Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

PURPOSE: To compare the effects of empirical and modified hemostatic resuscitation for liver blast injury combined with seawater immersion. METHODS: Thirty rabbits were subjected to liver blast injury combined with seawater immersion, and were then divided into 3 groups randomly (n = 10 each): group A (no treatment after immersion), group B (empirical resuscitation with 20 mL hydroxyethyl starch, 50 mg tranexamic acid, 25 IU prothrombin complex concentrate and 50 mg/kg body weight fibrinogen concentrate), and group C (modified resuscitation with additional 10 IU prothrombin complex concentrate and 20 mg/kg body weight fibrinogen concentrate based on group B). Blood samples were gathered at specified moments for assessment of thromboelastography, routine coagulation test, and biochemistry. Mean arterial pressure, heart rate, and survival rate were also documented at each time point. The Kolmogorov-Smirnov test was used to examine the normality of data distribution. Multigroup comparisons were conducted with one-way ANOVA. RESULTS: Liver blast injury combined with seawater immersion resulted in severe coagulo-fibrinolytic derangement as indicated by prolonged prothrombin time (s) (11.53 ± 0.98 vs. 7.61 ± 0.28, p＜0.001), activated partial thromboplastin time (APTT) (s) (33.48 ± 6.66 vs. 18.23 ± 0.89, p＜0.001), reaction time (R) (min) (5.85 ± 0.96 vs. 2.47 ± 0.53, p＜0.001), decreased maximum amplitude (MA) (mm) (53.20 ± 5.99 vs. 74.92 ± 5.76, p＜0.001) and fibrinogen concentration (g/L) (1.19 ± 0.29 vs. 1.89 ± 0.32, p = 0.003), and increased D-dimer concentration (mg/L) (0.38 ± 0.32 vs. 0.05 ± 0.03, p = 0.005). Both empirical and modified hemostatic resuscitation could improve the coagulo-fibrinolytic states and organ function, as indicated by shortened APTT and R values, decreased D-dimer concentration, increased fibrinogen concentration and MA values, lower concentration of blood urea nitrogen and creatine kinase-MB in group B and group C rabbits in comparison to that observed in group A. Further analysis found that the R values (min) (4.67 ± 0.84 vs. 3.66 ± 0.98, p = 0.038), APTT (s) (23.16 ± 2.75 vs. 18.94 ± 1.05, p = 0.001), MA (mm) (60.10 ± 4.74 vs. 70.21 ± 3.01, p < 0.001), and fibrinogen concentration (g/L) (1.68 ± 0.21 vs. 1.94 ± 0.16, p = 0.013) were remarkably improved in group C than in group B at 2 h and 4 h after injury. In addition, the concentration of blood urea nitrogen (mmol/L) (24.11 ± 1.96 vs. 21.00 ± 3.78, p = 0.047) and creatine kinase-MB (U/L) (85.50 ± 13.60 vs. 69.74 ± 8.56, p = 0.013) were lower in group C than in group B at 6 h after injury. The survival rates in group B and group C were significantly higher than those in group A at 4 h and 6 h after injury (p < 0.001), however, there were no statistical differences in survival rates between group B and group C at each time point. CONCLUSIONS Modified hemostatic resuscitation could improve the coagulation parameters and organ function better than empirical hemostatic resuscitation.
Animals ; Rabbits ; Resuscitation/methods* ; Liver/injuries* ; Seawater ; Blast Injuries/therapy* ; Fibrinogen/administration & dosage* ; Male ; Tranexamic Acid/administration & dosage* ; Immersion ; Hydroxyethyl Starch Derivatives/administration & dosage*

