CRISPR/Cas-mediated DNA base editing technology and its application in biomedicine and agriculture / 生物工程学报

In recent years, the genome editing technologies based on the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) have developed rapidly. The system can use homologous directed recombination (HDR) to achieve precise editing that it medicated, but the efficiency is extremely low, which limits its application in agriculture and biomedical fields. As an emerging genome editing technology, the CRISPR/Cas-mediated DNA base editing technologies can achieve targeted mutations of bases without generating double-strand breaks, and has higher editing efficiency and specificity compared with CRISPR/Cas-mediated HDR editing. At present, cytidine base editors (CBEs) that can mutate C to T, adenine base editors (ABEs) that can mutate A to G, and prime editors (PEs) that enable arbitrary base conversion and precise insertion and deletion of small fragments, have been developed. In addition, glycosylase base editors (GBEs) capable of transitioning from C to G and double base editors capable of editing both A and C simultaneously, have been developed. This review summarizes the development, advances, advantages and limitations of several DNA base editors. The successful applications of DNA base editing technology in biomedicine and agriculture, together with the prospects for further optimization and selection of DNA base editors, are discussed.

Knockdown the expression of ku70 and lig4 in HEK293T cells by CRISPR/Cas13 system / 生物工程学报

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system is a hotspot of gene editing and gene expression research, in which CRISPR/Cas13 system provides a new direction for RNA interference and editing. In this study, we designed and synthesized the corresponding gRNAs of CRISPR/Cas13a and CRISPR/Cas13b systems in non-homologous end joining (NHEJ) pathway, such as Ku70 and Lig4, and then detected the expression of ku70 and lig4 in HEK293T cells. The CRISPR/Cas13a system could efficiently knockdown the mRNA expression of ku70 and lig4 more than 50%, and CRISPR/Cas13b system also suppressed ku70 and lig4 about 92% and 76%, respectively. Also, CRISPR/Cas13a, b systems could down-regulate Ku70 and Lig4 proteins level to 68% and 53%, respectively. The study demonstrates that the CRISPR/Cas13 system could effectively knockdown the expression of RNA and protein in HEK293T cells, providing a new strategy for gene function and regulation research.

The relationship between air quality improvement and the onset of type 2 diabetes mellitus: a prospective cohort study / 公共卫生与预防医学

Objective To explore the effect of decreased air pollutants concentrations on the incidence of Type 2 Diabetes Mellitus (T2DM). Methods A prospective cohort was designed in Tianjin where the air quality gradually improved from 2014 to 2018. A total of 5 077 community residents (18-90 years old) were recruited as the baseline population from 2013 to 2014. From 2014 to 2018 follow-up was carried out year by year to observe the new incidence of T2DM in the cohort. The HR and 95%CI (95% confidence interval) were calculated with the multiple Cox proportional hazard regression model to evaluate the effect of the decrease in the concentrations of SO2, NO2, and particulate matters with diameters 10, PM2.5) on the incidence of T2DM. Results The cohort was followed up year by year from 2014 to 2018, with a cumulative follow-up of 25 385 person-years over the 5 years. At the same time, the air quality of Tianjin was significantly improved. Statistical analysis results after covariate adjustment revealed that the risk of T2DM in the population decreased by 0.172, 0.124, and 0.210 times, for a decrease of 10 μg/m3 in the annual average concentrations of SO2, PM10, and PM2.5 each, respectively (SO2：HR=0.828，95%CI=0.757-0.907；PM10：HR=0.876，95%CI=0.816-0.941；PM2.5：HR=0.790，95%CI=0.694-0.899). Conclusion The implementation of environmental protection measures to improve air pollution could reduce the risk of T2DM in the population and control the increasing prevalence.

Effects of multimodal analgesia on inflammatory cytokines and rapid rehabilitation after surgery in 3 -6 months infant with Hirschprung＇s disease / 中华实用儿科临床杂志

