OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

Two new coumarin glycosides were isolated and purified from the dichloromethane fraction of Angelica biserrata 75% ethanol extract using silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Through the comprehensive use of modern spectroscopic methods, their structures were identified as angelmanetin A (1) and angelmanetin B (2), respectively.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Aim To investigate the im-munomodulatory effects of Ononin on Th17/Treg bal-ance and inflammatory responses,and to evaluate its neuroinmune regulatory role in ischemic stroke.Methods A Foxp3 promoter-driven luciferase reporter assay was used to assess the effect of Ononin on Foxp3 transcriptional activity.The effect of Ononin on the dif-ferentiation of na?ve CD4+T cells into Th 17 and Treg subsets was evaluated by flow cytometry.A transient middle cerebral artery occlusion(tMCAO)model was established in mice to evaluate the effects of Ononin on infarct size,neurological recovery,body weight resto-ration,and survival rate.Flow cytometry and RT-PCR were conducted to elucidate the immunological mechanisms underlying Ononin's effects.Results On-onin significantly enhanced Foxp3 promoter activity,promoted the differentiation of na?ve CD4+T cells into Treg cells,and suppressed Th17 polarization.In the tMCAO model,Ononin significantly reduced acute in-farct size,improved survival,ameliorated long-term neurological deficits,and increased Treg cell propor-tions in ischemic brain tissue.Conclusions Ononin modulates peripheral and central inflammation by resto-ring the Th17/Treg immune balance,thereby exerting significant immunomodulatory effects.Its therapeutic benefit in ischemic stroke is closely linked to immune balance restoration.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

The construction method and simulation parameter settings for the discrete element model of Jianwei Xiaoshi Granules, as the primary material of Jianwei Xiaoshi Tablets, are not yet clear. The accuracy of the simulation model significantly influences the dynamic response characteristics between granules. Therefore, it is necessary to calibrate the parameters to improve the accuracy of the simulation parameters. Using the repose angle of Jianwei Xiaoshi Granules as the response value, the response surface methodology was employed to optimize and calibrate the discrete element parameters. Physical experiments were conducted to determine the physical properties of Jianwei Xiaoshi Granules. Based on the Hertz-Mindlin with Johnson-Kendall-Roberts(JKR) V2 model and virtual simulation methods, a repose angle determination model was constructed in EDEM software. The repose angle was measured using image analysis and numerical fitting methods. The Plackett-Burman experiment was used to screen the initial parameters for significance in the discrete element simulation. The significant parameters were then subjected to a steepest ascent experiment to determine the optimal parameter range. Furthermore, based on the Box-Behnken experiment, a second-order regression equation between significant parameters and repose angle was established, with the repose angle of 37.64° in the physical experiment as the target value. The regression equation was optimized and solved. The significance screening experiment revealed that the granule-granule static friction coefficient, granule-granule rolling friction, and granule-steel plate rolling friction of Jianwei Xiaoshi Granules significantly influenced the simulated repose angle. The optimal parameter combination was found to be 0.330, 0.222, and 0.229. The simulation results with this optimal parameter combination showed that there was no significant difference between the simulated repose angle and the repose angle obtained in the physical experiment, with a relative error of 0.05%, which further validated the reliability of the calibrated discrete element parameters for Jianwei Xiaoshi Granules.
Drugs, Chinese Herbal/chemistry* ; Calibration ; Computer Simulation

Identification of critical material attributes(CMAs) is a key issue in the quality control of large-scale TCM products like Jianwei Xiaoshi Tablets. This study focuses on the granules of Jianwei Xiaoshi Tablets, using tablet tensile strength as the primary quality attribute. A method for identifying the CMAs and a design space for the granules were established, along with a predictive model for the granule CMAs based on Fourier transform near-infrared spectroscopy(FT-NIR). First, granules of Jianwei Xiaoshi Tablets with different properties were prepared using a partial factorial design method from the design of experiments(DOE). The powder properties of the granules were measured. An orthogonal partial least squares(OPLS) model was established to correlate the powder properties with tensile strength. Based on the characteristics of the comprehensive variables extracted by OPLS, the independent variables with the greatest explanatory power for tensile strength were identified. FT-NIR technology was then employed to establish a predictive model for the granule CMAs. The final CMAs identified were hygroscopicity, moisture content, D_(50), collapse angle, mass flow rate, and tapped density. The coefficients of determination of the prediction set(R■) and relative percentage deviation(RPD) of the prediction set for flowability, D_(50), and moisture content were 0.891, 0.994, and 0.998; and 2.97, 12.4, and 20.7, respectively. The established OPLS model clearly identified the impact of various factors on tensile strength, demonstrating good fit results. The model exhibited high prediction accuracy and can be used for the rapid and accurate determination of CMAs in granules of Jianwei Xiaoshi Tablets.
Drugs, Chinese Herbal/chemistry* ; Tablets/chemistry* ; Tensile Strength ; Quality Control ; Spectroscopy, Fourier Transform Infrared ; Spectroscopy, Near-Infrared

Objective:To analyze awareness, willingness, the status of using, and related factors of HIV pre-exposure prophylaxis (PrEP) in men who have sex with men (MSM) in Shaanxi Province to provide a reference for the next step of HIV prevention and control strategy.Methods:Using a cross-sectional study design from March to May 2022, with the assistance of MSM social organizations in Xi'an, relying on the network platform and MSM Social organizations, a convenient sampling method was used to recruit MSM with an estimated sample size of 900. The inclusion criteria were male aged ≥18, having had same-sex sexual intercourse in the last twelve months, HIV-negative or unknown status of infection. An electronic questionnaire was made with the help of questionnaire-star and an anonymous self-administered questionnaire was used to collect information on socio-demographic characteristics, sexual behavior, awareness and using of PrEP, etc. A logistic regression model was used to analyze related factors of PrEP awareness and use in MSM. SPSS 25.0 software was used for statistical analysis. Results:Among 981 MSM subjects, 76.55% (751/981) had heard of PrEP, and 42.51% (417/981) were aware of PrEP. Among those who knew about PrEP, 74.34% (310/417) had homosexual sexual activity in the last six months, 99.03% (307/310) were willing to use PrEP, and 40.97% (127/310) were using PrEP. The multivariate logistic regression analysis model results showed that nationality (other ethnic groups:a OR=4.48,95% CI:1.28-15.68),education level (high school or technical secondary school: a OR=3.01,95% CI:1.49-6.07; universities or colleges: a OR=2.86,95% CI:1.47-5.57; master degree: a OR=5.10,95% CI:2.37-10.98), monthly income 5 000-10 000 yuan (a OR=1.70,95% CI: 1.00-2.88), tested for HIV in the past 12 months (a OR=1.87,95% CI:1.34-2.61) were related factors of PrEP knowledge awareness. Singlehood (a OR=0.46,95% CI:0.26-0.81) and consulted professionals about PrEP (a OR=9.56,95% CI:4.58-19.96) were related factors of PrEP use. Conclusions:The proportion of willingness to use PrEP was higher among MSM in Shaanxi Province, but the awareness rate and utilization rate of MSM for PrEP were low. The cognition of PrEP should be further improved to promote the correct use of PrEP among MSM.