ABSTRACT
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.
Subject(s)
Humans , Apolipoprotein E4/genetics , Cytosine , Mutation , Blastocyst , Heterozygote , Gene Editing , CRISPR-Cas SystemsABSTRACT
Aim To discuss the effect of Danhong in-jection(DHI) on hyperlipidemia in rats and its possible mechanism. Methods The hyperlipidemia model of rats were induced by high fat diet. The protein expres-sion of adenosine 5'-monophosphate-activated protein kinase(AMPK), p-AMPK, cholesterol-binding ele-ment binding protein (SREBP-1), adenylate-activated protein kinase carboxylasecetyl-CoA(ACC) and p-ACC in liver were detected using Western blot. Results The protein expression levels of AMPK, SREBP-1 and ACC significantly decreased (P<0.05), but the pro-tein expression levels of p-ACC and p-AMPK signifi-cantly increased (P<0.05). Conclusions Danhong injection can reduce the activity of SREBP-1 and ACC by enhancing the activation of AMPK, and effectively reduce the blood lipid level of hyperlipidemic rats by promoting fatty acid oxidation and reducing lipid depo-sition.
ABSTRACT
The paper categories the modern hospital management and finds that there is an important and in-ner-relationship between the paper documents on public hospital reform and the policies on modern hospital manage-ment system construction. Secondly, it seems to be appropriate to coordinate the relation between deepening health reform and social governance in the pathway of modern hospital management system. Hence,this paper puts forward a series of countermeasures to address the difficulties.(1) Scientifically balancing the issues on unification and legaliza-tion with the reform and the system are raised;(2) The introduction of rules and implementation measures are men-tioned;(3) Guideline should be specialized to different hospital properties; (4) Non-public medical sector need more exploration;(5) The adaption and capacity of governance and government transformation are required.
ABSTRACT
There ass an urgent call for the dynamic medical service price-adjustment mechanism with the fully launched Zero Markup policy,however it was lacking of one unified coordination mechanism between departments.It analyzed the responsibilities and challenges of four departments(Health,Pricing,Health Insurance and Finance Department).Also,one theoretical model has been established for analyzing the impacts on the four departments by the scope of pricing-adjustment.By witnessed the evidences on the price-adjustment,it highly recommended that the strategy for price-adjustment should go with high frequency but in a minor change.Meanwhile,it also proposed that to build one well-coordinated mechanism,introduce third parties to involve,and establish one simulation system for price-adjustment to push forward the progress of dynamic price-adjustment mechanism.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical outcomes of anterior corpectomy combined with anterior intervertebral decompression and fusion for multilevel cervical spondylotic myelopathy.</p><p><b>METHODS</b>The clinical data of 28 patients with multilevel cervical spondylotic myelopathy who underwent surgery from October 2012 to June 2014 were retrospectively analyzed. There were 18 males and 10 females, aged from 45 to 77 years old with an average of (60.11±9.37) years. Three levels were involved in 27 cases, while four levels were involved in 1 case. The preoperative JOA score was 8.89±1.87; the fusion segments angles was (4.87±4.56)°; and the cervical curvature was (11.68±1.25)°. Anterior hybrid decompression and fusion were performed in 28 patients. The fusion segments angles and the cervical curvature were assessed by X-rays at 1, 12 months after operation, respectively. JOA score was used to evaluate the clinical effect.</p><p><b>RESULTS</b>The operative time was 163 min on average (ranged from 120 to 205 min), and intraoperative bleeding was 198 ml on average(ranged from 100 to 300 ml). Hoarseness occurred in 1 case and got recovery at 3 weeks after operation and choke cough occurred in 1 case, and got improvement at 1 week after operation. All the patients were regularly followed for 12-24 months with an average of(18.46±3.20) months. Graft bone obtained fusion at 12 months after operation and the position of internal fixation was good. The fusion segments angles, the cervical curvature and JOA scores were significantly improved at 1, 12 months after operation(<0.05). The improvement rate of JOA score was(46.46±20.26)% at 12 months after operation, 12 cases got excellent results, 14 good and 2 fair.