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Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
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Humans , Apolipoprotein E4/genetics , Cytosine , Mutation , Blastocyst , Heterozygote , Gene Editing , CRISPR-Cas SystemsABSTRACT
We report a fetus with ectopic connection of venous catheter into the dilated coronary sinus, right-sided aortic arch, left-sided ductal arch, and aberrant left subclavian artery detected by routine prenatal ultrasound screening at 23 +2 gestational weeks. The baby was born vaginally at 38 +2 gestational weeks with an Apgar score of 10 at both 1 and 5 min. The reexamination of neonatal echocardiography on the second day after birth showed dilation of the internal diameter of the coronary sinus, right-sided aortic arch, and aberrant left subclavian artery. Follow-up at 90 days after birth found no abnormal growth and development.
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Objective@#The purpose of this review of COVID-19 related research is to deepen our understanding of SARS-CoV-2, which would be inspire new ideas for targeted drug development and vaccine design, and further empower the prevention and control COVID-19.@*Methods@#Through literature research and data analysis, we explored the process and mechanism of epitranscriptomics modification to regulate the replication and infectivity of COVID-19.@*Results@#Provide important ideas and technical support for the prevention and control of SARS-CoV-2 infections and emerging epidemic diseases.@*Conclusions@#Taking the new research direction of epitranscriptomics as the starting point, it is expected to open up new scientific research concepts and paradigms.
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Objective:The purpose of this review of COVID-19 related research is to deepen our understanding of SARS-CoV-2, which would be inspire new ideas for targeted drug development and vaccine design, and further empower the prevention and control COVID-19.Methods:Through literature research and data analysis, we explored the process and mechanism of epitranscriptomics modification to regulate the replication and infectivity of COVID-19.Results:Provide important ideas and technical support for the prevention and control of SARS-CoV-2 infections and emerging epidemic diseases.Conclusions:Taking the new research direction of epitranscriptomics as the starting point, it is expected to open up new scientific research concepts and paradigms.
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We reported a case of fetus with right atrial isomerism diagnosed by ultrasound prenatally. Right atrial isomerism was suspected based on several kinds of abnormalities detected at 24 gestational weeks by ultrasound imaging, such as levocardia complicated by complex cardiovascular malformations (double outlet of right ventricle, atrioventricular septal defect, pulmonary artery dysplasia, bilateral superior vena cava and infracardiac total anomalous pulmonary venous drainage), abnormal right-sided stomach bubble, midline liver, suspicious absence of the spleen, juxtaposition of the abdominal aorta and the inferior vena cava to the left side, and mirror-image right bronchia. Autopsy confirmed all of the prenatal diagnosis with an additional finding of splenic dysplasia. Right atrial isomerism should be considered when ultrasound findings indicate complex cardiovascular malformations. Given the high mortality rate of right atrium isomerism, prenatal diagnosis is of great importance.
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Objective:To analyze the application of PDCA mode in the management of blood transfusion waiting time.Methods:Using random block design, 98 patients received blood transfusion during January to December 2018 were included into the before improvement; 32 patients received blood transfusion during January to June 2019 were included into the after improvement. Standard process of blood taking and transfusion was applied to the before improvement, while based on standard process, found out the deficiencies in the previous clinical practice, continuously improved the details of the process for the after improvement. Then blood transfusion waiting times were compared between the two groups.Results:The blood transfusion waiting time was (26.95±9.20) min before improvement and (25.59±4.16) min after improvement, with a significantly lower disqualification rate 6.25% (2/32) comparing with 26.53% (26/98) before improvement. The differences were statistically significant ( t value was 3.75, P<0.01; χ2 value was 5.87, P<0.05). Conclusions:The application of PDCA circulation management mode can shorten the blood transfusion waiting time and transfusion can be made within 30 minutes after blood taking so that nursing quality of transfusion in the ward can be improved.
