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Objective To investigate the protective effect of berberine (BBR) against ionizing radiation injury in rats and its mechanism of action. Methods Sprague-Dawley rats were divided into seven groups: normal control group, 1-Gy radiation group, 1-Gy radiation plus low-dose BBR (50 mg/kg) group, 1-Gy radiation plus high-dose BBR (150 mg/kg) group, 3-Gy radiation group, 3-Gy radiation plus low-dose BBR (50 mg/kg) group, and 3-Gy radiation plus high-dose BBR (150 mg/kg) group. All the groups except the normal control group were exposed to external irradiation with a medical electron linear accelerator, followed by BBR administration by gavage for consecutive ten days. The serum levels of superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) were measured by using the micromethod. The pathological changes of the bone marrow and small intestine were observed with HE staining. Results Compared with the normal control group, the radiation groups showed significantly increased MDA levels (P < 0.05), significantly decreased SOD and GSH levels (P < 0.05), and more severe pathological damage of the bone marrow and small intestine. Compared with the radiation groups, the BBR groups showed significantly decreased MDA levels (P < 0.05), significantly increased SOD and GSH levels (P < 0.05), and reduced pathological damage to the bone marrow and small intestine, which were more marked in the high-dose BBR group. Conclusion BBR has a certain protective effect against radiation injury in rats, which may be through increasing the activity of antioxidant substances, enhancing free radical clearance, and thereby alleviating free radicals-caused oxidative damage.
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@#During the new coronavirus disease 2019 (COVID-19) pandemic, there has been controversy over whether emergency surgical management should be performed or not in the patients with COVID-19. Stanford type A aortic dissection is a very urgent life-threatening disease, and guidelines recommend surgical treatment for patients with type A aortic dissection in the first instance. However, intraoperative extracorporeal circulation can be fatal to patients recovering from COVID-19. During the pandemic, extracorporeal membrane oxygenation (ECMO) has played an important role in supporting COVID-19 patients with acute respiratory failure. This article reports a successful V-V ECMO treatment for a Stanford type A aortic dissection patient, who suffered respiratory failure caused by COVID-19 after emergency surgery.
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Objective:To investigate the clinical manifestations, pathogenesis,diagnosis and treatment of negative pressure hydrocephalus (NPH).Methods:A retrospective analysis was performed on the 5 patients with NPH admitted to the Department of Neurosurgery, Tianjin Huanhu Hospital from January 2019 to December 2021. All of the patients underwent lumbar puncture and ventricular puncture to test the pressure. Three patients underwent endoscopic third ventriculostomy (ETV), the outcome of the patients was observed.Results:The pressure of subarachnoid was not equal to intraventricular, and the pressure of intraventricular was negative. Cisternography showed cerebrospinal fluid circulation obstruction in all 5 cases. The symptoms of 1 patient were improved after external negative pressure drainage, 3 patients were improved after further ETV and 1 patient had pulmonary infection without further surgical treatment.Conclusion:With the obstruction of cerebrospinal fluid circulation, the pressure of lateral ventricle and subarachnoid is different, when the pressure of brain or subarachnoid drop, the ventricular expansion under the effect of pressure gradient, intraventricular pressure drop even for the negative pressure. CT cisternography provides strong evidence for the diagnosis of this disease. External ventricular drainage with negative pressure and ETV are effective treatment methods.