</p><p><b>CONCLUSIONS</b>Anterior corpectomy combined with anterior intervertebral decompression and fusion is safe and effective and can get satisfactory effects for multilevel cervical spondylotic myelopathy.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To compare the short-term efficacy of anterior cervical discectomy and fusion(ACDF) with traditional nail plate system and Zero-profile device in the treatment of cervical spondylotic myelopathy(CSM).</p><p><b>METHODS</b>The clinical data of 45 patients with CSM treated from July 2014 to August 2015 was retrospectively analyzed. There were 23 males and 22 females with an average age of 53.7 years old(range, 32 to 71 years old). The course of disease was 5 months to 2 years. All the patients were treated with ACDF with 24 cases by traditional nail plate system fixation(group A) and 21 cases by Zero-P system fixation(group B). Operation time and intraoperative bleeding were compared between two groups. Neurological function and cervical pain were evaluated by Japanese Orthopaedic Association scores (JOA) and visual analogue scale (VAS), respectively. Cervical curvature(Cobb angle) change and intervertebral fusion were evaluated by X-rays and CT. And associated complications were analyzed in two groups.</p><p><b>RESULTS</b>All the patients were followed up for 12 to 16 months with an average of 14 months. Operation time of group A and B was(87.6±23.2) min and (62.7±17.3) min respectively, and the difference was significant between two groups; and intraoperative bleeding was (80.2±36.8) ml and (78.4±29.6) ml respectively, and the difference was not significant. At final follow-up, JOA and VAS of all patients were obvious improved, but there was no significant difference between two groups. Preoperative Cobb angle in group A and B was (8.7±4.3) ° and (8.6±4.2) ° respectively, and the difference was significant. The Cobb angle at final follow-up was (14.5±6.4) ° and (17.4±8.6) ° respectively, and the difference between two groups was significant. The incidence of dysphagia in group A and B were 29.17% and 9.52% respectively, and there was significant difference between two groups. All intervertebral spaces got fusion at final follow-up. No tracheo-asophageal injury and recurrent laryngeal nerve damage or other complications were found. No fusional migration, subsidence, loosening, breakage, etc. were found.</p><p><b>CONCLUSIONS</b>The clinical comparison of Zero-P interbody fixation system and cervical plate internal fixation for the treatment of cervical spondylosis was quite fair, but Zero-P showed a better therapeutic effect with improvement of life quality.</p>
ABSTRACT
Erythroderma with complicated etiology is one of the severe skin diseases and has high mortality,of which the incidence was 0.5％-1.5％ in skin diseases.Erythrodermic psoriasis (EP) is the commonest type of erythroderma.In addition,there are drug-induced erythroderma,erythroderma secondary to preexisting dermatoses,malignancy-related erythroderma,and idiopathic erythroderma of unknown etiology.Erythroderma of different etiologies has various clinical manifestations,resulting in relevant curative effects and outcomes.In this article,we retrospectively investigated 205 erythroderma patients about clinical symptoms,auxiliary examination and treatments,and evaluated the efficacy and prognosis.There were 84 cases of EP among 205 patients,10 cases of erythroderma caused by specific drugs,77 cases of erythroderma secondary to preexisting dermatoses (excluding psoriasis),7 cases of erythroderma patients suffering from malignancy and 27 cases with unknown causes.We concluded that the etiology of male patients in different age groups had significant difference.The incidence of EP was the highest among all types.The EP was commonly accompanied with hypoproteinemia,and changed into psoriasis vulgaris after treatment.Drug-induced erythroderma was commonly accompanied with fever,and mostly cured by systematic steroid therapy.For erythroderma secondary to preexisting der matoses,the original dermatoses must be actively treated to achieve a satisfying prognosis.Erythroderma with malignancy or unknown causes had long-term duration,poor response to the treatment,and high potential to relapse.Therefore,clarifying the etiology,providing an appropiate and individual regimen,and regular follow-up are crucial for the successful treatment of erythroderma with unknown causes.