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Objective@#To explore the relationship between family cohesion, psychological resilience and non-suicidal self-injury among middle school students.@*Methods@#By using the stratified random cluster sampling method, 2 065 students from 4 middle school from Fujian province were investigated with family cohesion scale, adolescent psychological resilience scale and adolescent self-injury behavior questionnaire.@*Results@#The report rate of self-injury was 40.34%, which differed by childhood migration experiences, parenting style as well as academic pressure (χ2=11.66，29.45，12.48，P<0.01). Total scores and dimensional scales in family cohesion and psychological resilience showed significant differences in students with or without self-injury (t=-8.33，-12.08，-7.29，-11.53，-3.38，-7.37，-7.68，P<0.01). The family cohesion was positively correlated with the psychological resilience and each dimension (r=0.27-0.56, P<0.01), but negatively correlated with non-suicidal self-injury (r=-0.18, P<0.01). The psychological resilience and each dimension were negatively correlated with non-suicidal self-injury (r=-0.24--0.14, P<0.01). Psychological resilience had a partial mediating effect between family cohesion and non-suicidal self-injury, with mediating effect accounting for 61.11% of the total effect.@*Conclusion@#Psychological resilience played a mediating role between family cohesion and non-suicidal self-injury. By promoting family cohesion to improve psychological resilience, it is helpful to prevent non-suicidal self-injury among middle school students.
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Objective To investigate and analyze the inpatient use of narcotic drugs, provide reference for clinical norms and rational use of narcotic drugs. Methods The narcotic prescription number, usage and cost were analyzed statistically. The inpatient narcotic use was analyzed by screening the dose form, indication, and dosage. Results The injections topped the list of narcotic prescriptions from year 2016 to 2019 with 15 820 (61.4%), 15 813 (61.5%), 16 682 (64.7%) and 17 293 (71.5%) prescriptions respectively. The oral and topical narcotic drugs were less prescribed. Although pethidine hydrochloride injection prescriptions decreased year by year, it still topped in the narcotic use with 8 009 (31.1%), 7 707 (30.0%), 7 151 (27.7%) and 6 844 (28.3%) prescriptions each year. Pethidine hydrochloride injection was mostly used for patients with cancer and chronic pancreatitis. Conclusion Doctors preferred to use injectable narcotics for patients with moderate to severe pain. Improper use of narcotic drugs was noticed, such as unsuitable choice of dose form, inappropriate use of pethidine hydrochloride injection, etc. Pharmacists should keep vigilant in prescription review and medication intervention for narcotic drugs to improve the standardization and rational use of narcotics.
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Objective@#To investigate the effects of sIL-13Rα2 on the apoptosis of goblet cell in nasal mucosa of allergic rhinitis rats.@*Methods@#Forty healthy male Wistar rats were randomly divided into 4 groups (10 rats per group): control group (group A), AR group (group B), sIL-13Rα2 group (group C) and triamcinolone acetonide group (group D). Ovalbumin (OVA) and aluminum hydroxide were used to establish the AR rat model. After the establishment of AR rat models, 50 μl PBS, 100 μg/50 μl IL-13Rα2 and 3.5 μg/50 μl triamcinolone acetonide were respectively dropped into each nasal cavity of every rat two times a week from 4 to 10 week in group B, group C and group D. Group A was operated with saline instead of OVA. The nasal mucosa tissues were collected at 24 h after the final administration. AB-PAS staining method was used to detect the quantity and secretion of goblet cells in the nasal mucosa tissue of all groups. Immunohistochemistry method was used to detect the expression of Bax proteins.Apoptosis was detected by TUNEL method.ANOVA analysis was used to compare multiple groups, and LSD-t test was used to compare the two groups.Pearson correlation analysis was used to analyze the correlation between the Bax positive cell rate of goblet cells and the rate of apoptotic cells. The difference was statistically significant with P<0.05.@*Results@#Compared with group A, there were more goblet cells and hypersecretion of mucus in the nasal mucosa tissue of rats in group B while fewer in group C. The goblet cells in group C and group D were significantly fewer than that in group B (0.639 00±0.831 vs 0.956 7±0.980, 0.661 90±0.657 vs 0.956 7±0.980, t value was 2.748, 2.767, respectively, all P<0.05). The immunohistochemistry results showed that the positive expression rates of Bax protein in goblet cells of group C and group D were significantly higher than that in group B (0.880 2±0.125 vs 0.568 7±0.953, 0.938 4±0.200 vs 0.568 7±0.953, t value was -2.292, -2.685, respectively, all P<0.05). The apoptosis rates of goblet cell in nasal mucosa of group C and group D were also significantly higher than that in group B (0.516 0±0.079 vs 0.274 0±0.056, 0.535 4±0.829 vs 0.274 0±0.056, t value was -17.671, -2.225, respectively, all P<0.05). The expression of Bax protein and apoptosis of goblet cells were positively correlated (r=0.859, P<0.01).@*Conclusion@#sIL-13Rα2 can induce apoptosis of the goblet cells in nasal mucosa of allergic rhinitis rats, by inhibiting IL-13 and up regulating Bax.
