Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.

Objective To prepare a sustained-release membrane with longer adhesion time and dissolution time, and compare it with the commercially available oral ulcer membrane. Method Adhesion strength, adhesion time, swelling coefficient, dissolution time, etc. were used as the inspection indicators, and a combination of single factor inspection and analytic hierarchy process were used to screen the membrane -forming materials. The dispersion method of clotrimazole, ornidazole and borneol were investigated to prevent the drug from seed out. The method of combining orthogonal experiment and analytic hierarchy process were used to optimize the dosage of CMC-Na, PVA-1788 and glycerin; and the commercial products were compared. Results Through single-factor investigation and orthogonal experiment, the optimal ratio of excipients was selected as CMC-Na∶PVA-1788∶glycerol (3∶1∶0.08). The water-insoluble component clotrimazole, ornidazole and borneol were treated by precipitation in liquid with good effect. The best method was used to prepare the membrane. The adhesion strength was 102 g. The adhesion time was 55 min. The swelling coefficient was 1 939.52. The average dissolution time was 110 min. The appearance was white and the surface was free of bubbles, soft and elastic. The membrane forming time at 60 ℃ was 300 min and the demolding effect was better which could be completely peeled off with moderate thickness. Conclusion The oral ulcer membrane developed in this method has good appearance, comfortable use, strong adhesion, long adhesion time and dissolution time, and could stay on the ulcer surface for a long time to form physical isolation, and slowly release the drug during the dissolution process, which could play the role of long-term pain relief, antibacterial, anti-inflammatory and promote healing effects on oral ulcers.

Objective:To establish and evaluate a new real-time quality control method that can identify the random errors by using the backpropagation neural network (BPNN) algorithm and taking blood glucose test as an example.Methods:A total of 219 000 blood glucose results measured by Siemens advia 2 400 analytical system from January 2019 to July 2020 and derived from Laboratory Information System of Beijing Chaoyang Hospital Laboratory Department was regarded as the unbiased data of our study. Six deviations with different sizes were introduced to generate the corresponding biased data. With each biased data, BPNN and MovSD algorithms were used and tested, and then evaluated by traceability method and clinical method.Results:For BPNN algorithm, the block size was pre-set to 10 and the false-positive rate in all biases was within 0.1%. For MovSD, however, the optimal block size and exclusive limit were 150 and 10% separately and its false-positive rate in all biases was 0.38%, which was 0.28% higher than BPNN. Especially, for the least two error factors of 0.5 and 1, all the random errors were not detected by MovSD; for the error factor larger than 1, random errors could be detected by MovSD but the MNPed was higher than that of BPNN under all deviations. The difference was up to 91.67 times. 460 000 reference data were produced by traceability procedure. The uncertainty of BPNN algorithm evaluated by these reference data was only 0.078%.Conclusion:A real-time quality control method based on BPNN algorithm was successfully established to identify random errors in analytical phase, which was more efficient than MovSD method and provided a new idea and method for the identification of random errors in clinical practice.