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Objective:To analyze the application value of metagenomic next-generation sequencing (mNGS) in the detection of pathogenic bacteria in brain abscesses.Methods:The data of patients with brain abscess in Tianjin Huanhu Hospital from January 2019 to December 2021 were retrospectively analyzed. All patients underwent stereotaxic abscess puncture and drainage. According to the different methods of pathogen detection, they were divided into bacterial culture group (bacterial culture only) and mNGS group (bacterial culture with mNGS). The clinical symptoms, abscess site, bacterial culture and mNGS results, antibiotic application protocol and prognosis of the patients were analyzed. The bacterial detection results of the two groups were analyzed, and the antibiotic application and prognosis were compared. χ 2 test, exact probability method and Mann Whitney test were used to compare the difference between the two groups. Results:A total of 43 patients with brain abscess were enrolled, including 21 cases in bacterial culture group and 22 cases in mNGS group. The positive rate of bacteria culture group was 42.9% (9/21), the positive rate of bacteria culture group was 45.5% (10/22), and the positive rate of mNGS detection was 100% (22/22). Only 3 cases in the bacterial culture group could have a clear bacterial source, while 17 cases in the mNGS group could have a clear bacterial source according to the bacterial results, showing a significant statistical difference between the two groups (χ 2=19.69, P<0.001). The return time of bacterial culture was 7.0 (4.0,7.0) days, and the average return time of mNGS was 1.5 (1.5,1.5) days, the difference of bacterial return time between the two groups was statistically significant ( Z=0.00, P<0.001). The cost of antibiotic use in bacterial culture group was 24.00 (5.60,31.00) thousands yuan, and the cost of antibiotic use in mNGS group was 12.00 (2.10, 20.00) thousands yuan, and there was significant statistical difference between them ( Z=5.22, P=0.026). Conclusions:MNGS can quickly and accurately identify the types and sources of brain abscess pathogens, guide the clinical application of antibiotics more targeted, reduce the cost of antibiotic use, and is an effective method for the detection of brain abscess pathogenic bacteria.
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@#As an extracorporeal life support technology, veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been demonstrated its role in the treatment of patients with severe respiratory failure. Its main advantages include the ability to maintain adequate oxygenation and remove excess CO2, increase oxygen delivery, improve tissue perfusion and metabolism, and implement lung protection strategies. Clinicians should accurately assess and identify the patient's condition, timely and accurately carry out VV-ECMO operation and management. This article will review the patient selection, cannulation strategy, anticoagulation, clinical management and weaning involved in the application of VV-ECMO.
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@#Objective To explore the early outcomes of the surgical treatment for patent ductus arteriosus (PDA) combined with intracardiac abnormities via right vertical infra-axillary thoracotomy (RVIAT). Methods A total of 7 children with PDA combined with intracardiac defects underwent surgery through RVIAT at the Second Affiliated Hospital of Nanjing Medical University from 2016 to 2018. There were 4 males and 3 females, with an average age of 5.3±4.5 years and weight of 18.0±11.2 kg. Results In all patients, PDA was ligated before the repair of intracardiac abnormities. No patient died in hospital. All patients were followed up, with a mean follow-up time of 18.0±8.0 months. No other complications such as residual shunts, arrhythmias, hemorrhaging or wound infection occurred after operations or during the follow-up period. Conclusion RVIAT is an emerging technique used for the surgical repair of PDA combined with intracardiac defects. It yields satisfying cosmetic results, without increasing postoperative complications or mortality.
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OBJECTIVE：To prepare Brevisc apine（BRE） nanocrystals，and to evaluate its quality. METHODS ：BRE nanocrystal suspensions were prepared by media milling method. The diameter and amount of grinding beads ，grinding time ，type and ratio of stabilizer ，BRE ratio were investigated to screen the optimal technology and formulation with particle size and polydispersity index （PDI） as evaluation indexes. Using morphology ，color，particle size and PDI of BRE nanocrystals as evaluation index ，different lyoprotectants （50％ mannitol，5％ glucose，5％ lactose）and without lyoprotectant were investigated to screen the optimal lyoprotectant. Particle size analyzer ，scanning electron microscope （SEM），X-Ray diffraction （XRPD）， differential scanning calorimeter （DSC）were used to evaluate the quality of BRE nanocrystals which was prepared with the optimal technology and formulation. RESULTS ：The optimal technology and formulation of BRE nanocrystals included that particle size of 0.6 mm zirconia beads with the amount of 450 g，grinding time of 1 h，stabilizer of 15％ Tween-80，BRE ratio of 25％，without lyoprotectant. Prepared BRE nanocrystals were yellow powder with loose texture and uniform color. The average particle size of BRE nanocrystals was （283.10±3.08）nm，average PDI was （0.212±0.021）and average Zeta potential was （－38.48±0.39）mV. BRE nanocrystals were rod-like crystals ，uniform in distribution and had no change in crystalline state. Accumulative dissolution of BRE nanocrystals were （90.37±1.22）％ within 20 min. Under the condition of （40±2）℃ temperature and （75±5）％ relative humidity，BRE nanocrystals remained stable after being kept away from light for 3 months. CONCLUSIONS ：Established preparation method of BRE nanocrystals is simple and feasible. Prepared BRE nanocrystals show good stablility and dissolution.