ABSTRACT
Objective To explore the advantages of Argus method by comparing the accuracy and timeliness of Argus and artificial methods for measuring femoral head necrosis area in MRI scanning.Methods Totally 17 patients (31 hips) were measured with Argus and artificial methods respectively for the necrosis area, and then the measuring results and time were compared, and the correlation was investigated between the results and the patients' pain degree, along with that between the results and the extent of femoral head collapse.Results The necrosis area ratios determined by Argus and artificial methods were (33.5±4.08)%and (34.6±4.06)%respectively, with no statistical difference between the ratios (P>0.05). The time consumed by artificial method was (21.3 ±3.62)min, significantly longer than (7.89 ±1.03)min by Argus method, with P<0.001. Regression analysis proved that the necrosis areas were positively correlated with the patients' pain degree, and the correlation coefficient by Argus method was 0.807 8, more than 0.740 9 by artificial method. The femoral heads of 11 cases(16 hips) collapsed in the follow-up period, the necrosis areas were positively correlated with the patients collapse level, but the correlation coefficient by Argus method was 0.783 8, more than 0.726 7 by artificial method.Conclusion Argus method gains high accuracy and timeliness when used in MRI scanning of femoral head necrosis area, and thus is worth popularizing clinically.
ABSTRACT
Objective To assess the surgical outcomes of double-level isthmic spondylolisthesis in adults. Methods From Mar. 2006 to Nov. 2010, 30 patients with double-level lumbar isthmic spondylolisthesis were treated with modified Jaslow technique combined with posterior lumbar interbody fusion. Clinical outcomes were assessed by Japanese Orthopedic Association (JOA) score; the functional disability was quantified by Oswestry Disability Index (ODI); the Lenke grading system was used to assess the spinal fusion; and theHenderson grading system, the intervertebral height index, and the Taillard index were used to assess the clinical outcome. Results All the 30 patients achieved reduction of different degrees, with the mean reduction rate being (43. 60±25. 29) %. The intervertebral height index was (17. 68±6. 67)% before operation, increased to (50. 99 ± 4. 94) % at 1 week after operation and (44. 37 ±5. 84) % at the last follow-up. The Taillard index was (20. 91 ± 7. 11) % before operation, (10. 23 ± 2. 16) % at1 week after operation, and (11. 87±2. 73) % at the last follow-up. The height index and the Taillard index before operation were significantly different from those of the other two time points (1 week after operation and final follow-up, P<0. 01). The bone fusion was grade A in 49 levels and grade B in 11 levels. The JOA score increased from 9. 60 ± 1. 89 before operation to 22. 40±2. 06 at 6 months after operation and 22. 70±1. 63 at the final follow-up. ODI was 34. 90±5. 56 before operation, which was decreased to 11. 80±1. 81 at 6 months after operation and 10. 70±1. 33 at the last follow-up. The JOA score and the ODI index before operation were significantly different from those of 6 months after operation and those at the final follow-up (P<0. 01). The Henderson clinical outcome was excellent in 19 cases, good in 8 cases, and poor in 3 cases. Conclusion Complete decompression, reduction of isthmic spondylolisthesis by modified Jaslow technique, pedicle screw fixation, and posterior lumbar interbody fusion can achieve satisfactory clinical results for adults with double-level isthmic spondylolisthesis.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of polyethylene oxide (PEO) on microcirculation of normal rat hindlimb skeletal muscle.</p><p><b>METHODS</b>Sixteen male Wistar rats were anesthetized and equally and randomly divided into PEO group (administered with 10 ppm PEO solution) and control group (administered with equal volume of normal saline). The PEO solution or saline was separately injected through the caudal vein at a constant rate of 5 ml/h for 20 minutes. Using short axis view at right mid thigh region, contrast-enhanced ultrasonography was performed before and after the administration of solution. Electrocardiogram, blood pressure, and central venous pressure were also monitored.</p><p><b>RESULTS</b>In the PEO group, after the administration of PEO, microcirculation capillary volume increased from (20.78±2.63) dB to (22.40±1.94) dB (P=0.023), red blood cell velocity from (0.27±0.08) s-1 to (0.35±0.13) s-1(P=0.010), and capillary blood flow from (5.65±1.81) dB/s to (7.91±3.28) dB/s (P=0.013). In the control group, there were no significant changes in microcirculation capillary volume, red blood cell velocity, and capillary blood flow (all Pþ0.05) after the injection of normal saline. The changes of heart rates, blood pressures and central venous pressure were not significant after the administration of either PEO or saline (all Pþ0.05).</p><p><b>CONCLUSION</b>PEO can remarkably increase capillary volume, red blood cell velocity, and capillary blood flow in normal rat hindlimb skeletal muscle.</p>
