OBJECTIVE To analyze the risk factors associated with serum digoxin concentration （SDC） exceeding the warning threshold and to construct a risk prediction model. METHODS Clinical data were retrospectively collected from hospitalized patients who received regular oral digoxin and completed therapeutic drug monitoring at Guangzhou First People’s Hospital and Nansha Branch of Guangzhou First People’s Hospital between September 2020 and March 2025. Patients with SDC＞2.0 ng/mL were classified as exceeding the warning threshold group， while those with SDC≤2.0 ng/mL were classified as the non-exceeding the warning threshold group. Based on univariate factor analysis， multivariate Logistic regression analysis was used to identify independent risk factors for SDC exceeding the warning threshold. A prediction model was developed and a nomogram was plotted accordingly. The discriminative ability of the model was evaluated by receiver operating characteristic （ROC） curve analysis， and the calibration curve were plotted to assess the calibration of the model. The Hosmer-Lemeshow test was employed to evaluate the goodness of fit of the model， and clinical utility was evaluated by decision curve analysis （DCA）. RESULTS A total of 254 patients were included， among whom 49 patients （19.29%） had SDC exceeding the warning threshold. Univariate factor analysis and multivariate Logistic regression analysis showed that increased daily dose per kilogram of body weight， advanced age， concomitant coronary heart disease， elevated serum creatinine levels， concomitant use of amiodarone， and concomitant use of deslanoside wer e independent risk factors for SDC exceeding the warning threshold （ P ＜0.05）. The area under the ROC curve of the model was 0.869 （95% confidence interval： 0.818-0.920）， with a sensitivity of 0.796 and a specificity of 0.842. The Hosmer-Lemeshow test showed good calibration （ P ＝0.570）. The calibration curve was closely aligned with the ideal curve， with a mean absolute error of 0.012. The model provided a higher net benefit across a threshold probability range of 6% to 82%. CONCLUSIONS The increased daily dose per kilogram of body weight， advanced age， concomitant coronary heart disease， elevated serum creatinine levels， concomitant use of amiodarone， and concomitant use of deslanoside are independent risk factors for SDC exceeding the warning threshold. The nomogram prediction model developed based on the aforementioned factors can be used to predict the risk of SDC exceeding the warning threshold.

BACKGROUND: At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS: Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS: Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001). CONCLUSIONS It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.
Humans ; Male ; Prostatectomy/methods* ; Prostatic Neoplasms/diagnosis* ; Middle Aged ; Aged ; Positron Emission Tomography Computed Tomography/methods* ; Biopsy ; Multiparametric Magnetic Resonance Imaging ; Prostate-Specific Antigen/metabolism*

Objective:To explore the clinical features, genetic traits and prognosis status of acute myeloid leukemia (AML) patients with TP53 mutation.Methods:A retrospective case series study was performed. Clinical data of 42 AML patients with TP53 mutation abundance of at least 10% who were admitted to the First Hospital of Jilin University from April 2018 to August 2023 were collected. Chromosomal karyotypes were detected using fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) was performed on bone marrow samples from these patients. The Kaplan-Meier method was utilized to analyze the recurrence-free survival (RFS) of 22 patients who achieved complete remission (CR) after induction therapy, as well as the overall survival (OS) of 39 patients who underwent treatment. The Cox proportional hazards model was employed to analyze the factors influencing RFS and OS. Thirty-one patients who underwent induction therapy for ≥ 2 courses were divided into the non-refractory group (22 cases) and the refractory group (9 cases) based on whether CR was achieved after induction therapy, and the clinical and genetic characteristics and prognosis of the two groups were compared.Results:Among the 42 AML patients with TP53 mutation, there were 26 males and 16 females, with a median age [ M( Q1, Q3)] of 57.0 (44.0, 63.5) years. At the initial stage, the median white blood cell count in peripheral blood was 4.06×10 9/L (2.59×10 9/L, 27.36×10 9/L), the median proportion of bone marrow primitive cells was 45.25% (29.00%, 80.63%), the proportion of primitive and immature cells in bone marrow cell immune analysis was 28.70% (12.71%, 61.48%), and the median TP53 mutation abundance was 55.48% (38.72%, 73.31%). Among the 42 patients, 23 cases (54.76%) had complex chromosomal karyotypes, with the most frequent abnormal chromosomes being chromosome 5 (47.62%, 20 cases), chromosome 7 (45.24%, 19 cases) and chromosome 17 (26.19%, 10 cases). The mutant genes with high mutation frequency were DNMT3A (19.05%, 8 cases), N/KRAS (19.05%, 8 cases), ASXL1 (16.67%, 7 cases) and NPM1 (16.67%, 7 cases). Among the 39 patients with detailed TP53 mutation data, 36 had missense mutations and 3 had frameshift mutations. In the non-refractory and refractory groups, the N/KRAS mutation rates were 13.6% (3/22) and 55.6% (5/9), respectively ( P = 0.027). The median RFS time of 22 CR patients after induction therapy was 109 d (95% CI: 57-483 d). The results of multivariate Cox regression analysis showed that complex chromosomal karyotype was an independent risk factor for RFS ( HR = 11.819, 95% CI: 1.345-103.880, P = 0.028). The median RFS time of patients without and with complex chromosomal karyotypes was 842 d (95% CI: 0-1 716 d) and 148 d (95% CI: 88-208 d), respectively, and the difference in RFS between the two groups was statistically significant ( P = 0.001). The median OS time of 39 patients receiving treatment was 151 d (95% CI: 75-227 d). The results of multivariate Cox regression analysis showed that NPM1 gene mutation was an independent protective factor for OS ( HR = 0.289, 95% CI: 0.075-1.114, P = 0.071). The median OS time of patients with and without NPM1 gene mutation was 1 562 d (95% CI: 610- 1 710 d) and 136 d (95% CI: 99-173 d), respectively, and the difference in OS between the two groups was statistically significant ( P = 0.020). Conclusions:TP53-mutant AML patients often have poor chromosomal karyotypes and genetic abnormalities, while refractory AML patients often have N/KRAS mutation. The complex chromosomal karyotype is a risk factor for RFS, while NPM1 gene mutation is a protective factor for OS.