PURPOSE: To construct a decision-making app for pre-hospital damage control resuscitation (PHDCR) for severely injured patients, and to make a preliminary trial test on the effectiveness and usability aspects of the constructed app. METHODS: Decision-making algorithms were first established by a thorough literature review, and were then used to be learned by computer with 3 kinds of text segmentation algorithms, i.e., dictionary-based segmentation, machine learning algorithms based on labeling, and deep learning algorithms based on understanding. B/S architecture mode and Spring Boot were used as a framework to construct the app. A total of 16 Grade-5 medical students were recruited to test the effectiveness and usability aspects of the app by using an animal model-based test on simulated PHDCR. Twelve adult Bama miniature pigs were subjected to penetrating abdominal injuries and were randomly assigned to the 16 students, who were randomly divided into 2 groups (n = 8 each): group A (decided on PHDCR by themselves) and group B (decided on PHDCR with the aid of the app). The students were asked to complete the PHDCR within 1 h, and then blood samples were taken and thromboelastography, routine coagulation test, blood cell count, and blood gas analysis were examined. The lab examination results along with the value of mean arterial pressure were used to compare the resuscitation effects between the 2 groups. Furthermore, a 4-statement-based post-test survey on a 5-point Likert scale was performed in group B students to test the usability aspects of the constructed app. RESULTS: With the above 3 kinds of text segmentation algorithm, B/S architecture mode, and Spring Boot as the development framework, the decision-making app for PHDCR was successfully constructed. The time to decide PHDCR was (28.8 ± 3.41) sec in group B, much shorter than that in group A (87.5 ± 8.53) sec (p < 0.001). The outcomes of animals treated by group B students were much better than that by group A students as indicated by higher mean arterial pressure, oxygen saturation and fibrinogen concentration and maximum amplitude, and lower R values in group B than those in group A. The post-test survey revealed that group B students gave a mean score of no less than 4 for all 4 statements. CONCLUSION A decision-making app for PHDCR was constructed in the present study and the preliminary trial test revealed that it could help to improve the resuscitation effect in animal models of penetrating abdominal injury.
Animals ; Swine ; Resuscitation/methods* ; Mobile Applications ; Humans ; Algorithms ; Emergency Medical Services/methods* ; Male ; Decision Making ; Female

Objective:To investigate the incidence of venous thromboembolic disease (VTE) in urological inpatients during perioperation.Methods:The clinical data of 7 988 inpatients admitted to the Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2019 were analyzed retrospectively. The cohort included 5 657 males and 2 331 females. The average age of the enrolled patients was (56.3±15.8) years old, and the body mass index was (23.8±3.2) kg/m 2. There were 1 628 malignant tumors patients and 6 360 non-malignant tumors patients in the cohort. Of all the patients, 7 725 cases received surgical treatment. All patients were scored with the Caprini Risk Assessment Model (2005) after admission and 1 655 cases were classified as very low risk, 2 940 cases were low risk, 2 922 cases were medium risk, 345 cases were high risk and 126 cases were very high risk. Patients with Caprini score ≥ 2 and/or clinical symptoms were examined by venous color Doppler ultrasound. CT pulmonary angiography was performed for patients with chest pain, chest tightness, decreased blood oxygen saturation and other symptoms suspected of pulmonary embolism according to clinical judgment to screen the incidence of VTE. Results:Among the 7 988 cases, 180 cases (2.25%, 180/7 988) with VTE were found by preoperative examination, including 1 case (0.01%, 1/7 988) with pulmonary embolism. There were 199 new cases with VTE after operation, and the incidence of new VTE after operation was 2.58% (199/7 725). Among them, pulmonary embolism was found in 7 cases, with a incidence of 0.09% (7/7 725). Only 7.92% (30/379) of the VTE patients had VTE-related symptoms. The operations with higher incidence of VTE were radical cystectomy, nephroureterectomy, radical prostatectomy and radical nephrectomy, with the incidence of 11.61% (13/112), 10.87 (10/92), 8.25% (16/194) and 6.16% (22/357) respectively.Conclusions:The incidence of VTE in hospitalized patients with urinary surgery in this study is much higher than previously reported. Most of the patients with VTE are asymptomatic. The operations with high incidence of VTE after operation are radical cystectomy, nephroureterectomy, radical prostatectomy and radical nephrectomy. Therefore, it is necessary to carry out VTE screening for hospitalized patients in urology department, which is helpful to realize early intervention of VTE and reduce the risk of VTE progression and pulmonary embolism.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