Objective To study the effects of patient-controlled intravenous analgesia( PCIA)with Dexme-detomidine,Ropivacaine by local incision infiltration and combined analgesia on inflammatory factors and rapid rehabili-tation in infants aged 3-6 months after radical resection of megacolon. Methods From June 2016 to March 2018,90 infants aged 3-6 months underwent radical resection of megacolon in Henan Provincial Children＇s Hospital as the sub-jects. According to the postoperative analgesia mode applied to the children,they were divided into Dexmedetomidine group,Ropivacaine group and combined group( Dexmedetomidine PCIA combined with local infiltration of Ropiva-caine),30 cases in each group. The serum levels of interleukin( IL)-6 and IL-10 were measured and recorded 2 hours before operation and 24 hours after operation,and the analgesic scores of 4,8,12 and 24 hours after operation were recorded. The rapid recovery index of each group,standard and the number of complications were compared. Results Compared with 2 hours before operation,the serum levels of IL-6 in the Dexmedetomidine group,Ropiva-caine group and combined group[(24. 61 ± 1. 44)ng/L υs.(13. 84 ± 0. 65)ng/L,(26. 39 ± 1. 29)ng/L υs.(13. 85 ± 0. 67)ng/L,(20. 58 ± 2. 06)ng/L υs.(13. 87 ± 0. 63)ng/L],IL-10[(27. 63 ± 1. 52)ng/L υs.(15. 79 ± 1. 48) ng/L,(28. 29 ± 2. 34)ng/L υs.(15. 41 ± 1. 37)ng/L,(23. 21 ± 2. 71)ng/L υs.(15. 47 ± 1. 52)ng/L]were signifi-cantly higher(all P<0. 05),while the levels of IL-6,IL-10 in combined group were lower than those in Dexmedeto-midine group and Ropivacaine group(ta =9. 172,9. 835;tb =10. 221,11. 034,all P<0. 05). At 4 h,8 h,12 h,24 h after operation. The analgesic scores in combined group were(1. 89 ± 0. 23)scores,(1. 87 ± 0. 15)scores,(1. 95 ± 0. 17)scores,(2. 08 ± 0. 18)scores,those of dexmedetomidine group were(2. 06 ± 0. 24)scores,(2. 08 ± 0. 18) scores,(2. 76 ± 0. 29)scores,(2. 55 ± 0. 31)scores,those of Ropivacaine group were(2. 10 ± 0. 26)scores,(2. 15 ± 0. 26)scores,(2. 32 ± 0. 19)scores,(3. 00 ± 0. 28)scores,and the analgesic scores in combined group were signifi-cantly lower than those in Dexmedetomidine group and Ropivacaine group( ta =8. 526,9. 364,10. 287,9. 521;tb =8. 729,9. 514,11. 037,9. 184,all P<0. 05). In comparison with the first exhaust time,anal extubation time,hospitali-zation days,hospitalization expenses and antibiotic use time in the three groups,it was found that combined group was significantly better than Dexmedetomidine group and Ropivacaine group(ta =8. 315,8. 294,7. 883,9. 261,10. 487;tb =8. 582,8. 329,7. 916,9. 348,10. 862,all P<0. 05). The incidence of complications in the combined group,Dexme-detomidine group,and Ropivacaine group were not significantly different in 3 groups( χ2 = 0. 577,P = 0. 749 ). Conclusions The continuous anesthesia of Dexmedetomidine combined with local infiltration of Ropivacaine incision can alleviate the postoperative inflammatory reaction and promote the rapid recovery of children.

Effects of multimodal analgesia on inflammatory cytokines and rapid rehabilitation after surgery in 3-6 months infant with Hirschprung′s disease / 中华实用儿科临床杂志

Objective@#To study the effects of patient-controlled intravenous analgesia(PCIA) with Dexmedetomidine, Ropivacaine by local incision infiltration and combined analgesia on inflammatory factors and rapid rehabilitation in infants aged 3-6 months after radical resection of megacolon.@*Methods@#From June 2016 to March 2018, 90 infants aged 3-6 months underwent radical resection of megacolon in Henan Provincial Children′s Hospital as the subjects.According to the postoperative analgesia mode applied to the children, they were divided into Dexmedetomidine group, Ropivacaine group and combined group (Dexmedetomidine PCIA combined with local infiltration of Ropivacaine), 30 cases in each group.The serum levels of interleukin(IL)-6 and IL-10 were measured and recorded 2 hours before operation and 24 hours after operation, and the analgesic scores of 4, 8, 12 and 24 hours after operation were recorded.The rapid recovery index of each group, standard and the number of complications were compared.@*Results@#Compared with 2 hours before operation, the serum levels of IL-6 in the Dexmedetomidine group, Ropivacaine group and combined group [(24.61±1.44) ng/L vs.(13.84±0.65) ng/L, (26.39±1.29) ng/L vs.(13.85±0.67) ng/L, (20.58±2.06) ng/L vs.(13.87±0.63) ng/L], IL-10[(27.63±1.52) ng/L vs.(15.79±1.48) ng/L, (28.29±2.34) ng/L vs.(15.41±1.37) ng/L, (23.21±2.71) ng/L vs.(15.47±1.52) ng/L] were significantly higher (all P<0.05), while the levels of IL-6, IL-10 in combined group were lower than those in Dexmedetomidine group and Ropivacaine group (ta=9.172, 9.835; tb=10.221, 11.034, all P<0.05). At 4 h, 8 h, 12 h, 24 h after operation.The analgesic scores in combined group were(1.89±0.23) scores, (1.87±0.15) scores, (1.95±0.17) scores, (2.08±0.18) scores, those of dexmedetomidine group were(2.06±0.24) scores, (2.08±0.18) scores, (2.76±0.29) scores, (2.55±0.31) scores, those of Ropivacaine group were(2.10±0.26) scores, (2.15±0.26) scores, (2.32±0.19) scores, (3.00±0.28) scores, and the analgesic scores in combined group were significantly lower than those in Dexmedetomidine group and Ropivacaine group(ta=8.526, 9.364, 10.287, 9.521; tb=8.729, 9.514, 11.037, 9.184, all P<0.05). In comparison with the first exhaust time, anal extubation time, hospitalization days, hospitalization expenses and antibiotic use time in the three groups, it was found that combined group was significantly better than Dexmedetomidine group and Ropivacaine group(ta=8.315, 8.294, 7.883, 9.261, 10.487; tb=8.582, 8.329, 7.916, 9.348, 10.862, all P<0.05). The incidence of complications in the combined group, Dexmedetomidine group, and Ropivacaine group were not significantly different in 3 groups(χ2=0.577, P=0.749).@*Conclusions@#The continuous anesthesia of Dexmedetomidine combined with local infiltration of Ropivacaine incision can alleviate the postoperative inflammatory reaction and promote the rapid recovery of children.