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Objective To develop a simple and fast UPLC-MS/MS method for determination of aconitine in biological human sample. Methods The biological human sample was treated by acetonitrile precipitation, and then analyzed on a UPLC C18(2.1mm×50mm, 1.7μm)column. The mobile phase consisted of acetonitrile-0.1% formic acid with gradient elution, at a flow rate of 0.4 mL/min, at 40℃. UPLC-MS/MS was performed in ESI source with MRM mode for quantification. Results The linear range of the concentration were 0.5~500ng/mL in blood and 1~1000ng/mL for aconitine in blood for aconitine (r>0.995). The relative recoveries of aconitine were in the range of 91.3%~110.2%, and the extraction recoveries were in the range of 72.8%~83.5%. The RSDs of intra-days and inter-day were both less than 14%. Conclusion The method is a simple, fast and could be used for determination of aconitine in biological human sample.
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Objective To explore the clinical effects of the packet therapy combined with Chinese prescrip-tion soaking in the treatment of patients with verruca plantaris,so as to provide clinical guidance and basis.Methods 101 patients with verruca plantaris were chosen as study objects,and they were divided into two groups,namely obser-vation group and control group.Observation group was treated by the packet therapy combined with Chinese prescrip-tion soaking,and control group was treated by Chinese prescription soaking.When they were cured for 4 weeks,the main symptoms and effective rate in the two groups were calculated and compared.For the recovery patients,when their drugs were withdrew for 8 weeks,the recurrence rate between the observation group and control group was compared.Results After being treated for 4 weeks,both of the skin lesion and pain degree between the observation group and control group had significant differences (Z=4.48,P0.05).Conclusion The packet therapy combined with Chinese prescription soaking is more effective than Chinese prescription soaking.
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Objective To study the interaction mechanism of anti-cancer drug docetaxel (DTX) andβ-tubulin, to determine the binding sites and the involved amino acids between the β-tubulin and docetaxel, and to analyze the dynamic combination process. Methods The docking binding energy and interaction sites of DTX molecules withβ-tubulin on the potential energy surface were calculated by molecular docking method. The dynamic interaction process of the low binding energy DTX with β-tubulin was simulated by molecular dynamics method. Results The results of molecular docking showed that there are three interaction sites, including N1, N2 and N3, between DTX and β-tubulin. The DTX molecules with structure of No.1, 2 and 4, which have excellent docking energy, were chose for molecular dynamics simulation. As a result, the dynamic change processes of the system complexes from non-equilibrium to equilibrium were obtained. The simulation results showed that the hydrogen bonds formed by the DTX with structure No.1 were significantly higher than those with structures No. 2 and 4. The solvent accessibility surface area of the DTX with structures No.1, 2 and 4 was higher than that of paclitaxel. Conclusion The model of DTX binding toβ-tubulin was established, which could provide theoretical guidance for the design and development of novel paclitaxel anticancer drugs.
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Objective To explore more accurate method about the time of pregnancy and gestational age of SD rats.Methods 7 to 8-week-old SD rats (18 females,6 males) were selected,the ratios of male to female were 2:1,5:2,1:1 and 4:1.Through vaginal plug observation,vaginal smear method,weight comparison method to verify the exact date of pregnancy in the next morning.Results Vaginal observed at milky vaginal plug sperm could be observed as sickle rat sperm head.Body weight of pregnant rats changed obviously.Three detection methods were used to detect the pregnancy time for 18 females.The positive rate of vaginal plug observation was 5.6％.The positive rate of vaginal smear method was 44.4％.The false negative rate of vaginal smear method was 11.1％.The positive rate of body weight method was 11.1％.The false positive rate was 5.6％.Conclusion The accuracy of vaginal smear is higher than the vaginal plug method and weight comparison method,the vaginal plug method can be used as the premise of the other two methods.Comparison method can be used as supplementary that the other two methods missed.
