BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies

AIM:To investigate the effects of Shaoyao-Gancao decoction(SGD)on inflammation and mucosal barrier damage in rats with 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced inflammatory bowel disease(IBD).METHODS:Forty-eight male SD rats were randomly divided into normal group,model group,high-dose(500 mg/kg),medium-dose(250 mg/kg)and low-dose(125 mg/kg)SGD groups,and balsalazide sodium(1 g/kg)group.All rats were pre-administered for 3 d,and on the 4th day of the experiment,they were fasted for 24 h.Except for the normal group,the rats in the other 5 groups were given enema mixed with TNBS(100 mg/kg)and 50％ethanol,and continued to be adminis-tered for 5 d after modeling.After modeling,the disease activity index(DAI)was evaluated.After the experiment,the levels of nitric oxide(NO)and myeloperoxidase(MPO)in serum and colonic tissues of rats were determined.RT-qPCR and Western blot were used to determine tumor necrosis factor-α(TNF-α),cyclooxygenase-2(COX-2),inducible nitric oxide synthase(iNOS)and nuclear factor-κB(NF-κB)in the colon of rats.The expression of tight junction proteins zonu-la occludens-1(ZO-1)and claudin 2 in rat colon tissues was determined by immunofluorescence staining.RESULTS:Compared with normal group,the weight of rats in model group was decreased,the colon was shortened,DAI and colon tissue macroscopic scores were significantly increased(P<0.05),colon pathological injury was serious,and NO and MPO levels in serum and colon tissues of the rats in model group were significantly increased(P<0.05).The mRNA and pro-tein expression levels of TNF-α,COX-2,iNOS and NF-κB in colon tissues were significantly increased(P<0.01),while the expression levels of ZO-1 and claudin 2 were significantly decreased(P<0.01).Compared with model group,the body weight and colon shortening of rats in SGD groups were alleviated,DAI and macroscopic scores of colon tissues were significantly decreased(P<0.05),the pathological damage of colon was improved,and the levels of NO and MPO in se-rum and colon tissues of rats were significantly decreased(P<0.05).The mRNA and protein expression levels of TNF-α,COX-2,iNOS and NF-κB in colon tissues were significantly decreased(P<0.05),while the expression levels of ZO-1 and claudin 2 were significantly increased(P<0.05).CONCLUSION:Treatment with SGD effectively attenuates the inflam-matory response and intestinal mucosal barrier damage caused by TNBS-induced IBD in rats.

Objective:To investigate the effects of conventional anesthesia combined with low dose esketamine on pain and stress response in patients undergoing laparoscopic total hysterectomy.Methods:A total of 150 patients with laparoscopic total hysterectomy admitted to our hospital from Jan. 2022 to Dec. 2023 were selected as subjects. All patients were divided into control group and study group by coin toss method, with 75 cases in each group. The control group were given conventional anesthesia, and the study group were given a small dose of esketamine. Intraoperative sedation, hemodynamics at different times, postoperative pain, stress response and the incidence of adverse reactions were compared between the two groups.Results:There was no significant difference in hemodynamics between the two groups ( P>0.05). Mean arterial pressure (MAP) was (94.84±6.02), (86.14±5.99) mmHg, systolic blood pressure (SBP) was (96.48±5.72), (96.48±5.69) mmHg; Heart rate (HR) was 95.51±5.95, 84.05±5.57 times/min, while they were 102.05±6.13, 93.71±6.25, 105.03±6.07, 104.37±6.02 mmHg, 102.49±6.87, 90.51±5.86 times/min, respectively in the control group. The study group was significantly lower than the control group ( P<0.05). SpO2 at extubation and extravasation were (97.47±1.24) % and (98.11± 1.24) % in study group and (96.32±1.21) % and (97.03±1.23) % in the control group, significantly higher than those in the control group ( P<0.05). VAS scores at 3 h, 6 h, 12 h and 24 h were 1.71±0.35, 2.58±0.53, 3.27±0.68, 3.86±0.82 in the study group and 2.13±0.42, 3.74±0.75, 4.52±1.01, 4.53±1.04 in the control group. The study group was significantly lower than the control group ( P<0.05). Study group 5-hydroxytryptamine (5-HT), substance P (SP), norepinephrine, NE) levels were 29.53±7.68, 37.44±8.16, 49.71±9.56 ng/mL, and 52.81±10.04, 54.62±10.25, 61.23±10.08 ng/mL in the control group, significantly lower than those in the control group ( P<0.05). Postoperative 2 d study group calcitonin gene related peptide (calcitonin gene related peptide, CGRP), neuropeptide Y (NPY) and cortisol (Cor) levels were 158.41±27.06 pg/mL, 127.84±24.21 pg/mL and 240.37±31.55 nmol/L. The control group was 175.49±30.28 pg/mL, 153.92±28.63 pg/mL, 251.18±34.92 nmol/L, and the study group was significantly lower than the control group ( P<0.05). The incidence of adverse reactions in the study group was 10.67% (8/75), and the control group was 16.00% (12/75), with no statistical significance ( P>0.05) . Conclusion:Conventional anesthesia combined with low-dose esketamine can help reduce intraoperative hemodynamic changes in patients with laparoscopic total hysterectomy, improve sedation effect, relieve postoperative pain, reduce postoperative pain factors and oxidative stress related indexes of patients without increasing adverse reactions, and has good efficacy and safety.

