Objective:To investigate the decay law of 177Lu-DOTA-TATE in the treatment of neuroendocrine tumors in patients with external radiation and the radiation dose to the surrounding persons. Methods:The radiation dose rate from patients to the surrounding environment after 177Lu-DOTA-TATE treatment was measured using a handheld radiation dosimeter at different times. The decay law of the radiation dose rate with time and distance was analyzed, and the radiation levels at different distances from the patients and the radiation dose of the patients to the surrounding persons were estimated. Results:The external radiation dose rate from the patients decayed exponentially with time rapidly in the early stage and gradually slowly in the later stage. The effective half-life was (1.41±0.25) h (0.9-1.8)h in the rapid decay stage and (40.18±6.0) h (32.7-54.73 h) in the slower decay stage. At 0 h after injection, the normalized mean radiation dose rates at 0.25, 0.5, 1, 2, and 3 m away from the patient were 41.7±6.3, 20.0±3.0, 7.2±3.8, 3.4±0.9, and 1.9±0.4 μSv·h -1·GBq -1, respectively. The radiation doses to doctors, nurses, physicists, and positioning technicians were 2.0, 10.24, 1.08, and 4.05 μSv/patient, respectively. Conclusions:The external radiation dose rate from patients receiving 177Lu-DOTA-TATE treatment rapidly decreases over time and distance. The radiation levels that patients may cause to the surrounding workers are within the allowable range of national standards. After discharge, patients should reduce close and long-term contact with the surrounding persons.

Objective:To estimate the renal absorbed dose in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE and to assess the radiation safety and guide the treatment. Methods:The dosimetric calculations of patients treated with 177Lu-DOTA-TATE were carried out based on planar images of single photon emission computed tomography (SPECT). The regions of interest (ROIs) of the whole body and kidneys were delineated and converted into activity. Accordingly, the time-activity curves of the ROIs were obtained. The effective half-lives and cumulative activity of ROIs were calculated through the fitting of a single exponential equation of the ROIs. Then the absorbed doses were calculated based on the medical internal radiation dosimetry (MIRD) formalism. Results:A total of 11 patients with neuroendocrine tumors received 18 cycles of treatments with 177Lu-DOTA-TATE. The effective half-lives of 177Lu-DOTA-TATE in the whole body and kidneys were 20.0-99.8 h and 38.2-75.2 h, respectively, with an average of (57.3 ± 21.4) h and (53.1 ± 12.5) h, respectively. The renal absorbed doses of 177Lu-DTA-TATE were 0.25-1.48 mGy/MBq, with an average of (0.90 ± 0.31) mGy/MBq. The minimum and maximum renal absorbed doses in a single treatment cycle were 1.8 Gy and 9.6 Gy, respectively, while the maximum renal absorbed dose in multiple treatment cycles was 21.7 Gy. Conclusions:The renal absorbed doses in the treatment of neuroendocrine tumors using 177Lu-DOTA-TATE were estimated. The result indicate that the renal absorbed doses were lower than the tolerable dose limits. This study is expected to guide the precise treatment of neuroendocrine tumors.

Objective: To observe the effects of general anesthesia and intravertebral anesthesia on the patients' temperature, perfusion index(PI) and coagulation function. Methods: From January 2016 to December 2017, 60 patients in the First Hospital of Jiaxing undergoing elective line of great saphenous varicose veins surgery were selected.According to the random number table, the patients were divided into the general anesthesia group(group G, n=30) and intraspinal anesthesia group(group I, n=30). The general condition, operation time, the core temperature(tympanic membrane temperature) before anesthesia(T0), 10 min after anesthesia(T1), 20 min later(T2), 30 min later(T3), and the PI with no-infusion upper limb were recorded.The changes of coagulation function before anesthesia(T0) and after surgery(T4) were observed by extraction of the thrombus(TEG). Results: The core body temperature of T1, T2 and T3 was significantly decreased in both two groups(F_G=58.789, P=0.000, F_I=2.965, P=0.035), and the hypothermia of group G was greater than that of group I(t₁=-2.998, t₂=-5.985, t₃=-7.705; P<0.05). The PI of T1, T2 and T3 was significantly higher than T0 in both two groups(F_G=5.439, P=0.002, F_I=3.404 P=0.020), and the increase of group G was greater than that of group I(t₁=2.065, t₂=2.041, t₃=2.649; P<0.05). In group G, TEG examination was significantly prolonged(F=5.482, P=0.023), and no significant changes were observed in group I. Conclusion The hypothermia of the patients and the increase of PI increased significantly, and the R time index of TEG is prolonged, and the anesthesia in the spinal canal has no obvious effect on the coagulation function.