Application of enhanced recovery after surgery in perioperative treatment of type biliary dilatation in children / 中华肝胆外科杂志

Objective To study the clinical value of enhanced recovery after surgery (ERAS) in the perioperative treatment of type Ⅰ (Todami,1975) biliary dilatation (BD) of children.Methods To retrospectively analyze the data of children with type Ⅰ BD who were treated in the General Surgery Department of Zhengzhou Children's Hospital from June 2014 to May 2018.A total of twenty children with type Ⅰ BD treated with ERAS and 20 children treated with the traditional method in our department were selected in this study using the random number table method.Postoperative indicators (including operation time,first defecation time,changes in amylase in blood and abdominal cavity exudates,length of hospital stay,and hospitalization fee) and relevant postoperative complications (including sore throat,nausea and vomiting,urethral pain,upper respiratory tract infection,incision wound infection,adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula) of the ERAS group and the control group were compared.Results The first defecation time,length of hospital stay and hospitalization fee were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [first defecation time (1.98 ± 0.25) d vs.(2.25 ± 0.31) d;length of hospital stay (6.91 ± 1.25) d vs.(9.95 ± 1.53) d;hospitalization fee (23.32 ± 2.25)thousand yuan vs.(25.99 ±3.10) thousand yuan].Moreover,the incidences of sore throat,nausea and vomiting,urethral pain and upper respiratory tract infection were significantly lower in the ERAS group than the control group (all P ＜ 0.05) [the incidences of sore throat (5.0％ vs.45.0％);the incidences of sickness and vomiting (5.0％ vs.30.0％);the incidences of urethral pain (5.0％ vs.45.0％);the incidences of upper respiratory tract infection (5.0％ vs.40.0％)].On the other hand,there were no significant differences in the mean operation times,changes in amylase levels in the blood or abdominal cavity exudates,incision wound infection,and incidences of adhesive intestinal obstruction,anastomotic leakage and pancreatic fistula (all P ＞ 0.05).Conclusions ERAS for type Ⅰ BD surgery was safe and reliable in children.It effectively promoted recovery of postoperative gastrointestinal function and reduced the incidence of complications.

Value of peripheral NLR and PLR in prediction of the survival of patients with neuroblastoma / 中华普通外科杂志

Objective To investigate value of peripheral NLR and PLR for the survival of patients with neuroblastoma.Methods The clinical data of 41 neuroblastoma patients were analyzed by the Kaplan-Meier,Log-rank test,and multivariate COX regression.Results NLR,PLR levels of neuroblastoma patients were significantly higher than that in the healthy control group (1.81 ±0.29 vs.1.07 ±0.29,P ＜ 0.01) (169 ± 23 vs.76 ± 3,P ＜ 0.01);The elder the age,the higher the clinical stages,the higher the serum levels of NSE,and urine VMA were,the higher was the NLR (x2 =3.93,6.286,7.676,6.689,all P＜0.05) and PLR (x2 =4.111,5.707,8.019,8.922,all P ＜0.05).The higher the serum level of LDH,the higher was the NLR (x2 =7.769,P =0.02).3-year overall survival in low NLR group was 84％ and that in high NLR group was 73％ (x2 =4.002,P =0.045);3-year progression-free survival in low NLR group was 74％ and that in high NLR group was 50％ (x2 =4.082,P =0.043);3-year progression-free survival of low PLR group was 85％ and high PLR group was 38％ (x2 =9.388,P =0.002).The clinical stages,MYCN genetic expression,NLR levels were independent factors for the overall survial in patients with neuroblastoma (P ＜ 0.05).Conclusion Pretreatment NLR level can effectively predict the prognosis of neuroblastoma.

