Clustered regulatory interspaced short palindromic repeats (CRISPR) found in bacteria and archaea genome that contains multiple short repeats loci, provides acquired immunity against invading foreign DNA via RNA-guided DNA cleavage. The first inkling of this hot new genetic engineering tool turned up in 1987, when a research team observed an oddly repetitive sequence at one end of a bacterial gene. Now three types of CRISPR/Cas system have been identified: types I, II and III. In the type II CRISPR/Cas9 system, short segments of foreign DNA termed 'spacers' are integrated within the CRISPR genomic loci, transcribed and processed into short CRISPR RNA (crRNA). These crRNAs anneal to trans-activating crRNA (tracrRNA) and direct sequence-specific cleavage in that a double-strand break (DSB) is generated by Cas proteins. Based on these findings, various genetic methods, including gene targeting (Gene disruption), gene insertion, gene correction etc., are being designed to manipulate the genomes of different species at specific loci. Compared with zinc finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), CRISPR/Cas9 is simpler with higher specificity and less toxicity. This review summarizes recent progress, discusses the prospects of CRISPR/Cas9 system, with an emphasis on its structure, principle, applications and potential challenges, and provides a useful reference for researchers who are interested in this new technique.
Bacteria ; CRISPR-Cas Systems ; DNA ; Genetic Engineering ; Genomics ; RNA

Objective:To investigate the serum endothelial cell specific molecule-1 (ESM-1) level and its clinical significance in patients with hypertensive disorders complicating pregnancy (HDCP).Methods:Three hundred pregnant women with HDCP (HDCP group) and 300 pregnant women undergoing health check-ups (healthy control group) from January to December 2019 in Maternity and Child Health Hospital of Wenling City of Zhejiang Province were selected. In HDCP group, hypertension during pregnancy was in 94 cases, mild preeclampsia was in 131 cases, and severe preeclampsia was in 75 cases. The serum ESM-1, serum uric acid and 24-hour urine protein levels were detected. The incidences of neonatal asphyxia, fetal distress, cesarean section, polyhydramnios, premature rupture of membranes and postpartum hemorrhage in the HDCP group were recorded.Results:The serum ESM-1, serum uric acid and 24-hour urine protein in HDCP group were significantly higher than those in healthy control group: (0.42 ± 0.05) μg/L vs. (0.33 ± 0.04) μg/L, (262.34 ± 23.18) mmol/L vs. (212.37 ± 22.16) mmol/L and (0.36 ± 0.07) g vs. (0.11 ± 0.03) g, and the differences were statistical significant ( P<0.01). The correlation analysis results showed that the serum ESM-1 was positive correlation with serum uric acid and 24-hour urine protein in HDCP pregnant women ( r = 0.497 and 0.512, P<0.01). The serum ESM-1 in pregnant women with mild preeclampsia and severe preeclampsia were significantly higher than that in pregnant women with hypertension during pregnancy: (0.44 ± 0.05) and (0.51 ± 0.06) μg/L vs. (0.38 ± 0.04) μg/L, the serum ESM-1 in pregnant women with severe preeclampsia was significantly higher than that in pregnant women with mild preeclampsia, and the differences were statistical significant ( P<0.05). With the median serum ESM-1 (0.41 μg/L) as the boundary, pregnant women with HDCP were divided into high ESM-1 group (154 cases) and low ESM-1 group (146 cases). The incidences of neonatal asphyxia, fetal distress, cesarean section, polyhydramnios, premature rupture of membranes and postpartum hemorrhage in high ESM-1 group were significantly higher than those in low ESM-1 group: 14.94% (23/154) vs. 6.16% (9/146), 26.62% (41/154) vs. 9.59% (14/146), 46.10% (71/154) vs. 29.45% (43/146), 25.32% (39/154) vs. 3.42% (5/146), 23.38% (36/154) vs. 4.11% (6/146) and 20.13% (31/154) vs. 7.53% (11/146), and the differences were statistical significant ( P<0.01). Conclusions:Serum ESM-1 level is elevated in pregnant women with HDCP . Serum ESM-1 level is closely related to the severity of HDCP and pregnancy outcomes.

In the complications of dental implant treatment, the mechanical complications, such as central screw breakage, are often complex and serious. This article analyzes factors that affect the loosening of the central screw. Understanding relevant risk factors can prompt doctors to take corresponding strategies to reduce the possibility of complications in clinical operations. After encountering broken cases, this paper also gives some ideas and methods of treatment, and finally summarizes clinical suggestions for preventing the central screw fracture.

Objective To study the chronic neurotoxicity of aluminum through observing the adverse effect of long term intake of aluminum on the memory of rats.Methods 40 Wistar rats were randomly divided into 4 groups and given Al2(SO4)3 through drinking water for 6 months,the concentration of Al3+ in the waters were 0.12 mg/L,40 mg/L,400 mg/L and 2 000 mg/L respectively,then passive avoidance tests were carried out.One month before pregnancy,the dams were given Al3+ of 40 mg/L and 2 000 mg/L respectively,after the offspring were born,the group given high[Al3+] was subdivided into two groups,one continuously drank the water with high [Al3+],the other drank the water without Al3+.The dams drinking water with low [Al3+] and their offspring continued to drink the same water as before.At the age of three months,all the offspring were examined with passive avoidance tests.Results The memory acquirement in all adult rats were not abnormal,but memory retention were severely damaged (P0.05).The rats continuously drinking water with high [Al3+] after birth had significant damage both in memory acquirement and in retention (P