Objective: To analyze many indicators during perioperative period of liver transplantation in patients with end-stage liver disease, only to seek related factors that can accurately predict short-term(≤three months)outcome. Methods: We analyzed retrospectively clinical data of consecutive patients with end-stage liver diseases undergone liver transplantation in a single treatment center. Logistic regression analysis was used to analyze the perioperative indicators including recipient gender, age, body mass index, preoperative serum albumin level, serum sodium concentration, urea nitrogen level and donor-recipient blood group, et al. Correlated factors were analyzed by the method of multivariate logistic regression. Statistical processing package was SAS 9.1.3 soft. The difference was statistically significant with P<0.05. Results: 18/165 patients died within 3 months after transplantation(mortality rate: 10.9 %). According to the result of univariate analysis, the indicators correlated with early mortality which were statistically significant were preoperative serum sodium, blood urea nitrogen, PT-INR, CTP score, MELD score and MELD-Na score. On the base of the result of Logistic multiple regression. However, only MELD-Na score was associated with 3 months prognosis(P=0.001, β=-2.510, OR=0.088, 95 % CI=0.037~0.349). Conclusions Preoperative MELD-Na score is an independent risk factor for short-term survival in patients with end-stage liver disease. Higher MELD-Na score is, the early mortality is higher.

OBJECTIVE To explore and evaluate the value of CT in diagnosis of malignant tumor of maxillary sinus and the accuracy of the involved bone wall by comparing the preoperative CT imaging with the pathologic examination.METHODS 11 patients without maxillary sinus squamous cell carcinoma and lymph node metastasis received pathological examination and enhanced CT scan before operation,partial or total maxillary resection were implemented according to the CT features and scope.The position and azimuth of the cut bone tissue samples were marked.The specimens were routinely fixed,decalcified,embedded,sliced and HE stained to observe the bone tissue pathological changes on the bone wall under light microscope.RESULTS Nasal sinus enhancement CT scan showed that the medial wall of maxillary sinus were all resorped and invaded(4 cases lack inner wall).Anterior wall was invaded in 6 cases,superior wall in 7 cases and bottom wall in 3 cases,posterior and exterior wall in 9 cases;After ruling out the cases without internal wall of maxillary sinus,the inner wall of the maxillary sinus was invaded by cancer cells,so was the front wall and the bottom wall.Those showed bone wall erosion on preoperative CT with continuous change but without interruption and accompanied by bone wall thickening and hardening were found without tumor invasion by postoperative pathological verification.CONCLUSION Bone wall damage on preoperative CT does not mean tumor invasion,and the probability of each maxillary sinus wall invasion is different;the comprehensive analysis found that for wormhole like change of bone wallon preoperative CT with continuous bone wall thickening and hardening of the 'reconstruction of bone destruction',there was no tumor invasion by postoperative pathological validation;Routine selection analysis of bone tissue pathology can supplement the extent diagnosis of malignant tumor of maxillary sinus on preoperative CT scan,so it can accurately estimate the T staging of tumor.It may provide a more effective basis for selection of minimally invasive surgery,postoperative evaluation of surgical effect and formulating more comprehensive treatment protocol.

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
APOBEC-1 Deaminase ; genetics ; metabolism ; Base Sequence ; Blastomeres ; cytology ; metabolism ; CRISPR-Cas Systems ; Embryo, Mammalian ; metabolism ; pathology ; Female ; Fibroblasts ; metabolism ; pathology ; Gene Editing ; methods ; Gene Expression ; HEK293 Cells ; Heterozygote ; Homozygote ; Humans ; Point Mutation ; Primary Cell Culture ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; beta-Globins ; genetics ; metabolism ; beta-Thalassemia ; genetics ; metabolism ; pathology ; therapy