Objective:The aim of this study is to investigate the relationship between fat mass and obesity associated ( FTO) gene polymorphism and the risk of gestational diabetes mellitus (GDM), and provide clues and basis for the study of GDM mechanism. Methods:The case group of GDM pregnant women who delivered at the First Affiliated Hospital of Shanxi Medical University from March 1, 2012 to July 30, 2014 were selected, and matched the control group among non-GDM pregnant women by age, gestational age and residential address, and 324 cases and 318 controls were finally included. DNA was extracted and genotyped, and min P test and unconditional logistic regression model were used to estimate the relationship between FTO gene polymorphism and GDM. Results:At gene level, we did not find the association between FTO and the risk of GDM ( P>0.05). After adjusted for family history of diabetes, pre-pregnancy body mass index and multiple comparisons using false discovery rate method, unconditional logistic regression analysis showed that pregnant women who carried the rs11075995 TT genotype ( OR=0.59, 95 %CI: 0.35-0.89), rs3826169 GG genotype ( OR=0.59, 95 %CI: 0.35-0.88), and rs74245270 GA genotype ( OR=0.69, 95 %CI: 0.49-0.98), GA or AA genotype( OR=0.70, 95 %CI: 0.50-0.97) had reduced risk of GDM. However, pregnant women who carried the rs74018601 GA genotype ( OR=1.51, 95 %CI: 1.07-2.12), GA or AA genotype ( OR=1.46, 95 %CI: 1.06-2.02), rs7205009 AA genotype ( OR=1.83, 95 %CI: 1.18-2.86), GA or AA genotype ( OR=1.53, 95 %CI: 1.08-2.19), and rs9888758 AG genotype ( OR=1.43, 95 %CI: 1.02-2.00) had elevated risk of GDM. Conclusion:The polymorphisms of FTO gene rs11075995,rs3826169, rs74245270, rs74018601, rs7205009 and rs9888758 were associated with the risk of GDM.

Objective:To investigate the relationship between folic acid supplementation and the risk of preeclampsia (PE).Methods:A total of 9 048 pregnant women were selected from the First Hospital of Shanxi Medical University in Taiyuan from March 2012 to September 2016. Among them, 882 pregnant women with PE were divided into case group, and 8 166 pregnant women without PE were divided into control group. Information on demographic characteristics, folic acid supplementation, maternal complications, and other factors were collected by face-to-face interviews after child birth in the hospital. Unconditional logistic regression analyses were used to investigate the relationship between folic acid supplementation and the risk of PE and the effects of pre-pregnancy BMI on the relationship of folic acid supplementation with the risk of PE.Results:Compared with nonusers, folic acid supplement users had reduced risk of PE ( OR=0.79, 95 %CI: 0.64-0.96). Folic acid supplementation before and during pregnancy were negatively related with the risk of PE ( OR=0.63, 95 %CI: 0.49-0.81). Pregnant women who used folic acid tablets only or used both folic acid tablets and multivitamin containing folic acid had reduced risk of PE ( OR=0.81, 95 %CI: 0.66-0.99; OR=0.64, 95 %CI: 0.49-0.85). No significant relationship was observed in the multivitamin group. Supplemental folic acid doses of <400, 400, and >400 μg/d were related with reduced risk of PE ( OR=0.62, 95 %CI: 0.42-0.91; OR=0.81, 95 %CI: 0.66-0.99; OR=0.68, 95 %CI: 0.49-0.94). After stratified by pre-pregnancy BMI, pregnant women who used folic acid supplementation, those with pre-pregnancy BMI<24.0 kg/m 2 had reduced risk of PE ( OR=0.75, 95 %CI: 0.59-0.96). However, no significant relationship was observed in women with pre-pregnancy BMI≥24.0 kg/m 2. Conclusions:Folic acid supplementation before and during pregnancy were related with reduced risk of PE. Pre-pregnancy BMI might affect the relationship between folic acid supplementation and the risk of PE. Appropriate folic acid supplementation should be recommend for women with different pre-pregnancy BMI.