Analysis of correlation between immunosuppression and organ dysfunction in children with sepsis / 临床儿科杂志

Objective To analyse the relationship between immunosuppression and severity of sepsis in children,thus to explore the role of immunity in the progression of sepsis and provide a reference for the treatment of sepsis in children.Methods In this retrospective study,375 children with sepsis were included.Blood specimens were collected for the analysis of lymphocyte subsets and humoral immunity in 24 hours after admission into ICU.Univariate analysis was performed between immunity indices and organ dysfunction.Logistic stepwise regression was used to screen out the risk factors of multiple organ dysfunction (MKDS) and mortality.Results Sepsis children were divided into three groups,no organ dysfunction,single organ dysfunction and multiple organ dysfunction.NK cell percentage,CD4/CD8 and C3 were different among three groups,and significantly lower in MODS children.Multivariate analysis showed decreased CD4/CD8 (OR=0.66,95％CI:0.51-0.85).C3 level (OR=0.20,95％CI:0.10-0.42) were associated with MODS.CNS infection (OR=2.54,95％CI:1.35-4.77) and pneumonia infection (OR=2.29,95％CI:1.36-3.83) were also risk factors of MODS.Depletion of C3 (OR=0.26,95％CI:0.09-0.76) and pneumonia infection (OR=2.61,95％CI:1.12-6.09) were risk factors of mortality.Conclusions CD4/CD8 and complement C3 were significantly decreased in sepsis children with MODS,immunosuppression may play an important role in the development of MODS in children with sepsis.Baseline CD4/CD8 and C3 level could be potential prognostic markers of sepsis.

Distribution and clinical significance of EML4-ALK fusion gene in phase Ⅰ lung cancer / 中华胸心血管外科杂志

Objective To detect the mutation frequency of EML4-ALK fusion gene in lung cancer patients, and to inves-tigate the distribution of mutation character for EML4-ALK fusion gene in Ⅰ stage lung cancer patients and clinical features as well as provide a reference for the individual treatment of lung cancer .Methods 256 fresh tumor tissue specimens of lung cancer patients were screened from the specimen bank of our hospital and all the patients had accepted the surgical treatment from February 2013 to December 2014.Total RNA was extracted and then be transcribed into cDNA, the amplification-refrac-tory mutation system(ARMS) was used to detect mutation of EML4-ALK fusion gene.The results according to the positive con-trol, negative control and RNA quality control for EML4-ALK fusion type were analyzed.Results During the 256 patients ofⅠ stage lung cancer, there were 17 patients(6.64%) had mutations in EML4-ALK fusion gene.In lung adenocarcinoma mu-tation rate(16/207, 7.73%) was higher than that of lung squamous cell mutation rate(1/39, 2.56%), lung adeno-squamous mutation rate(0/4, 0) and large cell carcinoma(0/5, 0) of the mutation rate;young lung cancer patients( <63 years) of the mutation rate(14/139, 10.07%) was significantly higher than the high age of lung cancer patients(≥63 years old) mutation rate(3/117, 2.56%), P =0.009.EML4-ALK fusion with tumor invasion and visceral pleura group incidence (9/80, 11. 25%) was significantly higher than that of non-invasive and visceral pleura group incidence rate(8/176, 4.55%), P =0.045.Conclusion The occurence of EML4-ALK fusion correlates with patients’ age as well as whether visceral pleura is in-vaded, type 1 EML4-ALK fusion was detected more in phase I lung cancer patients.

Correlation of complement depletion and the severity of sepsis in children / 中华实用儿科临床杂志

