampal neurons((6.85±0.43)/10 μm) was significantly lower than that in sham group((11.83±0.58)/10 μm), while the density of dendritic spines in 2VO+ AAV-KIBRA group((10.22±0.39)/10 μm) was significantly higher than that in 2VO group. Conclusion:The down-regulated of KIBRA after chronic cerebral hypoperfusion plays a key role in cognitive dysfunction and is also involved in the decrease of synaptic functional plasticity.The downregulation of KIBRA is involved in the structural plasticity of dendrites through the regulation of PAK3 activity.Therefore, KIBRA may be an important target for the prevention and treatment of cognitive function of chronic cerebral hypoperfusion.

Objective:To investigate the clinical manifestation, diagnosis and treatment of chronic lymphocytic leukemia patients with renal involvement.Methods:The clinical data of a chronic lymphocytic leukemia patient with nephrotic syndrome as the initial manifestation in Fujian Provincial People's Hospital in October 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 68-year-old male with recurrent edema and foam urine as the initial manifestations, and he was diagnosed as nephrotic syndrome in the nephrology department. After treatment, the symptoms showed no significant improvement, and the lymphocyte count gradually increased. The patient was diagnosed as chronic lymphocytic leukemia in the hematology department. After ibrutinib monotherapy, the lymphocyte count and urine protein gradually decreased to normal levels, and the clinical efficacy evaluation of the patient was complete remission at the end of follow-up.Conclusions:Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation is rare, and the clinical presentations are variable. Early diagnosis is the guarantee of successful treatment. The efficacy and safety of first-line Bruton tyrosine kinase inhibitor monotherapy are good.

Using novel virtual reality (VR) technology to carry out the construction of clinical medical examination question bank, while deepening the reform of clinical medical course examination, it continues to innovate the medical professional evaluation system and improve the flexibility, diversity and scientificity of clinical medicine in teaching and assessment. It is of great and far-reaching significance to improve the teaching level and the quality of medical education in medical colleges and universities. This paper analyzes and discusses the necessity and feasibility of building a clinical medical examination question bank, and the advantages and prospects of integrating VR technology to carry out the construction of clinical medical examination question bank. At the same time, the exploration and practice of the examination question bank construction based on VR technology disscussed in detail would provide innovative thinking and reference for the clinical medical teaching and evaluation, medical personnel training and other aspects in China.

Myosin light chain 9 (MYL9) is a regulatory light chain of myosin, which plays an important role in various biological processes including cell contraction, proliferation and invasion. MYL9 expresses abnormally in several malignancies including lung cancer, breast cancer, prostate cancer, malignant melanoma and others, which is closely related to the poor prognosis, but the clinical significance for its expression varies with different types of cancer tissues. Further elucidating the molecular mechanism of MYL9 in various types of malignant tumor metastasis is of great significance for cancer prevention and treatment. At the same time, as a molecular marker and potential target, MYL9 may have great clinical value in the early diagnosis, prognosis prediction, and targeted treatment of malignant tumors.
Biomarkers ; Humans ; Lung Neoplasms ; Male ; Myosin Light Chains/metabolism* ; Prognosis ; Prostatic Neoplasms

Virtual reality technology is a technology that creates a visual environment for people to experience through computer simulation, with features of immersion, interaction and imagination. This technology was used in engineering mechanics and urban planning in early times In medicine, diagnostics serves as a bridge for medical students to transit from basic medicine to clinical medicine. Using virtual reality technology to produce standardized patients (SPs) allows medical students to simulate the role of clinicians in the classroom, complete the diagnosis and treatment for virtual patients using various electronic media and the mastered theoretical knowledge of diagnostics, set up simulation training and online-and-offline teaching according to the diagnostic course standards which compensates the disadvantages in traditional medical teaching. Virtual reality technology has practical significances for cultivating medical students' clinical skills and thinking through procedural process evaluation, real-time feedback, etc.. This paper will discuss the prospect of virtual reality technology, its application as well as its advantages in diagnostic teaching.