Objective To analyze the distribution of multiple myeloma (MM) literature in Chinese periodicals and to find out the core periodicals about MM.Methods Periodical literature that involved with MM in the article titles from January 2008 to December 2014 on the Wanfang medical database was collected and searched.Bibliometric method was used to analyze journal date and journal distribution.Results 456categories of periodicals had published literature about MM.The number of articles about MM published in the top 10 journals was more than 30,accounting for 27.00 ％ of all published MM literature,which were highly effective core journals.The number of articles about MM published in the top 3 journals was more than 100,accounting for 15.59 ％ of all published MM literature.The number in Journal of Leukemia & Lymphoma had reached 187,accounting for 6.43 ％ of the total.Conclusions The core journals about MM provide the key approach to help MM medical personnel to select useful information efficiently.Furthermore,the core journals are not only the significant gist for authors who plan to contribute their articles to relevant MM periodicals,but also the necessary reference tools for medicine workers who engage in basic and clinical research and teaching.

Objective:To investigate the clinical features and their relationship with mortality of coronavirus disease 2019 (COVID-19) in people living with human immunodeficiency virus (HIV).Methods:A thorough literature review was conducted about peer-reviewed publications including cohort study, cross-sectional research, and case series on HIV/2019 novel coronavirus (2019-nCoV) coinfection from January to August 2020. Systemic review and meta-analysis were used to investigate the correlation between mortality and clinical features including age, comorbidities, CD4 + T lymphocyte count, HIV RNA level, and anti-retroviral therapy. Stata 15.0 software was used for meta-analysis. Results:Twenty-four articles were included with a total of 939 HIV/2019-nCoV coinfected patients. Overall mortality was 10.3% (97/939). Advanced age and comorbidities, including hypertension, diabetes mellitus, renal insufficiency, chronic obstructive pulmonary disease/asthma and tumor were all significantly associated with mortality (95% confidence interval 0.005-0.050, 0.042-2.294, 0.390-2.754, 0.513-2.848, 0.348-3.743 and 1.943-7.101, respectively, P=0.021, 0.043, 0.012, 0.008, 0.022 and 0.005, respectively). There were no correlations between mortality and CD4 + T lymphocyte count <200/μL or >500/μL, HIV RNA was below the lower limit of detection, or anti-retroviral drug (including tenofovir) (all P>0.05). Conclusions:The overall prognosis of COVID-19 in people living with HIV is similar to general population. Increased mortality correlates with advanced age and comorbidities including hypertension, diabetes mellitus, renal insufficiency, chronic obstructive pulmonary disease/asthma and tumor. Low CD4 + T lymphocyte count does not affect mortality. Preliminary results indicate that anti-retroviral drugs have no protective effect on COVID-19.

The experiment method of "Liquid-vapor" permeation for nitro oxidizer's skin protective materials by the indicator of pH test paper is developed,and the method for cankerous testing and evalution roles are confirmed too.The result of the experiment shows that butyl rubber and halogenated butyl rubber have better protective performances for "liquid-vapor" permeation of nitro oxidizer,while fluorine rubber,polyethylene and polyterafluoroethylene have better cankerous protection capabilities.

Objective To explore the method of permeability for skin protective materials of rocket propellant based on the design and make of sealing container. Methods The propellant mass permeated per minute and per square centimeter was calculated by testing the mass through the sample at the fixed time in the sealing container. Results The method of permeability for skin protective materials against rocket propellant was developed by the mass variation of propellant in the sealing container. The limits of 100?g /(cm2?min) was raised to assess if the material had the protection ability. In the meantime, the reliability of material protection behavior was improved. Conclusion The science of the method developed is confirmed by comparing the permeation performance of protection materials at home and abroad, and the method can be the basis to assess the ability of protection materials.

Understanding and learning the up-date clinical information of evidence-based medicine are the important part of knowledge for clinical postgraduates and are the basic ability required in their future clinical work.The necessity and role of literature retrieval course were studied with meta analysis of literature retrieval course teaching as the core content,and with meta analysis of literature retrieval course teaching as the writing objective.The literature retrieval course teaching process was displayed by demonstrating the case design and analysis,retrieval methods and their implementation in different stages of literature retrieval course teaching.

Objective To study the correlation between normal level of thyroid hormone and gensini coronary scor-ing system. Methods Coronary heart disease patient who were treated with Cardio-angiography (CAG) (n=231) were divid-ed into 4 groups based on gensini coronary score. All the patients were examined with indexes include total triiodothyronine (TT3), total thyronine(TT4), free thyronine(FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH). And correla-tion between thyroid hormone level and gensini coronary scoring system was studied by Spearman correlation analysis and Multiple regression analysis. Results No significant difference was found in the levels of TT3, TT4, FT4, Cholesterol(CHO) and Triglyceride(TG) between the all 4 groups (P>0.05). FT3 and HDL-C decreased with the increase of extent of coronary artery lesions(P<0.01), and AGE and LDL-C raised with the coronary artery lesions extent (P<0.05). Gensini coronary scoring system was linearly negatively correlated with FT3, HDL-C and positively correlated with age and LDL-C. Age, FT3,HDL-C,LDL-C was independently correlated to Gensini score. Conclusion The lower level of FT3 is an indepen-dent risk factor for CHD.