Objective:To translate the Nurse Delirium Care Competency Scale (NDCCS) into Chinese and test the validity and reliability of Chinese version of NDCCS among ICU nurses.Methods:According to Brislin translation model, the Chinese version of NDCCS was developed by forward translation, back translation, cross-cultural adaptation and pre-survey. From October to December of 2023, 338 ICU nurses from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were selected by cross-sectional survey to test the reliability and validity of Chinese version of NDCCS.Results:A total of 329 valid questionnaires were collected. There were 50 males and 279 females, aged 20-53 years old. The Chinese version of NDCCS included 6 dimensions and 27 items. The scale-level content validity value was 0.985, and the item-level content validity value was 0.800-1.000. Exploratory factor analysis showed a six-factor structure, the cumulative variance contribution rate was 75.700%, the Cronbach′s α coefficients of the scale amount table were 0.952, and the Cronbach′s α coefficients of the dimensions were 0.811- 0.936,and the retest reliability was 0.932.Conclusions:The Chinese version of the NDCCS has good reliability and validity, and it is suitable for assessing the delirium care competence of ICU nurses in China.

Nursing information security is an essential component of providing high-quality nursing services and is an important guarantee for the construction of large-scale health care data application systems. This article reviewed the concept, assessment tools, and influencing factors of nursing information security, aiming to provide references for hospital nursing managers to effectively assess information security and improve nurses′ information literacy.

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, belonging to the type II CRISPR/Cas system, is an effective gene-editing tool widely used in different organisms, but the size of Streptococcus pyogenes Cas9 (SpCas9) is quite large (4.3 kb), which is not convenient for vector delivery. In this study, we used a codon-optimized Staphylococcus aureus Cas9 (SaCas9) system to edit the tyrosinase (tyr), oculocutaneous albinism II (oca2), and paired box 6.1 (pax6.1) genes in the fish model medaka(Oryzias latipes), in which the size of SaCas9 (3.3 kb) is much smaller and the necessary protospacer-adjacent motif (PAM) sequence is 5'-NNGRRT-3'. We also used a transfer RNA (tRNA)‍-single-guide RNA (sgRNA) system to express the functional sgRNA by transcription eitherin vivo or in vitro, and the combination of SaCas9 and tRNA-sgRNA was used to edit the tyr gene in the medaka genome. The SaCas9/sgRNA and SaCas9/tRNA-sgRNA systems were shown to edit the medaka genome effectively, while the PAM sequence is an essential part for the efficiency of editing. Besides, tRNA can improve the flexibility of the system by enabling the sgRNA to be controlled by a common promoter such as cytomegalovirus. Moreover, the all-in-one cassette cytomegalovirus (CMV)‍-SaCas9-tRNA-sgRNA-tRNA is functional in medaka gene editing. Taken together, the codon-optimized SaCas9 system provides an alternative and smaller tool to edit the medaka genome and potentially other fish genomes.
Animals ; Oryzias/genetics* ; Gene Editing/methods* ; CRISPR-Cas Systems ; Codon ; RNA, Guide, CRISPR-Cas Systems/genetics* ; Monophenol Monooxygenase/genetics* ; CRISPR-Associated Protein 9/genetics* ; RNA, Transfer/genetics* ; Staphylococcus aureus/genetics* ; PAX6 Transcription Factor/genetics*

ObjectiveTo investigate the mechanism of Renshen Guben oral liquids（RGOL） in treatment of mice with renal fibrosis based on metabolomics and network pharmacology. MethodC57BL/6 mice were randomly divided into control group， model group and RGOL group， 12 mice in each group. Except for the control group， mice in the other groups were induced into unilateral ureteral obstruction（UUO） model by UUO. After preparation of the model， an aqueous solution of 4.2 g·kg^-1 extract powder was administered by gavage to RGOL group for 14 d， and an equal amount of distilled water was administered by gavage to the control and model groups. After the last administration on the 14^th day， urine was collected and detected by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QQQ-MS/MS） with 0.1% formic acid aqueous solution as mobile phase A， and acetonitrile-isopropanol（70∶30） as mobile phase B for gradient elution（0-1 min， 5%B； 1-5 min， 5%-30%B； 5-9 min， 30%-50%B； 9-11 min， 50%-78%B； 11-13.5 min， 78%-95%B； 13.5-14 min， 95%-100%B； 14-16 min， 100%B； 16-16.1 min， 100%-5%B； 16.1-18 min， 5%B）， column temperature of 40 ℃， flow rate of 0.4 mL·min^-1， electrospray ionization（ESI）， collection range of m/z 50-900. Through network pharmacology， the targets of components in RGOL and the targets of renal fibrosis were analyzed interactively， and the key components and key targets were screened by network topology analysis， and DAVID platform was used to predict the signaling pathways of RGOL for the treatment of renal fibrosis. ResultA total of 7 differential metabolites involving 8 metabolic pathways were identified in RGOL for the treatment of renal fibrosis. The network pharmacology revealed that 36 key components in RGOL were related to 7 differential metabolites， mainly ginsenosides， notoginsenosides and nucleotides. Based on the herbs-components-targets-pathways network， a total of 23 key targets related to the treatment of renal fibrosis by RGOL were highlighted， which together with the differential metabolites were involved in linoleic acid metabolism， arginine biosynthesis， tricarboxylic acid cycle（TCA）， arginine and proline metabolism and other pathways. ConclusionBased on metabolomics and network pharmacology， this study preliminarily identified 7 differential metabolites， 36 potential pharmacodynamic components and 23 key targets and 4 key pathways in RGOL for the treatment of renal fibrosis， providing an experimental basis for the clinical application and mechanism study of this preparation.