T-cell acute lymphonlastic leukemia(T-ALL) is one of the common hematological malignancies in children and adolescents, and it has a rapid progress and high mortality.Since the first activated mutation in NOTCH1 was found in T-ALL with t(7; 9) translocation in 1991.The pathogenesis and clinical treatment of NOTCH1 gene mutation and T-ALL had made some progress at subsequent years.However, there are still some differences in the prognosis of children and adults after using chemotherapy drugs.Therefore, the differences of prognosis of acute lymphoblastic leukemia with NOTCH1 gene mutation in adults and children and the latest treatment progress are reviewed and hope to provide guidance for clinical treatment.

Objective:To explore the protective effect and mechanism of diammonium glycyrrhizinate (DAG) on cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Seventy-three male Sprague Dawley rats in SPF degree were divided into sham group, chronic cerebral hypoperfusion group(2VO group), chronic cerebral hypoperfusion with DAG treatment group(2VO+ DAG group), and DAG treatment group(DAG group). During one-month chronic cerebral hypoperfusion models reproduced by the occlusion of bilateral common caroid artery, the rats were injected intraperitoneally with 2.917 mmol/L(20 mg·kg -1·d -1) DAG or saline for 15 days.Then the ability of learning and memory were tested by Morris water maze.Elisa, Western blot and Golgi staining were employed to test the spatial cognition, the changes of inflammatory factors, and inflammatory signal pathway molecules in hippocampus.The distribution of dendritic spines were observed and counted. Results:Morris water maze test showed that the learning latency of rats in 2VO group (3rd -7th day ) ((50.70±2.01)s, (43.53±3.22)s, (35.41±2.13)s, (25.26±1.85)s, (17.92±2.24)s) was significantly longer than that of sham group((40.28±1.94)s, (31.51±3.23)s, (24.7±2.25)s, (13.23±2.51)s, (9.42±1.91)s) (all P<0.01), while that of 2VO+ DAG group ((46.27±1.64)s, (38.54±1.51)s, (28.74±2.52)s, (19.73±2.13)s, (13.26±1.71)s) was significantly shorter than that of 2VO group ( P<0.05, P<0.01). After removing the platform to detect the memory of rats, the results showed that the latency of 2VO group (18.56±1.72)s) was significantly longer than that of sham operation group (11.25±2.11)s) ( P<0.01), while the time of 2VO+ DAG group was shorter than that of 2VO group (14.26±1.51)s ( P<0.01). In terms of the time of staying in the platform quadrant, the times of crossing through the platform area, the rats in the 2VO group were significantly less than those in the sham group ( P<0.01), while the rats in the 2VO+ DAG group were significantly more than those in the 2VO group ( P<0.01). Elisa data showed the levels of TNF-α, IL-1β and IL-6 in 2VO group (TNF-α: (27.42±1.91) pg/mg; IL-1β: (18.21±1.56)pg/mg; IL-6: (17.94±1.61)pg/mg)) were higher than those in sham group (TNF-α: (8.11±1.27)pg/mg; IL-1β: (6.78±1.12)pg/mg; IL-6: (5.67±0.91)pg/mg)) ( P<0.01), while the levels of three inflammatory factors in 2VO+ DAG group (TNF-α: (12.25±2.38)pg/mg; IL-1β: (9.93±0.96)pg/mg; IL-6: (8.72±0.65)pg/mg)) were significantly lower than those in 2VO group ( P<0.01). Western blotting data showed that the relative level of NF-κB in the nucleus of 2VO group (1.82±0.15) was significantly higher than that of sham group (1.00±0.09)( P<0.01), while that of 2VO+ DAG group (1.42±0.10) was significantly lower than that of 2VO group ( P<0.01). Golgi staining showed that the density of dendritic spines in CA1 area of hippocampus in 2VO group ((5.00±1.41)/10 μm) was significantly lower than that in sham group ((12.86±1.12)/10 μm) ( P<0.01), while that in 2VO+ DAG group was significantly higher than that in 2VO group ((9.23±1.65)/10 μm) ( P<0.01). Conclusion:DAG can effectively inhibit the neuroinflammatory response of hippocampus in chronic cerebral hypoperfusion, improve the damage of synaptic plasticity, and then improve the cognitive dysfunction caused by chronic hypoperfusion.DAG may be a potential effective drug for the treatment of chronic cerebral ischemia and vascular dementia.