OBJECTIVE：To investigate the effect of increasing efficacy and decreasing toxicity of Limax extract （LE）on cyclophosphamide（CTX）in the treatment of hepatocellular carcinoma. METHODS ：The mice were randomly divided into normal group，model group ，CTX group （0.02 g/kg），LE low-dose ，medium-dose and high-dose groups （LEL，LEM，LEH group ，0.6，1.2，2.4 g/kg），CTX+LE low-dose ，medium-dose and high-dose combination groups （CTX+LEL，CTX+LEM，CTX+ LEH group ，the same dose as single drug group ），with 10 huangrenbin518@163.com mice in each group. Except for normal group ，other groups were inoculated with hepatoma cells H 22 in the left ar mpit to establish tumor bearing models. After 24 h of inoculation ，normal group and model group were intragastrically given normal saline ， and administration groups were intragastrically given corresponding drugs ，once a day ，for 10 days. On the second day after the last administration ，the general conditions of mice in each group were observed ；the body mass ，thymus index （LI），spleen index （SI）were measured ；the tumor inhibition rate was detected. The effect （q）of combination therapy was evaluated by King ’s formula . The counts of WBC ，RBC and PLT ，serum contents of ALT ，ALT，Scr and BUN were detected in model group ，CTX group and combination groups ，and the contents of MDA，SOD and GSH ，the levels of VEGF ，TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above groups. The protein expression of oncogenes （p53，Bcl-2 and Bax ）were detected by immunohistochemical method in model group，CTX group and CTX+LEM group. RESULTS ：The mice in the model group were in poor spirit and had symptoms of excessive drinking and eating ；although the body weight ，TI and SI were not significantly abnormal compared with normal group （P＞0.05），WBC count and AST content were significantly increased ，ALT and BUN contents were significantly decreased （P＜ 0.05 or P＜0.01）. Compared with model group ，above symptoms of mice were all improved in administration groups. The tumor weight of administration groups ，TI and SI of CTX group and TI of combination groups were decreased significantly ，but tumor weight of LEL group and LEH group ，TI and SI of LE single groups and combination groups were significantly higher than CTX group；tumor weight of combination groups were significantly lower than CTX group （P＜0.05 or P＜0.01）. The tumor inhibition rates of administration groups were 29.58％-72.08％. The q values of CTX+LEL group ，CTX+LEM group and CTX+LEH group were 1.03，0.97 and 0.86，respectively. Compared with model group ，WBC count ，AST and BUN contents of CTX group ，MDA contents of combination groups ，VEGF，TNF-α and IL-6 levels of administration groups ，the protein expression of Bcl- 2 in CTX group and CTX+LEM group were decreased significantly ；the activities of SOD and GSH of administration groups ，the protein expression of p 53 in CTX+LEM group and Bax in CTX group ，CTX+LEM group were increased significantly （P＜0.05 or P＜ 0.01）；WBC counts and AST contents of administration groups ，ALT content of CTX+LEM group ，SOD activity of CTX+LEH group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group ；MDA content of CTX+LEH group，VEGF and TNF-α levels of CTX+LEM group and CTX+LEH group，IL-6 levels of administration groups were all significantly lower than CTX group （P＜0.05 or P＜0.01）. CONCLUSIONS ：LE combined with CTX can increase the anti-tumor effect，and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice ，with effect of increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress ，inhibition of angiogenesis and secretion of inflammatory factors ，and regulation of apoptosis protein expression.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

【Objective】 To detect the expressions of microRNA（miR）-362 and histone deacetylase 6 （HDAC6） in bone cancer pain （BCP） rats and investigate the analgesic effect of miR-362 and its potential analgesic mechanism. 【Methods】 The BCP model was developed by injecting Walker 256 mammary gland carcinoma cells into bone marrow cavity. Plasmid transfection was used to regulate the expressions of miR-362 and HDAC6. The Van Frey filaments and radiant heat instrument were used to detect the paw withdrawal threshold （PWT） and paw withdrawal latency （PWL）. qRT-PCR was used to detect mRNA expression levels of miR-362 and HDAC6， and Western blotting was used to detect protein expression of HDAC6 and nuclear factor kappa-B p65 （NF-κB p65）. ELISA assay was used to detect the protein levels of interleukin （IL）-1β， IL-6 and tumor necrosis factor α （TNF-α）. Luciferase activity assay was used to determine the relationship between miR-362 and HDAC6. 【Results】 Compared to sham group， the significant decrease of PWT and PWL， decrease of miR-362 and the increase of HDAC6 mRNA and protein in the spinal were detected in BCP group （P<0.05）. Compared to BCP group， the significantly increase of PWT and PWL and decrease of HDAC6 mRNA and protein in the spinal were detected in BCP+LV-miR-362 group （P<0.05）. Compared to BCP+LV-miR-362 group， PWT and PWL significantly decreased in BCP+LV-miR-362+LV-HDAC6 group （P<0.05）. In addition， compared to BCP group， significant decreases of NF-κB p65， IL-1β， IL-6 and TNF-α in spinal were detected in BCP+LV-HDAC6 siRNA group （P<0.05）. Moreover， compared to mimic miR-362+HDAC6 3’UTR^MUT group， the luciferase activity significantly decreased in mimic miR-362+HDAC6 3’UTR^WT group （P<0.05）. 【Conclusion】 As a key factor regulating the mechanism of BCP through “HDAC6-NF-κB p65” signal pathway in rats， targeting miR-362 may be a novel therapeutic method for BCP.

