Hepatitis B virus (HBV) DNA integration occurs during the reverse transcription process of HBV replication, which develops in the early stages of HBV infection and accompanies the entire disease course. The integration of HBV DNA is detrimental to the attainment of clinical cure goals and also raises the risk of developing liver cancer. Theoretically, nucleos(t)ide analogs can reduce the synthesis of new double-stranded linear DNA, but there is no clearance function for hepatocytes that have already integrated HBV. Therefore, patients with serum HBV DNA-negative conversions still have the risk of developing liver cancer. As an immunomodulatory drug, interferon can not only inhibit viral replication but also inhibit or even eliminate existing clonally amplified hepatocytes carrying integrated HBV DNA fragments. However, there are currently few studies on the effects of nucleos(t)ide analogues and interferon therapy on HBV DNA integration. Thus, large-scale clinical studies are urgently needed for further clarification.

Objective:To explore the implementation of standardized preventive nursing training for venous thromboembolism (VTE) based on the analyze, design, development, implement and evaluation model (ADDIE model), and evaluate the effectiveness of the training.Methods:From September 2021 to December 2022, a special training group was established. The specialized training courses were designed and developed guided by the "National Medical Quality and Safety Improvement Goals", based on the ADDIE model, combined with literature research and Delphi expert consultation. In May 2023, 20 thrombosis liaison nurses from 16 ClassⅢ Grade A hospitals across the country were trained on VTE standardized preventive nursing. After training, the Kirkpatrick evaluation method was used to evaluate the training effectiveness from the aspects of nurse satisfaction with the training, knowledge and skills, implementation of key job technologies, and organizational satisfaction.Results:The satisfaction of thrombosis liaison nurses with the training objectives, content, methods, and teachers of VTE standardized preventive nursing training based on the ADDIE model was all 100%. Compared with before training, there was a statistically significant improvement in the theoretical, operational, and overall scores of thrombosis liaison nurses after training ( P<0.05). In terms of the implementation of key technologies for the position, the execution rate of the thrombosis liaison nurse returning to the unit for retraining other personnel was 90%, with a total of 516 nurses receiving training. After training, the theoretical, operational, and overall scores of the 351 nurses who participated in pre-and post training assessments all improved compared to before training, with statistically significant differences ( P<0.05) . Conclusions:VTE standardized preventive nursing training based on the ADDIE model can effectively improve the comprehensive capacity of nurses in VTE prevention, and nurses have a high recognition of the training program.

For two young female patients with extramedullary recurrence of reproductive system after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. And the characteristics of extramedullary relapse of reproductive system are summarized for exploring possible effective treatments.

Objective:To investigate the clinical effect of CAG stimulating regimen for refractory adult early T cell precursor acute lymphoblastic leukemia (ETP-ALL) complicated with fusarium infection and the clinical features as well as antifungal strategy of cutaneous fusarium infection.Methods:The diagnosis and treatment of 1 adult patient diagnosed as ETP-ALL complicated with cutaneous fusarium infection in the First Hospital of Jilin University in September 2020 were retrospectively analyzed, and related literatures were reviewed.Results:VICP chemotherapy regimen showed no effectiveness in this patient who was presented with persistent agranulocytosis complicated with cutaneous fusariosis infection. After amphotericin B therapy for infection, he achieved the stable disease and successfully underwent CAG stimulating regimen salvage treatment. The minimal residual disease turned into negative after consolidation chemotherapy based on the myeloid regimen. Finally this patient survived from haploid allogeneic hematopoietic stem cell transplantation after consolidation chemotherapy and fusarium was under the control by using posaconazole as secondary prevention therapy.Conclusions:CAG stimulating regimen can be recommended as reinduction therapy for relapsed/refractory ETP-ALL. Sequential therapy of amphotericin B followed by posaconazole can be a useful antifungal strategy for fusarium infection.