Objective To analyze the relationship between complement key component C3,C4 and the severity of sepsis in children,in order to explore the role of complement activation in the progression of sepsis and provide a reference for diagnosis and treatment of severe sepsis.Methods Four hundred and twenty-four children diagnosed as sepsis from December 2012 to December 2015 in Children's Hospital of Nanjing Medical University were enrolled in this study,among whom 347 children with sepsis were eligible for the following research including 169 cases of common sepsis and 178 cases of severe sepsis.Blood specimens were collected in 24 hours after their admission into pediatric intensive care unit(PICU) for the analysis of lymphocyte subsets,humoral immunity,blood routine analysis,coagulation,liver and renal function analysis.General information was collected by consulting their medical records,laboratory analysis and clinical treatment.The relationship between complement C3,C4 and the severity of sepsis was analyzed,and the correlation between C3 and coagulation,liver,renal,myocardium damage was also studied.Logistic regression was used to analyze the relationship between C3 and the progression to severe sepsis and multiple organ dysfunction syndrome(MODS),while Cox regression was used for survival analysis.Results Natural killer(NK) cell percentage was lower in severe sepsis group than that in common sepsis group [6.6％ (3.7％,10.7％) vs.8.5％ (4.7％,13.3％),Z =2.635,P =0.008],while C3 decreased in severe sepsis group compared with common sepsis group [0.653 (0.462,0.985) g/L vs.0.991 (0.678,1.265) g/L,Z =5.684,P ＜ 0.001],and C4 decreased in severe sepsis group compared with common sepsis group [0.160(0.102,0.244) g/L vs.0.190(0.121,0.265) g/L,Z =2.513,P =0.012].The proportion of severe pneumonia was higher in severe sepsis group than that in common sepsis group (34.3％ vs.19.5％,x2 =9.540,P =0.002),and liver function damage proportion was increased in severe sepsis group than that in common sepsis group (48.3％ vs.16.0％,x2 =41.28,P ＜0.001),and the duration of PICU treatment was longer in severe sepsis group than that in common sepsis group[10.7(6.5,17.4) d vs.7.5(4.0,12.4) d,Z =-4.039,P ＜0.001].C3 was significantly decreased in children with single organ dysfunction,multiple organ dysfunction and death group compared with common sepsis group (K =33.04,P =0.001),and the median of each group decreased with the severity of sepsis,but C4 had no difference among 4 groups (K =7.36,P =0.061).C3 was positively correlated with coagulation marker platelet (p =0.31,P ＜ 0.001) and fibrinogen (ρ =0.53,P ＜ 0.001),but negatively correlated with international normalized ratio (INR) (ρ =-0.39,P ＜ 0.001) and activated partial thromboplastin time (p =-0.34,P ＜ 0.001).C3 was also negatively correlated with liver damage marker alanine transaminase (ρ =-0.30,P ＜ 0.001) and total bilirubin (ρ =-0.28,P ＜ 0.001),and had a negative correlation with renal function marker creatinine (p =-0.24,P ＜ 0.001) and myocardial damage marker creatine kinase-MB (p =-0.27,P ＜ 0.001).The depletion of C3 was a risk factor of severe sepsis(OR =3.45,P ＜ 0.001) and MODS(OR =3.03,P =0.005) after being adjusted for confounding factors by using Logistic regression.In stratification analysis,C3 depletion was still a risk factor of severe sepsis (OR =2.78,P =0.019) and MODS (OR =3.57,P =0.015) among children less than 1 year old,and was also a risk factor of severe sepsis(OR =4.76,P =0.008) among children more than 1 year old as well.In children without liver function damage,C3 depletion was still a risk factor of severe sepsis(OR =4.17,P =0.002) and MODS(OR =9.09,P =0.002).Cox regression showed that C3 depletion was a hazard in 28-day mortality (HR =3.57,P =0.026) in children with sepsis.Conclusion The decrease of C3 is correlated with coagulation dysfunction and organ damage marker,while C3 depletion was a risk factor of severe sepsis,MODS and 28-day mortality,and could be a potential prognostic marker of children with sepsis.

Comparison of sufentanil-tramadol PCIA between laparoscopic cholecystectomy and gynecological laparoscopy / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the differences of postoperative patient-controlled intravenous analgesia for laparoscopic cholecystectomy and gynecological laparoscopy in female patients.</p><p><b>METHODS</b>This retrospective study included 645 female patients received laparoscopic cholecystectomy or gynecological laparoscopy (laparoscopic oophorocystectomy/myomectomy) between January 2011 and July 2012 in Tongji Hospital. Among them, 207 cases of sufentanil-tramadol patient-controlled intravenous analgesia (PCIA) were enrolled and divided into 2 groups:77 cases in laparoscopic cholecystectomy group, and 130 cases in gynecological laparoscopy group. The pressing frequency and consumption of PCIA, localization and quality of postoperative pain, visual analogue scale (VAS) at 4-6 h, 8-12 h, 18-24 h after surgery, and adverse effect were compared by t-test,χ(2) test, Fisher exact test or Mann-Whitney test.</p><p><b>RESULTS</b>There was no statistical difference of age, body mass index, and operation time between the two groups (all P > 0.05). As compared with the gynecological laparoscopy group (3 (4)), PCIA pressing frequency was higher in the laparoscopic cholecystectomy group (5 (7)), but there was no statistical difference (Z = -1.747, P = 0.081). PCIA consumption in the laparoscopic cholecystectomy group (79 (33) ml) was higher than that in the gynecological laparoscopy group (48 (30) ml) (Z = -6.267, P = 0.000). The postoperative pain localization and quality were different in the two groups, the patients in the laparoscopic cholecystectomy group experienced dull pain in lower abdomen, but the ones in the gynecological laparoscopy group had distending pain in upper abdomen and piercing pain around scapula. The differences of 4-6 h, 8-12 h, 18-24 h VAS scores in the two groups had no statistical significance (all P > 0.05). The total incidence of postoperative adverse effect between the two groups had no statistical significant difference (laparoscopic cholecystectomy group:11.7%, gynecological laparoscopy group:16.2%) (χ(2) = 0.778, P = 0.378). The incidence of dizziness was higher in the gynecological laparoscopy group (6.2%) than that in the laparoscopic cholecystectomy group (0) (Fisher exact test:P < 0.05).</p><p><b>CONCLUSION</b>In the case of sufentanil-tramadol PCIA, laparoscopic cholecystectomy needs more postoperative analgesia, while gynecological laparoscopy has higher incidence of dizziness.</p>