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Objective To observe the effect of Bupiyichang pills combined with levocetirizine in the treatment of 56 patients with chronic urticaria,so as to provide clinical guidance and basis.Methods 118 patients with chronic urticaria were selected for our study,and after informed consent they were randomly divided into observation group and control group.The observation group were was treated by Bupiyichang pills combined with levocetirizine,and the control group were was treated by levocetirizine.When they were curingAfter treatment for 10,20,and 30 days,the effective rates in the two groups were calculated and compared with each other.And at the day before treating and the day after treating for 20 days,the serum IgE levels in each group was detected and compared.The falling ranges between the two groups were calculated and compared.Results When they were curing treated for 10,20,and 30 days,the effective rates in the observation group were 76.79％,94.64 ％,85.71％,respectively,which in those of the control group were 59.68％,74.19％,64.52％,respectively,the differences between the two groups were statistically significance significant (x2 =3.94,9.11,6.97,all P ＜ 0.05).At the day before treating and the day after treating for 20 days,the serum IgE levels in the observation group were (384.71 ± 65.62) U/mL and (214.59 ±40.71) U/mL respectively,the difference was statistically significance significant (t =10.93,P ＜ 0.05);and the serum IgE levels in the control group were (380.25 ± 67.81)U/mL and (256.99 ± 53.21)U/mL respectively,the difference was statistically significancesignificant (t =9.37,P ＜ 0.05).The falling ranges in the observation group and the control group were (170.12 ± 35.59) U/mL and (123.26 ± 53.31) U/mL respectively,the difference was statistically significance significant between the two groups (t =7.82,P ＜ 0.05).Conclusion Bupiyichang pills combined with levocetirizine is more effective than single medication of levocetirizine.
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Objective To evaluate the curative effect of percutaneous puncturing drainage in treating liver abscess,to analyze the factors affecting curative effect,and to discuss the methods ior reducing mortality and complication rate as well as for shortening hospitalization time.Methods Clinical data of 121 patients with liver abscess,who were admitted to authors' hospital during the period from January 2011 to January 2016,were retrospectively analyzed.For the patients with confirmed liver abscess,adequate antiinfective therapy was adopted,at the same time CT scan was performed to evaluate the liquefaction of lesion,and under CT guidance percutaneous puncturing drainage was carried out.The mortality,complication rate,hospitalization time and the factors affecting curative effect were analyzed.Results A total of 121 patients with liver abscess were enrolled in this study.Two patients died after percutaneous puncturing drainage,the mortality was 1.6％.The factors affecting mortality included old age,underlying disease,the diameter and solid components of abscess.Two patients developed peripheral hepatic abscess and abdominal wall abscess,the complication rate was 1.6％,and clinical cure was achieved after active treatment in these two patients.The main factor affecting complication rate was inappropriate surgical manipulation.Clinical cure was achieved in all 119 patients,with a cure rate of 98.3％,and the average hospitalization time was (15.1±6.0)days.The risk factors that affected hospitalization time included the number of abscess X6 (r=0.232,P=0.021),abscess size X7 (r=0.26,P=0.005) and white blood cell count X8 (r=0.238,P=0.009).Multiple linear regression equation analysis indicated that statistically significant correlation existed between the above influence factors and hospitalization time (P＜0.05).The multiple regression equation was as follows:Y=-3.438+3.055X6+0.527X7+0.297X8,F=5.819,R2=0.416.No statistically significant correlation existed between the hospitalization time and other factors,including gender,age,diabetes mellitus,pathogenic bacteria and location of abscess (P＞0.05).Conclusion Percutaneous puncturing drainage is an effective treatment for liver abscess,it carries lower mortality and lower complication rate,and its hospitalization time is short.(J Intervent Radiol,2017,
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Objective To develop a sensitive and simple LC/MS method for determination of methomyl in blood samples.Methods Methomyl was extracted from blood by liquid-liquid extraction with ethyl acetate, and then analyzed on a Zorbax SB-C18 (2.1mm×50mm, 5μm) column. The mobile phase consisted of acetonitrile-0.1% formic acid with gradient elution, at a lfow rate of 0.5 mL/min, at 40℃. LC-MS was performed in ESI source with MRM mode for quantiifcation.ResultsThe linear range of the concentration were 0.05~2.0μg/mL for methomyl (r>0.995). The relative recoveries of methomyl were in the range of 90%~108%. The RSDs of intra-days and inter-day were both less than 15%.Conclusion The method is a simple, quick, sensitive and could be used for determination of methomyl in blood samples.