Objective To investigate the status of occult hepatitis B virus infection(OBI)among blood donors in Quzhou,Zhejiang,and to analyze the mutation of S region in blood donors with anti-HBc+alone and non anti-HBc+alone.Methods The OBI samples were screened by ELISA and NAT;the HBV DNA was amplified and sequenced;20 anti-HBc+alone and 25 not anti-HBc+alone samples were obtained.Results The detection rate of OBI in Quzhou was 0.10%(155/161 045),and the positive rate of anti-HBc was 74.19%(115/155).The detection rate of OBI increased with the age of blood donors(P＜0.05),but was not related to gender.The positive rate of anti-HBc+alone was 22.58%(35/155),and that of not anti-HBc alone was 51.61%(80/155).Among the 45 OBI sequencing samples,the proportion of B and C geno-type was73.33%(33/45)and 20.00%(9/45),respectively.The mutation sites of blood donors in the anti-HBc+alone group were more than those in the not anti-HBc+alone group,and the mutation rates of S114T and V168A on MHR were significantly different(P＜0.05).Conclusion The genotype of OBI infection in Quzhou is mainly type B.The mutation sites of blood donors with anti-HBc+alone are higher than those with not anti-HBc+alone,which may be more suitable as one of the OBI screening indicators.

Hepatitis B vaccination is the most economical and effective way to prevent HBV infection.The advances in molecular biology and genetic engineering have continuously improved the manufacturing process of vaccines,and hepatitis B vaccine has gradually developed from the initial plasma-derived vaccine to the currently used recombinant vaccine.Preventive hepatitis B vaccine has been clinically tested in patients with HBsAg seroclearance to increase the level of anti-HBs,with certain safety and efficacy.As one of the multiple targets for new drugs in the treatment of chronic hepatitis B,a therapeutic hepatitis B vaccine based on HBsAg is already in the stages of research and development and clinical trial.

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.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Background/Aims: To investigate the autoantibody against fumarate hydratase (FH), which is a specific liver failure-associated antigen (LFAA) and determine whether it can be used as a biomarker to evaluate the prognosis of acute-on-chronic liver failure (ACLF). Methods: An immunoproteomic approach was applied to screen specific LFAAs related to differential prognosis of ACLF (n=60). Enzyme-linked immunosorbent assay (ELISA) technology was employed for the validation of the frequency and titer of autoantibodies against FH in ACLF patients with different prognoses (n=82). Moreover, we clarified the expression of autoantibodies against FH in patients with chronic hepatitis B (n=60) and hepatitis B virus-related liver cirrhosis (n=60). The dynamic changes in the titers of autoantibodies against FH were analyzed by sample collection at multiple time points during the clinical course of eight ACLF patients with different prognoses. Results: Ultimately, 15 LFAAs were screened and identified by the immunoproteomic approach.Based on ELISA-based verification, anti-FH/Fumarate hydratase protein autoantibody was chosen to verify its expression in ACLF patients. ACLF patients had a much higher anti-FH autoantibody frequency (76.8%) than patients with liver cirrhosis (10%, p=0.000), patients with chronic hepatitis B (6.7%, p=0.022), and normal humans (0%, p=0.000). More importantly, the frequency and titer of anti-FH protein autoantibodies in the serum of ACLF patients with a good prognosis were much higher than that of patients with a poor prognosis (83.9% vs 61.5%, p=0.019; 1.41±0.85 vs 0.94±0.56, p=0.017, respectively). The titer of anti-FH autoantibodies showed dynamic changes in the clinical course of ACLF. Conclusions The anti-FH autoantibody in serum may be a potential biomarker for predicting the prognosis of ACLF.

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.

ObjectiveTo develop basic training courses for family doctor teams for people with disabilities. MethodsUtilizing the methods and theories of the World Health Organization (WHO) rehabilitation competency framework (RCF), and referring to the WHO universal health coverage global competency framework, the rehabilitation competency characteristics of family doctor teams for people with disabilities in community settings were analyzed, and a basic training course system for these teams based on the RCF was developed. Results and ConclusionBased on RCF, a competency framework for family doctor teams serving people with disabilities has been constructed. The objectives, content and training course system for basic rehabilitation training has been established.