Efficacy analysis of stent angioplasty on symptomatic stenoses of vertebral arteries origins / 中国基层医药

Objective To evaluate the safety and efficiency of endovascular stenting on symptomatic stenosis of vertebral artery origin .Methods 62 patients with symptomatic stenosis of vertebral artery origin received vertebral stenting.Before and after operation ,vascular stenosis rate and clinical symptoms were observed ,and follow-up on all cases.Results The stents was successfully performed in 62 patients.The symptomatic stenosis and clinical symptoms were significantly improved.The stenosis rate decreased from (77.4 ±15.3)%to (12.2 ±6.5)%.The postoperative follow-up lasted for 6-42months.5 cases developed restenosis .Conclusion Endovascular stenting for symptomatic stenosis of vertebral artery origin is safe and effective ,but the long-term curative effect of this technique should be further observed .

Effect of combined treatment with cyclophosphamidum and allicin on neuroblastoma-bearing mice

Objective:To evaluate the efficacy of allicin combined with cyclophosphamide on neuroblastoma (NB)-bearing mice and explore the immunological mechanism in it.Methods:A total of30 NB-bearing mice were equally randomized into model group, cyclophosphamide group and combined therapy group,10 nudemice were set as normal saline(NS) group.Cyclophosphamide group and combined therapy group were weekly injected with60 mg/kg cyclophosphamide for four weeks; besides, combined therapy group was given with allicin(10 mg/kg/d) by gastric perfusion for4 weeks; model group and NS group were given with the same volume of NS.Serum VEGF content was detected byELISA pre-treating(0 d) and on the3rd d,14th d and28th d; on 29th d, all mice were sacrificed and the tumor, liver, spleen and thymic tissues were weighted. Tumors were made into paraffin section for detecting tumor cell apoptosis and proliferation by TUNEL and BrdU method, respectively.Survival curves were drawn byKaplan-Meier method. Results:After treatment, both treatment groups relieved on viscera indexes,VEGF level,T cell subsets distribution and tumor growth and each index of combined therapy group was better than cyclophosphamide group(P<0.05 or0.01); only combined therapy group could significantly increase the lifetime of NB-bearing mice(χ2=5.667,P=0.017).Conclusions:Allicin can improve T cell subsets distribution and inhibitVEGF expression through its immunomodulatory activity, thereby improve the efficiency onNB in coordination with cyclophosphamide.

Preventive effect of zoledronic acid on bone loss around the prosthesis stem after hip replacement / 中国组织工程研究

BACKGROUND:Bone loss to different degrees may appear within 1 year after hip replacement in the femoral or acetabular sides, and severely affect long-term stability of the prosthesis and bone strength. Thus, to reduce bone loss around the prosthesis stem after total hip replacement is significant to prolong the use time of the prosthesis and to prevent fractures surrounding the prosthesis. OBJECTIVE:To observe the preventive effect of zoledronic acid on bone loss surrounding the prosthesis stem after hip replacement. METHODS:A total of 80 patients after total hip replacement in the People’s Hospital of Shenxian from February 2011 to September 2014 were enrol ed in this study. They were divided into two groups (n=40). At 4 days after replacement, patients in the observation group received treatment with zoledronic acid, but those in the control group did not give zoledronic acid. The rest medication was identical between the two groups. Bone mineral density in the hip was measured before replacement and at 1 year after replacement in both groups. Serum calcium and phosphorus levels and alkaline phosphatase activities were observed before replacement, 3 days and 1 year after medication in the two groups. Adverse reaction during medication was recorded in the observation group. RESULTS AND CONCLUSION:The average bone mineral density was significantly decreased in both groups at 1 year after replacement, and significant differences were found as compared with before replacement (P replacement (P0.05). Alkaline phosphatase activities were low in the observation group at 1 year after medication, and significant difference was detected as compared with the control group and that before replacement (P0.05). Within two or three days after medication, nine patients suffered from varying degrees of muscle aches and fever in the observation group, and above symptoms were lessened after taking acetaminophen. These results verify that after total hip replacement, zoledronic acid injection can effectively prevent bone loss around the prosthesis in early stage after replacement, but fever symptoms may occur within a week after replacement. Thus, it is recommended that zoledronic acid injection can be given at 1 week after replacement. If fever and other symptoms appear, acetaminophen can be given.