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Despite the improvements in the diagnosis and management during the past six decades, acute aortic dissection (AAD) remains a life-threatening condition associated with significant morbidity and mortality rates. Due to the relatively rare occurrence of AAD, several clinical registries have been established to gain insights into this lethal disease in a large number of patients, such as the International Registry of Acute Aortic Dissection (IRAD), the German Registry for Acute Aortic Dissection Type A (GERAADA), and the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database Aortic Section. This review aims to interpret and compare the latest results of the IRAD, STS and GERAADA database. It focuses on several controversial and key issues in the diagnosis and management of acute aortic dissection in hope of providing some insights and references for cardiovascular professionals engaged in the care of this deadly disease.
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Colorectal cancer is one of the most common malignant tumors worldwide. Surgical resection is the most important and decisive method in the treatment of rectal cancer. Total mesorectal excision (TME) has greatly reduced the local recurrence rate of middle and low rectal cancer. However, local recurrence and distant metastasis remain the leading cause of death in patients with rectal cancer. 5-fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy has been widely accepted in locally advanced rectal cancer and was recommended by various clinical practice guidelines as the standard treatment option. Tumors often achieve satisfactory reduced stage after neoadjuvant radiotherapy, and some patients even achieve pathological complete regression, which brings much controversies to the choice of adjuvant chemotherapy. This article intends to introduce evidence-based evidences for adjuvant chemotherapy for rectal cancer, impact of current neoadjuvant models on choice of adjuvant chemotherapy strategies, controversies and considerations for adjuvant chemotherapy in the context of neoadjuvant radiotherapy.
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Clinical data of 85 patients with breast abscess during lactation treated in our hospital from January 2014 to October 2017 were retrospectively analyzed.Among 85 cases,30 patients received traditional abscess incision drainage,35 received needle aspiration,and 20 received negative pressure drainage with small incision.The pus culture findings,average hospitalization expenses,average treatment time,pain score,postoperative breast appearance were evaluated.The pus culture found 24 cases of staphylococcus aureus infection in 85 cases (28％),including 40 cases of Methicillin resistant Staphylococcus aureus (47％).The proportion of central abscess (14/20) in patients with small incision drainage was significantly higher than that of patients with needle aspiration treatment (4/35) (P＜0.05).The average hospitalization expense of the puncture group was significantly lower than that of other two groups (P＜0.01).The average treatment time of abscess incision drainage group was significantly higher than that of other two groups (P＜0.01),and the recovery time was all longer 1 month.The score of pain in the abscess incision drainage group was significantly higher than that in other two groups (P＜0.01),and all patients had moderate to severe pain.The breast shape satisfaction of abscess incision drainage group was significantly lower than that of other two groups (P＜0.01).The analysis indicates that treatment of breast abscess during lactation with needle aspiration and negative pressure drainage has short treatment time,no scars and less pain;and it is suggested that central abscess may be treated early with negative pressure drainage.
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Acute aortic dissection (AAD) is a potentially catastrophic cardiovascular disease,with significant morbidity and mortality,and it remains a challenge to diagnose and treat.Survival rate has been shown to be directly related to prompt diagnosis and precise management,it is necessary for early diagnosis and treatment.However,diagnosis of the disease relies heavily on various imaging techniques,remaining time-consuming and difficult to obtain.Nevertheless,the application of biomarkers provides a new direction for the diagnosis of AAD.Therefore,the application of biomarkers with high specificity and sensitivity contribute to optimal treatment to reduce the mortality rate is the current research direction.This article was to summarize the domestic and abroad research advances which focused on the biomarkers and progress of aortic dissection.