【Objective】 To investigate the independent risk factors of urinary tract infection (UTI) in recipients under-going renal transplantation of donation after brain death (DBD), so as to provide a theoretical basis for the prevention and control of postoperative UTI. 【Methods】 A retrospective study was conducted for recipients who received renal transplantation of DBD in our hospital during Jan.2021 and Dec.2021. The recipients were divided into the infection group (n=26) and non-infection group (n=74) according to the incidence of UTI 3 months after operation. The risk factors of UTI were identified with univariate and multivariate analyses. 【Results】 The incidence of UTI was 26%. Univariate analysis showed that gender, postoperative urinary fistula, time of indwelling catheter and time of indwelling double J tube were the influencing factors of UTI (P<0.05). Forward stepwise regression analysis showed time of indwelling double J tube (OR=1.086,95%CI:1.003-1.177,P=0.042) and time of indwelling catheter(OR=4.687,95%CI:2.064-10.645, P<0.010) were the independent risk factors of UTI (P<0.05). 【Conclusion】 The time of indwelling catheter and time of indwelling double J tube are the independent factors of UTI after renal transplantation of DBD.

Objective:To investigate the relationship between serum free triiodothyronine (FT 3) and the severity and prognosis of elderly patients with coronavirus disease 2019 (COVID-19). Methods:Clinical data of the elderly patients aged≥65 years old with COVID-19 who were admitted to the Ninth People′s Hospital of Wuxi from December 27, 2022 to January 18, 2023 were collected. The laboratory examinations of the non-severe and the severe/critical groups were compared. Patients were divided into group T1 (FT 3<2.51 pmol/L), group T2 (FT 3=2.51 to 2.95 pmol/L, ), and group T3 (FT 3>2.95 pmol/L) according to the FT 3 level. Independent sample t test was used for comparison between groups. Logistic regression analysis was performed to evaluate the risk factors for severe/critical disease, and to analyze the risk of severe/critical COVID-19 in elderly patients with different FT 3 levels. The receiver operator characteristic (ROC) curve was drawn to analyze the predictive value of FT 3 on the occurrence of severe/critical disease in patients. Kaplan-Meier survival curve and log-rank test were used to analyze the 30-day survival rate of elderly COVID-19 patients. Results:Among the 190 patients, the FT 3 level in the severe/critical group was (2.54±0.30) pmol/L, which was significantly lower than that in the non-severe group ((2.91±0.69) pmol/L), and the difference was statistically significant ( t=-3.42, P=0.001). Elevated serum FT 3 level was a protective factor for severe/critical disease in elderly COVID-19 patients (odds ratio ( OR)=0.139, 95% confidence interval ( CI) 0.034 to 0.577, P=0.007). There were 66 patients in the T1 group, 61 in the T2 group and 63 in the T3 group, respectively. After adjusted for sex, age, history of lung diseases, history of cardiac diseases, history of hypertension, history of diabetes mellitus, history of cerebral infarction, white blood cell count, lactate dehydrogenase, D-dimer, free thyroxine and thyrotropin, the risk of developing severe/critical disease in group T1 and group T2 were 10.982 folds and 3.695 folds of that in group T3, respectively (both P<0.05). The area under ROC curve of FT 3 of predicting severe/critical COVID-19 in the elderly patients was 0.731. The sensitivity and specificity were 0.733 and 0.659, respectively. The cut-off value was 2.53 pmol/L. The 30-day survival rate in patients with FT 3<2.53 pmol/L was significantly lower than that in patients with FT 3≥2.53 pmol/L ( χ2=13.49, P<0.001). Conclusions:The elevated level of FT 3 is a protective factor for progression to severe/critical disease in elderly patients with COVID-19. The evaluation of serum FT 3 could predict the severity and prognosis of elderly COVID-19 patients.