Effect of different intravenous analgesia methods on postoperative incisional and uterine contraction pain after cesarean section / 中国医师进修杂志

Objective To evaluate the effect of different intravenous analgesia methods on postoperative incisional and uterine contraction pain after cesarean section.Methods Four hundred parturients (ASA Ⅱ-Ⅱ) undergoing cesarean section were randomly allocated into 4 groups,including sufentanil group (group S,96 cases),sufentanil combined with flurbiprofen axetil group (group SK,99 cases),butorphanol group (group N,106 cases) and butorphanol combined with llurbiprofen axetil group (group NK,99 cases).All the parturients received the operation under epidural combined with spinal anesthesia,and received patient-controlled intravenous analgesia (PCIA) after cesarean section.Numerical rating scale (NRS) of postoperative rest and dynamic incisional pain and uterine contraction pain,Ramsay sedation scale (RSS),and PCIA-related adverse events were recorded for 24 h after operation.Results All the parturients were finished this study.The age,body weight,gestational weeks and operative time in 4 groups had no significant difference (P ＞ 0.05).The NRS score of rest incisional pain was equivalent among the 4 groups (P ＞ 0.05).The NRS score of dynamic incisional pain after operative 13 h in group S was significantly lower than that in group N[(3.6 + 1.3) scores vs.(5.4 + 1.2) scores](P＜ 0.05).The NRS score of uterine contraction pain after operative 4,13 h in group N and group SK was lower than that in group S [(1.3 ± 1.0),(1.1 ± 0.9) scores vs.(2.5 ± 1.1) scores and (1.6 ± 1.0),(1.4 ± 0.9) scores vs.(2.9 ± 1.1) scores] (P ＜ 0.05).The RSS scores and incidence rate of dizziness were significantly higher in group N than those in group S (P ＜0.05).No abnormality of new-horn infant was recorded in 4 groups.Conclusion Sufentanil combined with nonsteroidal antiinflammatory drugs can perform effective and safe analgesia on postoperative incisional and uterine contraction pain after cesarean section.

Expression of κ1 opioid receptor and ultrastructure changes in heart atrium from the patients with persistent atria fibrillation / 中华老年医学杂志

Objective To study the effects of persistent atrial fibrillation (AF) on the expression of k1 opioid receptor and change of ultrastructure in heart atrium.Methods The mRNA and protein expressions of κ1 receptor in atrial tissue were detected with RT-PCR and immunochemistry,respectively,in 24 patients with AF and 24 patients with sinus rhythm (SR).Mitochondria were analyzed in the atrial tissue by electron microscopy in 4 patients with AF and 4cases with SR.Results The κ1 receptor mRNA in patients with AF was lower than in patients with SR (262±20 vs.196± 11,P＜0.05),and amount of protein expression was also deduced (1261±90vs.2325± 131,P＜0.05).Mitochondria size was decreased in persistent AF compared with SR[(1.0±0.2) μm vs.(0.8±0.2) μm,P＜0.05].Conclusions The decrease of k1 receptor expression suggests reduction of atrial protective capacity in persistent AF,combining with remodeling of ultrastructure.

Effect of encapsulation in liposomes on toxic effect of bupivacaine on spinal cord in rats / 中华麻醉学杂志

ObjectiveTo study the toxic effect of bupivacaine encapsulated in liposomes on spinal cord in rats.MethodsOne hundred and eight SD rats (200-225 g) in which intrathecal (IT) catheter was successfully implanted without complications were randomly divided into 6 groups ( n =18 each):control group (group C) ; liposome group (group L) ; 0.5％ and 1.0％ bupivacaine groups (groups B1 and B2 ) and 0.5％ and 1.0％ bupivacaine encapsulated in liposomes groups (groups LB1 and LB2 ).In groups L,B1,B2,LB1 and LB2,liposome,0.5 ％ bupivacaine,1.0 ％ bupivacaine,0.5 ％ liposomal bypivacaine and 1.0 ％ liposomal bupivacaine 20 μl were injected IT respectively once a day for 7 consecutive days,while in group C nothing was injected IT.Pain threshold was measured by mechanical stimulation of the plantar surface of hindpaw.Motor function of the hindlimbs was also assessed.The animals were sacrificed at 8 day after IT injection.The lumbar segment of the spinal cord was removed for microscopic examination,detection of neuronal apoptosis (by flow cytometry) and Fos protein expression (by immuno-histochemistry).Results1.0％ bupivacaine IT significantly increased the percentage of apoptotic neurons in group B2 as compared with control group.0.5％ and 1.0％ bupivacaine IT significantly increased the number Fos protein positive cells in group B1 and B2 as compared with group C.1.0％ bupivacaine IT induced severe histologic damage including shrinkage of nucleus and vacuole formation in mitochondria.Encapsulation of bupivacaine in liposomes significantly attenuated bupivacaine-induced increase in apoptosis and Fos protein expression and histologic damage in group LB2 as compared with group B2.ConclusionThe encapsulation in liposomes can decrease the neurotoxicity of 1.0 ％ bupivacaine administered IT in rats.