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Controversy remains on how to manage left colic artery (LCA) when it comes to laparoscopic proctectomy. With regard to the level of detachment, a high tie of inferior mesenteric artery (IMA) is meant as a ligation at the origin of aorta, while the low tie is the ligation of IMA below the initiation part of left colic artery which is left. Several key points of LCA preservation, including clinical value, oncologic safety and the difficulty of operation, have always been debated. Some scholars hold the point of view that the preservation of LCA will hamper the lymph nodes dissection around the inferior mesenteric artery, resulting in incorrect pathological staging and dismal outcome. Of note, low tie prolongs the duration of operation and increases the anastomotic tension. However, increasing research results have established its clinical values. The value for reducing the risk of anastomotic leakage and the effect on the lymph nodes dissection at the root of inferior mesenteric artery will be discussed based on previous studies and our clinical practice. We came up with a novel concept of "the lymph nodes in the triangular domain of inferior mesenteric artery which consists of abdominal aorta, inferior mesenteric vein(IMV)/LCA and IMA" instead of traditional No.235 lymph nodes. In our innovative approach of total mesorectal excision guided by vessel, a crack was made at the root of aorta and the dissection was performed along IMA, reaching the origin of LCA. The lymph nodes will be harvested as a whole. After achieving process standardization, vessel-oriented approach and left colic artery preservation makes this region susceptible to lymphadenectomy, protecting submesenteric plexus and guarantying the oncological safety without increasing operative difficulty.
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Humans , Laparoscopy , Ligation , Lymph Node Excision , Mesenteric Artery, Inferior , General Surgery , Rectal Neoplasms , General SurgeryABSTRACT
<p><b>OBJECTIVE</b>To investigate the impact of the weekday of surgery on the prognosis of patients with colorectal cancer.</p><p><b>METHODS</b>A retrospective analysis was conducted in patients with colorectal cancer who underwent radical resection in Fudan University Shanghai Cancer Center(FUSCC) between January 2007 and December 2013, and 4 971 patients were identified eligible. Statistical analyses were carried out between patients who received surgery on Monday to Thursday and those who received surgery on Friday. Chi-square test was used to analyze the relationship between clinicopathological parameters and day of surgery. T test was used to compare continuous variables between groups. The 5-year overall survival (OS) and disease-free survival (DFS) were calculated by the Kaplan-Meier method, and compared by log-rank test.</p><p><b>RESULTS</b>There were no statistically significant differences between two groups in age, gender and pathological grade et al (all P>0.05). However, the number of dissected lymph node was higher in patients who received surgery on Monday to Thursday (median 16) compared with patients who received surgery on Friday (median 14), with statistically significant difference (P=0.038). The 5-year OS and DFS in all eligible patients were 78.0% and 55.0%, respectively. 5-year OS of patients in Monday to Thursday surgery group and Friday surgery group was 79.6% and 77.2%, while 5-year DFS in two groups was 57.8% and 50.4%. There were no significant differences in OS and DFS between two group, with P=0.882 and P=0.210, respectively. Subgroup analyses were conducted according to different pathological stages. 5-year OS of patients at stage I( in Monday to Thursday surgery group and Friday surgery group was 94.7% and 90.6% (P=0.742) and 5-year DFS was 85.1% and 78.2% (P=0.765). 5-year OS of patients at stage II( in two groups was 85.5% and 83.7% (P=0.496) and 5-year DFS was 72.7% and 62.8% (P=0.121). 5-year OS of patients at stage III( in two groups was 69.7% and 69.4%(P=0.354) and 5-year DFS was 41.8% and 37.4% (P=0.976). No statistically significant differences manifested in subgroup analyses.</p><p><b>CONCLUSION</b>Patients with colorectal cancer undergoing surgery on Monday to Thursday have similar long-term prognosis with those on Friday.</p>
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Adult , Female , Humans , Male , Middle Aged , China , Colorectal Neoplasms , General Surgery , Disease-Free Survival , Lymph Node Excision , Neoplasm Staging , Prognosis , Retrospective Studies , Time FactorsABSTRACT
Objective The purpose of this study was to explore the risk factors of recurrence of atrial fibrillation (AF) after surgical radiofrequency ablation in patients undergoing cardiac valve surgery.Metbods Retrospective analysis was made in 255 cardiac valve patients undergoing concomitant radiofrequency modified Maze operation from April 2010 to December 2012 in Nanjing Drum Tower Hospital.Multivariate logistic regression analysis was used to screen independent risk factors for predicting recurrence of AF.Results Excluding 8 patients died after surgery,11 cases who were junctional rhythm after ablation or received pacemaker implantation and 60 lost case,176 patients were finished follow-up.107 cases maintained stable sinus rhythm (SR),whereas other 69 cases developed AF recurrence.Multivariate logistic regression analysis found larger left atrial size,higher B-type natriuretic peptide,lower preoperative heart rate and postoperative AF rhythm before discharge were independent risk factors for predicting AF recurrence.Conclusion Larger left atrial size,higher B-type natriuretic peptide and lower preoperative heart rate before surgery can impact outcome of surgical radiofrequency ablation in patients undergoing cardiac valve surgery after following 12(4-38)months.They can be used in clinical practice to choose more suitable cardiac valve patients with AF for surgical ablation.Postoperative appearance of AF rhythm before discharge indicated a poor prognosis,which should be interfered with drugs or electrical cardioversion.