Subject(s)
Animals , Male , Rats , Hindlimb , Microcirculation , Muscle, Skeletal , Polyethylene Glycols , Pharmacology , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To investigate the method for preventing the postoperative nausea and vomiting (PONV) after laparoscopic gynecologic surgery.</p><p><b>METHODS</b>One hundred and twenty patients being for laparoscopic gynecologic surgery at I- II grade as American Society of anesthesiologists (ASA) were randomly divided into three groups, 40 cases in each group. Twenty minutes before the operation, the mixture of 2. 5 mg Droperidol (1 mL) and 1 mL 0. 9% sodium chloride solution was injected into the bilateral Neiguan (PC 6) in group I , and an intravenous injection with 1 mL Droperidol was used in group II , while there was no treatment carried out in group Ill'. Twenty four hours after the operation, the frequency and degree of nausea and vomiting were observed and scored according to the criteria standard.</p><p><b>RESULTS</b>The incidence rate of nausea was 10. 0% (4/40) in group I , 57. 5% (23/40) in group II , which was significantly different from 80. 0% (32/40) in group III (P<0. 01, P<0. 05, respectively), while it was lower in group I than in group II (P<0. 01). The incidence rate of vomiting was 7. 5% (3/40) in group I , 52. 5% (21/40) in group II , which was significantly different from 75.0% (30/40) in group III (P<0.01, P<0.05 respectively), while it was lower in group I than in group II (P<0.01). No complication, such as obvious drowsiness, anxiety and extracorticospinal tract reaction, was observed among the three groups.</p><p><b>CONCLUSION</b>Acupoint injection at Neiguan (PC 6) with a small dose of Droperidol can effectively prevent the PONV after laparoscopic gynecologic surgery without other adverse effects.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Young Adult , Acupuncture Points , Droperidol , Gynecologic Surgical Procedures , Injections , Laparoscopy , Postoperative Nausea and Vomiting , Drug TherapyABSTRACT
@#ObjectiveTo explore the effect of sustained spinal cord compression on spinal cord injury (SCI).MethodsTwenty four dogs underwent sustained spinal cord compression for 30 minutes (group A), 90 minutes (group B) and 180 min (group C) with a device designed by the authors for weight loading spinal compression, and anthor four dogs as the control group (group D) only underwent surgical operation without SCI. Cortex somatosensory evoked potentials (CSEP) were monitored during all the procedure of making model. The changes of pathologic histology, imaging and behavior examination of all animals were observed.ResultsThe lesion degrees gradually increased from group A to group C (P<0.01), and there was similar outcome in MRI imaging. The behavior improvement in group A was more significantly than that in groups B and C (P<0.05).ConclusionSustained spinal cord compression aggravates the extent of SCI process, and the decompression must be taken as soon as possible.
ABSTRACT
Amylum can be transformed into trehalose on the action of the MTSase and MTHase, however, the percentage of transformation is low. The research on the enzyme immobilization through four kinds of immobilization carrier is described in this paper. The result shows that the carriers, which are put into with enzyme liquid and crossbonded with chi-tosan and glutaraldehyde at first, can adsorb many enzymes independent from this process of trehalose synthesizing, consequently, the enzyme activity is increased sharply. By comparing with the influence of the immobilizing process and some factors in the reaction conditions, such optimize condition can be reached: the time for carrier crossbonding with glutaraldehyde is 18hours , the time with enzyme is another 18hours , and the time of reaction with amylum (10%) is 9hours.The result of the content of trehalose can reach 27.22g/L and the percentage of transformation can reach 54.43% , which previously is 2.67g/L and 5.33% respectively before dealt with by carriers.