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Objective To evaluate the implementation of hospital pharmacy distribution for inpatient pharmacy services , with impact on understanding investigation for ward nurse awareness of the drug storage management ,and to optimize ward base drug administration .Methods By improving the drug delivery service process in a hospital ward ,the statistical base vari-ety and number of the base drugs were counted two years in 2012 and in 2014 respectively ;with a questionnaire analysis in ward nurses on base drug awareness and drug management situation .Results After the drug distribution process optimization , time that nurses receive medicines from pharmacies decreased from 90 min to 20 min;base ward drugs from 2012 of 16 catego-ries ,237 varieties ,down to 2014 of 13 categories ,209 species .Questionnaire survey results showed that the ward nurse awareness of drug administration should be improved further .Conclusion By optimizing the drug distribution process ,reduced storage ward medicines can increase the time nurses for patients and services as well as reduce the risk faced by the ward base drug administration .
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Objective To establish the chromatographic fingerprint of mushroom polysaccharides by 1-phenyl-3-methyl-5-pyrazolone( PMP) pre-column derivatization. Methods The mushroom polysaccharides was extracted by hot distilled water, precipitated by alcohol, and hydrolyzed into monosaccharides by Trifluoroacetic Acid (TFA). The hydrolysate was derivatized with 1-phenyl-3-methyl-5-pyrazolone ( PMP ) and tested via HPLC to study the monosaccharide components in mushroom polysaccharides. Results Fingerprint was established with 13 common peaks, 6 peaks in which were identified as mannose, D-glucuronic acid, D-glucose, galactose, xylose and L-fucose. The glucose accounted for the most, followed by mannose, galactose and fucose. Conclusion Development of fingerprint chromatogram by HPLC is a stable, simple, and repeatable way, which can be applied to the quality control of mushroom polysaccharides.
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<p><b>BACKGROUND</b>We evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio (the ratio between metastatic lymph nodes and total dissected lymph nodes, MLNR) in patients with gastric adenocarcinoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric cancer.</p><p><b>METHODS</b>From January 2005 to December 2010, 1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were included. In particular, lymph node metastasis was not present in 515 patients. The number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease outcome. The survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier plots.</p><p><b>RESULTS</b>The overall 5-year survival rate was 54% in this group. Univariate analysis revealed that age category, macroscopic appearance, histological grade, tumor size, depth of primary tumor invasion, number of metastatic lymph nodes, metastatic lymph nodes ratio, tumor, nodes, metastasis-classification (TNM) stage and status of lymphovascular, and vessel invasion have significant impact on survival. The number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival (P < 0.001). However, in multivariate analyses, only the metastatic lymph nodes ratio was identified to be an independent prognostic factor (P < 0.001). The number of removed lymph nodes in node-negative was a strong prognostic factor of survival, the more lymph nodes dissected, the better the survival.</p><p><b>CONCLUSIONS</b>The metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph nodes. The number of removed lymph nodes might be an important prognostic factor for gastric cancer without lymph node metastasis.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Adenocarcinoma , Mortality , General Surgery , Gastrectomy , Lymph Node Excision , Lymphatic Metastasis , Neoplasm Staging , Prognosis , Stomach Neoplasms , Mortality , General SurgeryABSTRACT
Objective:To evaluate in vitro antifungal activities of zhexinmycin against dermatophytes. Methods: The minimum in-hibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of zhexinmycin against 7 strains of dermatophytes were determined by using broth microdilution method according to CLSI M-38A. Results:The MIC of zhexinmycin against dermatophytes was within the range of 0. 125-2. 000μg·ml-1 . The MFC was within the range of 0. 250-4. 000μg·ml-1 . Conclusion:Zhexinmycin shows strong in vitro antifungal effect on multiple fungi such as Epidermophyton floccosum, Trichophyton rubrum, Trichophyton violaceum, Mi-crosporum canis, Trichophyton mentagrophytes, Trichophyton tonsurans and Microsporum gypseum.