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Objective:To prepare capsaicin liposomes and study the feasibility by in vitro percutaneous penetration test. Meth-ods:Capsaicin liposomes were prepared by a film-ultrasonic method. The best formula was screened by orthogonal test based on single factor studies with the entrapment efficiency as the index. The improved Franz diffusion cells were used to study the transdermal pene-tration of capsaicin suspensions, capsaicin liposomes and capsaicin ointments, and the cumulative penetration amount through the isola-ted rat skin was compared. Results:The optimal formula of capsaicin liposomes were as follows:the ratio of capsaicin to lipids was 1∶5;the amount of Tween-80 was 100 mg;the amount of vitamin E was 50 mg;10 ml dichloromethane was used as the solvent. The op-timal pH value of the external phase was 6. 5 with the volume of 10 ml. The ultrasonic time was 8 min. The order of 12-hour cumulative penetration amount was capsaicin liposomes>capsaicin-PBS suspensions>capsaicin ointments. Capsaicin liposomes had the highest 12-hour cumulative penetration amount and showed obvious sustained-release property. Conclusion:Capsaicin liposomes have high en-trapment efficiency, good percutaneous penetration and sustained-release property, and the preparation technology is simple.
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Objective To prepare nifedipine( NF)sustained-release pellet tablets,and study of its release behavior in vitro. Methods Soluplus was selected as a carrier to prepare solid dispersion of NF by hot melt extrusion technique( HME), and the ratio of the drug to carrier was 1:1. The samples were validated as the solid dispersion by differential scanning calorimetry(DSC). Extrusion-spheronization technique was introduced to prepare NF pellets and EudragitRS 30D was used as the coating material. The NF sustained-release tablets were prepared by direct compression of the coated pellets and suitable excipients. Results The release data in vitro proved that the drug release from the tablets was steady and complete over 24 hours. Conclusion The release of NF from sustained-release tablets is slow and steady. The method is easy to operate. The in vitro drug release pattern follows first-order kinetics.
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Objective To analyze the clinicopathological factors impacting on the prognosis of colorectal cancer liver metastases and to investigate how to improve patients' survival.Methods The clinical data of 103 patients who received radical resection for liver metastases from colorectal cancer from January 2005 to December 2011 were enrolled.The survival curve was drawn by Kaplan-Meier method,and the survival rates were analyzed by Log-rank test.Factors influencing survival were analyzed by Cox regression model.Results All patients were followed up from 10 to 60 months,The 1-,3-,5-year's survival rates were 90％,49％,39％,respectively.Univariate analysis revealed that number and size of liver metastases,distribution of liver metastases,serum CEA concentration,complications,postoperative chemotherapy were related to prognosis (x2 =24.732,9.461,9.568,25.948,25.370,5.701,P ＜ 0.05).Multivariate analysis identified number of liver metastases,serum CEA concentration,complications were as significant predictors of survival (Wald =7.974,12.051,11.547,P ＜ 0.05).Conclusions Number of liver metastases,serum CEA concentration,complication are important prognostic factors for liver metastases from colorectal cancer.Appropriate expansion of surgical indication,early diagnosis with intensive follow-up is crucial to increase the survival rate after hepatectomy for liver metastasis of coloractal carcinoma.