This study was aimed to optimize the extraction technology of Shu-Feng Ding-Chuan(SFDC) granules in the Huang-Qin(HQ)group by Box-Behnken response surface methodology(RSM).With three major characteristic components (baicalin,praeruptorin A and solid content in extraction liquid),the effects of four factors,such as the concentration of ethanol,the dosage of ethanol,the duration of extraction and the extraction times,were investigated by the single factor experiment.Then,the range of parameters of key factors was further studied and explored by Box-Behnken RSM.The results of single factor experiment and Box-Behnken design showed that the optimum preparation conditionswere 8-fold 70% ethanol,extracted for 2 times,with 1.0 h per each time.Under these conditions,the transfer rates of baicalin and praeruptor in A were 89.57% and 87.90%,respectively.And the transfer rateof solid content was 32.35%.It was concluded that the single factor experiment combined with RSM can be used in theoptimization of extraction technology for SFDC granules in the HQ group.This technique wasstable and feasible,which provided scientific evidences for the industrial production.

OBJECTIVETo investigate the preoperative risk factors of portal venous thrombosis (PVT) after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension.

METHODSClinical data was collected for 127 patients who underwent splenectomy and gastric pericardial devascularization for portal hypertension at our hospital between January 2010 and December 2012.The patient data were analyzed retrospectively according to patient status of presence or absence of PVT postoperatively.The preoperative risk factors of PVT were statistically analyzed.

RESULTSThere were no significant differences between the postoperative PVT-positive and-negative groups in regards to sex, age, receipt of emergency surgery, presence of ascites, admission to hospital for upper gastrointestinal bleeding, grade of esophageal-gastric varices, Child-Pugh classification, spleen vein diameter, liver function (as determined by levels of alanine aminotransferase, total bilirubin, direct bilirubin, albumin, globulin, cholinesterase, and gamma-glutamyltransferase), renal function (as determined by creatinine level), and coagulation function (as determined by prothrombin time, prothrombin activity degree, activated partial thromboplastin time, international normalized ratio, fibrinogen, thrombin time, and antithrombin III).However, there were significant differences between the groups for the parameters of postoperative PVT presence, upper gastric bleeding history, aspartate aminotransferase level, and blood urea nitrogen level (all P less than 0.05).Portal vein diameter and history of upper gastric bleeding were both identified as independent risk factors for PVT (P less than 0.05).Incidence of postoperative PVT was higher in patients who had portal vein diameter > 13.15 mm (cutoff value of 13.75 mm) and in patients who had a history of upper gastric bleeding.

CONCLUSIONPortal vein diameter and history of upper gastric bleeding were independent risk factors for PVT occurrence after splenectomy and gastric pericardial devascularization in patients with liver cirrhosis and portal hypertension.

Antithrombin III ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage ; Humans ; Hypertension, Portal ; surgery ; Incidence ; Liver Cirrhosis ; Portal Vein ; Retrospective Studies ; Risk Factors ; Splenectomy ; Stomach ; blood supply ; surgery ; Venous Thrombosis ; epidemiology ; etiology ; gamma-Glutamyltransferase

Objective To evaluate the predictive effect of preoperative CTP score,MELD score and MELD-Na score on short-term prognosis (≤ 3 months) after liver transplantation,to analyze factors which correlated with survival,and to seek indicators that accurately predicted short-term outcomes.Methods The clinical data of 73 consecutive patients with end-stage liver diseases who underwent liver transplantation in a single center were retrospectively analyzed.The area under the ROC curve (AUC) was used to determine the predictive power.Correlated factors were analyzed by multivariate logistic regression.The statistical processing package used was SAS 9.1.3 software.Results 11 (15.1％) of 73 patients died within 3 months after liver transplantation.The areas under the ROC curve of the preoperative CTP score,MELD score and MELD-Na score for predicting short-term survival were 0.817,0.839 and 0.860 respectively.There was no significant difference among these 3 scoring systems.On univariate analysis,indicators significantly correlated with early mortality were preoperative serum sodium,serum urea,PT-INR,CTP score,MELD score and MELD-Na score.On logistic multiple regression,only MELD-Na score remained as a significant indicator (P =0.001,β =-2.496,OR =0.085,95％ CI:0.019 ～ 0.370).Conclusions The MELD-Na scoring system showed superior predictability of early mortality in patients who underwent liver transplantation.The preoperative MELD-Na score was an independent risk factor of short-term survival.The higher the MELD-Na score,the higher was the early mortality.