Clinical effect of perioperative injection of analgecine on patient-controlled intravenous analgesia of fentanyl in lumbotomy patients / 中国基层医药

Objective To compare the effect of perioperative intravenous injection of Analgecine on the analgesic efficacy and complications of patient-controlled intravenous analgesia ( PCIA ) of different doses of fentsnyl in postoperative lumhotomy patients.Methods 200 patients underweat hmbotomy in general anesthesia were randomly divided into four groups with fifty cases each.Fentanyl 1.0mg in group A,fentanyl 0.5mg in group B,fentanyl 1.0mg in group C,fentanyl 0.5mg in group D.The drugs in each group were diluted to 100ml and infused by pumps.Besides,the patients in group C and D were injected with analgecine 3.6u and 7.2u at the night before the operation,preoperation and postoperation respectively.The visual analog scale(VAS),times of PCA and incidence of side effects were recorded during the period of postoperative 24 hours.Results The VAS of group B at 2h after operation was (5.2 ± 1.9 ) points,which was significandy higher than that of group A,C and D( P ＜ 0.05 ),VAS became similar 4h later( P ＞0.05).The demanding times for supplemental bolus in group B were also significantly higher than that of A,C and D( P ＜ 0.05 ).The incidence of nausea,vomiting,itching,somnolence in group B and D were significantly less than those in group A and C( P ＜0.05 ).No respiratory depression or abnormal bleeding occurred in the four groups.Conclusion Perioperative intravenous injection of analgecine had a better effect on PCIA of fentanyl and could reduce fentanyl requirement and its side effects in lumbotomy patients.

Relationship and prognostic study between E-cadherin gene expression and lymphatic hyperplastic reaction in gastric cancer / 肿瘤研究与临床

Objective To study the relationship and prognosis between E-cadherin gene expression and lymphatic hyperplastic reaction in gastric cancer. Methods The degree of lymphocytosis and draining lymph node from 86 cases of gastric cancer were observed and the expression of E-cadherin gene in gastric cancer were detected by SP method of immunohistochemistry (IHC). Results Lymphocyte infiltration degree around gastric cancers was positively related to the reactive hyperplasia of the lymphnodes and was inversely related to lymphatic metastasis. The expression of E-cadherin has relationship with the infiltration degree of stomach carcinoma. To compare with T1/T2 and T3/T4 phases, the result is significantly different (P ＜0.01).Meanwhile, the expression of E-cadherin was positively correlated with tumor-infiltrated lymphocytes and reactive hyperplasia of the lymph nodes, was negatively correlated with lymphatic metastasis in drainage area.Conclusion The over-expression of E-cadherin gene is significantly related to lymphoproliferation and lymph node metastasis. The abnormal expression of E-cadherin can be used as an index to determine prognosis of gastric carcinoma.

Changes of cardiac rhythms in a swine model of adult asphyxial cardiac arrest / 中华急诊医学杂志

Objective To observe the changes of cardiac rhythms in a swine model of adult asphyxia! cardiac arrest. Method Sixteen Pigs were aphyxiated by endotracheal tube clamping until 8 min after loss of aortic pulsations. Resuscitation was then provided and swinds were assigned to received 0.045 mg/kg epinephrine intravenously after 3 min of basic life support. The animals with restoration of spontaneous circulation within 20 min from CPR were defined as successfully resuscitated, while the rest were identified as unresuscitation. Electrocardiogram ( EGG) were monitored from the start of asphyxia to the start of the CPR. Results When loss of pulsations occurred, 2 of 16 animals had ventricular fibrillation; 10 pigs exhibited pulseless electrical activity, and 4 pigs had asystole. During the 8 min after the loss of aortic pulsations, pulseless electrical activity converted to VF in 7 pigs. Immidiatedly prior to resuscitation, VF occurred in 9 pigs, asystole in 4 pigs, and PEA in 3 pigs. Conclusions Most of animals in this swine model of asphyxial cardiac arrest presented PEA, but most of them converted to VF especially late in the asphyxial process.