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Objective:To evaluate the clinical value of Xing's ureteroileal anastomosis technique in radical cystectomy.Methods:The data of 38 patients who underwent radical cystectomy with Xing's ureteroileal anastomosis technique at Cancer Hospital, Chinese Academy of Medical Sciences and Beijing Chaoyang Hospital from July 2013 to June 2021 were retrospectively reviewed. There were 30 males and 8 females. The mean age was 61.6±15.1 years old. The mean body mass index (BMI) was 25.1±2.7 kg/m 2. The American Society of Anesthesiology (ASA) graded 25 cases as grade 1, 10 cases as grade 2 and 3 cases as grade 3. There were 35 cases with stage cT 2N 0M 0 and 3 cases with cT 3N 0M 0. All patients underwent radical cystectomy and ileal conduit, and the ureteroileal anastomosis was performed using the Xing's ureteroileal anastomosis technique. Afferent loop entry was divided equally into two lumens. After 1.5 cm-long lengthwise incisions, each ureter was directly and end-to-end anastomosed to the aforementioned lumens. Postoperative information was recorded, including ureteric stricture, ureteric reflux, hydronephrosis, anastomotic leakage, renal calculus, urinary tract infection, and pyelonephritis. Results:Ureteroileal anastomosis was performed successfully in 38 cases with 76 units. The median follow-up time was 35.6 (17.0, 46.3) months. Three patients developed unilateral anastomotic stenosis after operation. Five patients had unilateral ureteral reflux. Two patients had unilateral hydronephrosis. No anastomotic leakage, urinary tract infection, or pyelonephritis occurred after the operation. Renal calculus appeared in 3 cases, all on the left unit.Conclusions:Xing's ureteroileal anastomosis technique is a simple method with few postoperative and good functional outcomes.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To explore the incidence rates, clinical features, risk factors and its impacts on survival of central nervous system complications (CNSC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:From June 2011 to October 2018, 237 consecutive patients undergoing allo-HSCT were retrospectively analyzed.Results:The incidence of CNSC was 10.5%(25/237) and the median time 82(-4 - 810) days post-transplantation. The most common instances of CNSC were drug-associated encephalopathy (n=6), CNS infection (n=5), unexplained convulsions (n=4), metabolic encephalopathy (n=3), immune-related encephalopathy (n=3), primary central relapse (n=3) and cerebrovasculopathy (n=1). The most common clinical symptom was epileptic seizure (n=11). CsA-related encephalopathy was manifested mainly as posterior reversible encephalopathy syndrome on brain MRI. Metabolic encephalopathy is mostly demyelination. Most hippocampal lesions were caused by immune-related encephalopathy or CNS infection. Analysis of risk factors indicated that umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation were high risk factors for post-transplantation occurrence of CNSC. Survival analysis suggested that non-relapse mortality rate (42.9%, 9/21) in group with CNSC of malignant hemoblastosis was higher than that in group without CNSC (15.3%, 27/176) and inter-group difference was statistically significant ( χ2=9.511, P=0.005). The 1/3-year OS rates in group with CNSC were lower than those in group without CNSC (56.6% vs 77.8%; 37.1% vs 65.7%). And the difference was statistically significant ( P=0.022). Conclusions:With a complex etiology, CNSC is one of serious complications after allo-HSCT and it significantly reduces the overall survival rate of patients. Umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation are high-risk groups for CNSC.

Objective:To explore immune cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)by using mathematical function models.Methods:From June 2011 to May 2015, 65 patients with malignant hematological disorders were retrospectively analyzed. Immune cell frequencies and absolute counts were detected at day 14/28/42 and month 2/3/6/9/12/18/24 post-allo-HSCT. The immune cells included CD3 + T, CD4 + helper T, CD8 + effector T, regulatory T, CD19 + B, CD3 -CD56 + NK and CD3 + CD56 + NKT. Kinetic curve models and mathematical equations were established by utilizing curve model estimation. Results:Cubic curve models were observed for the changes of immune cell frequencies. Except for CD3 + T, CD8 + T and NK cells, the changes of absolute counts of immune cells conformed to cubic curve models. The reconstructed kinetic models of CD8 + T and NK cells after allo-HSCT were associated with relapse. Conclusions:Immune cell reconstitution after allo-HSCT conforms to certain mathematical function curve models. It may provide a new strategy for in-depth studies of immune reconstitution after allo-HSCT.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.