Objective: To investigate the relations between dietary intake during pregnancy and the incidence of their babies with small for gestational age (SGA). Methods: Data on demographics, dietary intake of protein, fat, and carbohydrates of the pregnant mothers during the first, second and third trimester, were collected. Information related to birth weight and gestational age of the infants were also gathered. A total of 8 102 women, who delivered their babies at the First Affiliated Hospital of Shanxi Medical University from March 2012 to September 2016, were enrolled in this project. Among them, 961 mothers had infants with SGA but the other 7 141 of them having normal infants. Unconditional logistic regression model was used to analyze the effect of dietary nutrient intake on SGA the first, second and third trimester. Results: We found that low dietary intake of protein during the first trimester and following trimesters during pregnancy were positively associated with higher risk of SGA (OR=1.534, 95%CI: 1.217-1.934; OR=1.268, 95%CI: 1.005-1.599; OR=1.310, 95%CI: 1.036-1.655). When adjusting for maternal pre-pregnancy BMI, we found that when mothers were with a pre-pregnancy BMI less than 18.5 or with low maternal intake of protein during the first trimester, positive association with higher risk of SGA (OR=1.872, 95%CI: 1.033-3.395; OR=1.754, 95%CI: 1.125-2.734), was noticed. However, for mothers with a pre-pregnancy BMI between 18.5 and 24.0 or with low protein intake during the first trimester, significant association with higher risk of SGA (OR=1.465, 95%CI: 1.089-1.972) was found. Conclusions Through our observation, maternal dietary intake during pregnancy seemed to be associated with the risk of SGA but the effects of dietary intake were different, according to the BMI of pre-pregnancy population. Early pregnancy appeares as the key period for dietary intake which may influence the SGA.

Objective To analyze the influencing factors of vaginal birth after cesarean (VBAC) in re-pregnancy puerperae and mother-infant outcomes.Methods A total of 290 re-pregnant women after cesarean were enrolled in the study,and 210 pregnant women were successfully given vaginal delivery,among whom 180 cases with vaginal birth were selected as the observation group,and 80 cases with cesarean section were as control group.The factors affecting the success of vaginal delivery after cesarean section were analyzed,and the maternal and neonatal outcomes between the two groups were compared.Results The univariate analysis showed that fetal head position,fetal abdominal circumference,fetal biparietal diameter,uterine height,premature rupture of membranes,Bishop score,and epidural anesthesia of two groups were statistically significant(P ＜ 0.05);Multivariate logistic regression analysis showed that Bishop score,fetal abdominal circumference,fetal head position,and epidural anesthesia were independent influencing factors of VBAC success (P ＜ 0.05).The incidence rates of uterine rupture,the rate of neonatal asphyxia,hospitalization rate,Apgar score of two groups showed no significant difference (P ＞ 0.05).The bleeding rates at 2,24 h in the observation group were lower than that in the control group (P ＜ 0.05).Conclusion There are various factors that affect the success of vaginal delivery after cesarean section,and prenatal examination should be scientifically evaluated.If there is no indication of cesarean section,maternal vaginal delivery should be guided to improve the maternal and child outcomes and life quality of mother and child.

Objective To analyze the influencing factors of vaginal birth after cesarean (VBAC) in re-pregnancy puerperae and mother-infant outcomes.Methods A total of 290 re-pregnant women after cesarean were enrolled in the study,and 210 pregnant women were successfully given vaginal delivery,among whom 180 cases with vaginal birth were selected as the observation group,and 80 cases with cesarean section were as control group.The factors affecting the success of vaginal delivery after cesarean section were analyzed,and the maternal and neonatal outcomes between the two groups were compared.Results The univariate analysis showed that fetal head position,fetal abdominal circumference,fetal biparietal diameter,uterine height,premature rupture of membranes,Bishop score,and epidural anesthesia of two groups were statistically significant(P ＜ 0.05);Multivariate logistic regression analysis showed that Bishop score,fetal abdominal circumference,fetal head position,and epidural anesthesia were independent influencing factors of VBAC success (P ＜ 0.05).The incidence rates of uterine rupture,the rate of neonatal asphyxia,hospitalization rate,Apgar score of two groups showed no significant difference (P ＞ 0.05).The bleeding rates at 2,24 h in the observation group were lower than that in the control group (P ＜ 0.05).Conclusion There are various factors that affect the success of vaginal delivery after cesarean section,and prenatal examination should be scientifically evaluated.If there is no indication of cesarean section,maternal vaginal delivery should be guided to improve the maternal and child outcomes and life quality of mother and child.