Objective:To explore the clinical effect of R-MAD (rituximab, methotrexate, cytarabine, dexamethasone) regimen in the treatment of primary ocular adnexal double-expression diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of an elderly patient with primary ocular adnexal double-expression DLBCL who was treated with R-MAD regimen in June 2019 in Fujian Medical University Union Hospital was retrospectively analyzed. The clinical manifestations, diagnosis and treatment, prognosis were also analyzed, and the related literature was reviewed.Results:The patients was a 71-year-old male. After initial treatment of R-CHOP chemotherapy, the patient's eye mass did not shrink, the swelling and pain became worse, the curative effect was not good, and the disease progression continued. After the patient was given R-MAD chemotherapy for 3 courses, the eye swelling subsided and pain symptoms were significantly improved, satisfactory results were obtained, and no obvious adverse reactions occurred.Conclusions:R-MAD regimen has an ideal effect on the patient with primary ocular adnexal double-expression DLBCL, which can significantly improve symptoms, delay disease progression, and improve the quality of life of patients, but the prognosis still needs to be followed up in the long-term.

Objective:To explore the clinical characteristics, diagnosis, treatment and prognosis of patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).Methods:The main clinical manifestations, auxiliary examination results, diagnosis and treatment process, and follow-up data of 5 patients with POEMS syndrome in Fujian Medical University Union Hospital from April 2017 to November 2018 were retrospectively analyzed, and the features of diagnosis and treatment were discussed with review of literature.Results:The patients with POEMS syndrome had typical manifestations of polyneuropathy (5 cases), organomegaly (4 cases), increased extravascular volume load (4 cases), endocrine changes (5 cases), etc. The patients were also accompanied by clinical manifestations of skin changes (2 cases), bone damage (3 cases), kidney damage (2 cases), anemia (4 cases), etc. Three cases were misdiagnosed as chronic Guillain-Barré syndrome. Five patients were followed up regularly, with a median follow-up time of 16 months (13-33 months). Until the end of follow-up, 1 patient who received DVD regimen chemotherapy had a disease-free survival time of 22 months and a survival time of 24 months; 1 patient underwent autologous hematopoietic stem cell transplantation after receiving pretreatment of melphalan scheme, and the survival time was 6 months; the remaining 3 patients were in the disease-free survival period, and among which 1 patient survived 9 months without disease after autologous hematopoietic stem cell transplantation, 1 patient survived 16 months without disease, and 1 patient survived 18 months without disease.Conclusions:The onset of POEMS syndrome is insidious, its clinical manifestations are complex, and it is easy to be misdiagnosed or missed. Clinicians should strengthen their understanding of this disease.

Objective:To analyze the clinical efficacy and safety of decitabine combined with CAG regimen in treatment of elderly patients with acute myeloid leukemia (AML).Methods:Decitabine combined with CAG regimen (experimental group) and CAG regimen alone (control group) were used to treat elderly patients with AML. The randomized controlled trials (RCT) were retrieved from PubMed database, Cochrane Library, Embase database, China Notional Knowledge Infrastructure (CNKI), Wanfang database and VIP database and references listed in all studies. The data of RCT that met the inclusion criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then Meta-analysis was conducted by using StataMP 14.0 software.Results:A total of 16 studies and 1 090 patients were included. Compared with the control group, the experimental group had a higher complete remission rate and total effective rate, and the differences were statistically significant ( RR=1.63, 95% CI 1.40-1.89, P < 0.01; RR=1.39, 95% CI 1.27-1.51, P < 0.01). In terms of adverse reactions, the incidence of fever in the experimental group was higher than that in the control group, and the difference was statistically significant ( RR=2.06, 95% CI 1.54-2.75, P < 0.01). Conclusion:Meta-analysis showed that decitabine combined with CAG regimen has a better clinical efficacy in the treatment of elderly patients with AML, but there are more severe adverse reactions.