With this retrospective study, we analyzed the negotiation subject, drug type, drug access mechanism, negotiation link and negotiation result of drug negotiation in typical regions at home and abroad.In foreign countries, drug negotiation mechanism has been implemented for many years, and many countries have established a relatively perfect negotiation system.We selected 8 typical countries and regions for which we statistically analyzed the negotiation subject, drug type, drug access mechanism, negotiation link and negotiation result of drug negotiation and these include the United States, Australia, Canada, France, Germany, Italy, South Korea and Taiwan.However, in recent years some Chinese medical insurance department carried out pilot works on drug negotiations, and they got some successful results of the implementation of practical experience.Eight typical Chinese regions were also selected for statistical analysis, and these include Zhejiang, Hunan, Jiangsu, Jiangxi, Chengdu and Qingdao.From the analysis of the comparison of drug negotiation mechanism in domestic and foreign typical regional, we found that foreign regional drug negotiation mechanism is more mature and perfect, while in the domestic areas the mechanism is still poor at a certain extent as compared to foreign countries.We should learn from the successful experience of foreign countries and also establish and improve the negotiation mechanism that is suitable for China''s national conditions.

Objective:To summarize the evidence for the link between rheumatoid arthritis and risk of vertebral fractures or vertebral deformities with a meta-analysis, so as to provide objective proof for early preventing and the development of vertebral deformity and fractures.Methods:Wanfang,CNKI,VIP,PUBMED,Springlink and Elsevier were retrieved for all publications relating to rheumatoid arthritis and vertebral fractures in women.According to inclusion and exclusion criteria,two investigators collected their data individually,then statistical analysis was performed using Stata 12.0 software.Results: Eight case-control studies were enrolled, including 86 741 participants,2 258 of them with RA.The results of Meta-analysis showed that a higher incidence of vertebral fractures in RA,and Odds ratio was 3.70 with a 95%confidence interval(2.47-5.55,P<0.000 1).The publication bias analysis did not reveal any evidence of obvious asymmetry, and the sensitivity analysis showed that omission of any individual study made no significant difference for all comparison models,suggesting that our results were statistically robust.Conclusion:RA may be one of the risk factors for the vertebral fractures.

This study was aimed to evaluate effects of traditional Chinese medicine ( TCM ) five elements music therapy on the quality of life for both senior and non-senior advanced cancer patients , and improve TCM com-prehensive treatment mode . A total of 170 patients were stratified according to 70-year-old in a randomized controlled trial ( RCT ) with a parallel single-blind design . The ratio of patients among three groups was 2:2:1 . In the experimental group , TCM five elements music was given in the treatment . In the positive control group , western music was used in the treatment . And in the negative control group , no music was given in the treat-ment . The treatment was given for 30 min , 5 times per week . And the observation duration was 3 weeks . The Hospice Quality of Life Index-Revised ( HQOLI-R ) , Karnofsky Performance Scale ( KPS ) and Symptom Diary Score recorded by patients were used in the evaluation . The results showed that when comparing HQOLI-R , KPS and Symptom Diary Score before and after treatment among all advanced cancer patients in each group , there was a significant difference before and after treatment in the TCM five elements music therapy group ( P< 0 . 05 ) . But there was no significant difference before and after treatment in the western music therapy group or the negative control group ( P > 0 . 05 ) . It was concluded that TCM five elements music therapy is effective in improving quality of life and subjective symptoms for both senior and non-senior advanced cancer patients . However , the sensitivity of using the Symptom Diary Score as an evaluation index among senior patients still needs to be further proved .

OBJECTIVETo investigate the role of K(Ca)3.1 channel in the proliferation and migration of rat vascular smooth muscle cells of the proliferative phenotype.

METHODSRat vascular smooth muscle cells (VSMCs) were cultured with tissue adhesion method. The morphological characteristics of the fist and ninth passages of VSMCs were observed with light and electron microscopy and immunocytochemistry. The expressions of K(Ca)3.1 channel mRNA and protein in the cells were detected using RT-PCR and immunocytochemistry, respectively. MTT and transwell assay were employed to assess the effect of the K(Ca)3.1 channel blocker TRAM-34 on the proliferation and migration of VSMCs.

RESULTSThe first and ninth passages of VSMCs showed morphological characteristics of contractile and proliferative phenotypes, respectively. Compared with the first- passage cells, the ninth-passage VSMCs exhibited significantly increased K(Ca)3.1 channel mRNA and protein expressions with enhanced cell proliferation and migration (P<0.01), which was inhibited by the application of TRAM-34 (P<0.01). TRAM-34 produced no obvious effect on the first-passage VSMCs.

CONCLUSIONUpregulated expression of K(Ca)3.1 channel can promote the proliferation and migration of rat VSMCs of the proliferative phenotype.

Animals ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Potassium Channel Blockers ; pharmacology ; Pyrazoles ; pharmacology ; Rats ; Rats, Sprague-Dawley