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Objective To investigate the value of modified loop ileostomy in laparoscopic low and superlow radical resection of the rectal cancer with reservation of anus.Methods The clinical data of 108 patients who received laparoscopic low and super-low radical resection of rectal cancer with preservation of anus at the Subei Hospital of Jiangsu Province from January 2010 to June 2012 were retrospectively analyzed.Fifty-three patients who received preventive ileostomy were in the ileostomy group,and 55 patients who did not receive preventive ileostomy were in the non-ileostomy group.The operation,incidence of complication and follow-up of the 2 groups were analyzed.All data were analyzed using the t test,chi-square text or Fisher exact test.Results The operation time and blood loss were (185 ± 14)minutes and (31 ± 26)ml in the ileostomy group,and (154 ± 12)minutes and (28 ± 19)ml in the non-ileostomy group,with no significant difference between the 2 groups (t =2.34,1.82,P ＞ 0.05).The time to first flatus,time to liquid diet intake,time to pelvic drainage tube removal,duration of hospital stay,hospital costs were (1.1 ± 0.3) days,(1.1 ± 0.2) days,(5.2 ± 1.0) days,(7.2 ± 1.4) days,(3.0 ± 0.2) ×104 yuan in the ileostomy group,and (4.2 ± 0.6) days,(4.3 ± 0.6) days,(8.4 ± 3.9) days,(12.9 ±4.4)days,(3.8 ±0.7) × 104 yuan in the non-ileostomy group,with significant differences between the 2 groups (t =7.25,28.12,15.34,34.01,7.83,P ＜ 0.05).The incidences of postoperative complications and anastomotic fistula were 5.7％ (3/53) and 0 in the ileostomy group,and 21.8％ (12/55) and 12.7％ (7/55) in the non-ileostomy group,with significant differences between the 2 groups (P ＜ 0.05).Conclusion Modified loop ileostomy in laparoscopic low and super-low radical resection of rectal cancer can effectively reduce the incidence of anastomotic fistula,and helps the recovery of patients.
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Objective To compare the complications of temporary ileostomy and temporary colostomy for colorectal anastomoses,then to evaluate which one is superior to another.Methods Studies and relevant literatures comparing temporary ileostomy with temporary colostomy for defunctioning colorectal anastomoses were searched though PubMed,Embase and the Cochrane Library.The rates of complications were pooled and compared using a meta-analysis.The risk ratios were calculated with 95％ confidence intervals to evaluate the safety and efficacy of each technique.Results Five randomized controlled trials and seven non-randomized studies were included,with 1687 patients in total.The meta-analysis of the RCTs demonstrated a lower risk of stoma prolapse ( Risk ratio 0.15) in the temporary ileostomy group.Meta-analysis of the non-randomized studies showed a lower risk of stoma prolapse ( Risk ratio 0.26) and wound infection after stoma closure ( Risk ratio 0.28 ) in the temporary ileostomy group.No other statistically significant difference was observed for complications.Conclusions Each type of defunctioning stoma has its advantages and disadvantages.The authors endorse temporary ileostomy over temporary colostomy.However,there is not a strong evidence for the superiority of one temporary stoma over another for colorectal anastomoses.Large scale RCTs and high quality studies are needed.
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ObjectiveTo investigate the impacts of neural stem cells (NSCs) transplantation on spinal pathology and ultrastructure after spinal cord injury (SCI) in rats and probe into the protective role of tacrolimus (FK506) on neural regeneration.MethodsCompressive SCI at T8 was induced in the adult SD rats,which were randomly assigned to the control group,FK506 group,NSCs group and NSCs + FK506 group.The differences of neural regeneration in each group were compared at days 7,14,28 and 56 after injury by motor evoked potentials ( MEP),HE staining,immunohistochemical staining,ultrastructure observation and image analysis of the myelinated fiber. ResultsThe MEP latency in the NSCs + FK506 group was significantly shorter than that in other groups at day 28 ( P ＜ 0.05 ).HE staining revealed that only local necrosis presented in the NSCs + FK506 group at day 56.More BrdU and NF-200 positive cells were detected with immunohistochemical staining in the other three groups as compared with the control group.Moreover,the positive cells in the NSCs + FK506 group also outnumbered the FK506 group and NSCs group.Electron microscope scan showed edema under the membrane of large myelin sheath in the control group,and classic new myelin sheath and neuraxis in the NSCs + FK506 group at day 56.The regeneration of the nerve fiber in the NSCs + FK506 group was better than that of other three groups (P ＜0.01 ).ConclusionAfter NSCs transplantation for SCI rats,the early combination use of FK506 can improve the pathology and ultrastructure of the regenerative nerve fiber and is conducive to nerve regeneration.