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 explore the association between serum γ-aminobutyric acid ( GABA) levels and the risk of developing type 2 diabetes( T2DM) ． Methods : 187 cases of T2DM patients attending the hospital were selected as the T2DM group，and 187 cases of non-T2DM population attending the same period of time were selected as the control group according to age ( ± 3 years) and gender 1 ∶ 1．On-site questionnaires and physical examination were conducted for the study subjects，and serum levels of GABA，Malondialdehyde ( MDA) and activities of superoxide dismutase ( SOD) and Glutathione peroxidase ( GSH-Px) were detected by using ELISA kits．The differences in the levels of GABA and oxidative stress indicators ( SOD，GSH-Px，MDA) between the two groups were compared， and the correlation between GABA and oxidative stress indicators was analyzed by Spearman's method; GABA and oxidative stress indicators were divided into three groups according to their control quartiles，respectively ［low level group ( Q1: ＜P25) ，medium level group ( Q2: P25 －P75) ，high level group ( Q3: ＞P75) ］，and conditional logistic regression was applied to analyze the relationship between GABA，oxidative stress indicators and the risk of develo- ping T2DM; the dose-response relationship between GABA，oxidative stress indicators and the risk of developing T2DM was analyzed by using restricted cubic spline ( RCS) ． Results : T2DM group ( P＜0. 05) ．Spearman's correlation analysis showed that GABA level was positively correlated with SOD and GSH-Px activities and negatively correlated with MDA level ( P＜0. 001) ．Conditional logistic regression analysis showed that medium levels of SOD and GSH-Px as well as medium and high levels of GABA were protective factors for T2DM compared with low levels in each group ( P＜0. 05) ．RCS results showed that a negative dose-response relationship between GABA，GSH-Px and the risk of developing T2DM，and SOD showed a trend of decreasing and then increasing the risk of developing T2DM ( P＜0. 05) ． Conclusion Serum GABA levels have been associated with the risk of developing T2DM．As serum GABA levels increase，the risk of developing T2DM may decrease．

Objective:To develop a training content framework for hospice volunteers based on the competency model.Methods:This was a qualitative study. A draft of the training content framwork for hospice volunteers was first formed according to results of literature review and qualitative interviews based on the competency model. From December 2023 to March 2024, two rounds of Delphi consultation with 16 experts were conducted to develop the final version of the system, and the weights of each indicator were determined with analytic hierarchy process.Results:Among the 14 consulting experts who completed two rounds of consultation, including 10 females, all held intermediate or above professional titles, and their working years ranged from 10 to 34 years, covering fields of hospice care, nursing management, clinical nursing and nursing education. In two rounds of consultation the expert positive coefficient was 14/16 and 14/14, the expert authority coefficient was 0.882 and 0.893, and the Kendall coordination coefficient of all indicators was 0.109 and 0.161 ( P<0.01), the coefficient of variation was 0-0.31 and 0-0.19, respectively. The final version of the system consisted of 3 first-level indicators, 7 second-level indicators, 20 third-level indicators, and 55 specific training contents. The three first-level indicators were knowledge, skill, role and value, and the weight coefficients were 0.335, 0.313 and 0.352, respectively. Each judgment matrix was consistent. Conclusions:A training content system for hospice care volunteers has been developed in this study, which may be used for medical institutions and organizations to train hospice care volunteers.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

OBJECTIVE To promote the application of drones in emergency rescue and related fields， expand “low-altitude+ medical” rescue services， and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones （2025 Edition） （hereinafter referred to as the Consensus） was jointly initiated by the Division of Therapeutic Drug Monitoring， Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit， organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline， resulting in a preliminary draft. Delphi method was employed， and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated， the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose， principles， and applicable scenarios， basic requirements， and operational procedures for low-altitude transport and delivery of emergency medications； distribution requirements and precautions for controlled substances， fragile medications， and temperature-sensitive medications； and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Objective To study the effect of wall thickness on the accuracy(trueness and precision)of 3D printed models.Methods The 3D scanning data of the standard gypsum dental arch model was imported into Exocad software.And four sets of models were de-signed,including horseshoe shaped solid model and horseshoe shaped hollow models with different wall thicknesses(2 mm,3 mm,4 mm).On the first and seventh day after printing,the 3D scanning data of resin models were imported into Geomagic software.Deviation analysis were performed on 3D printed models for the root mean square(root mean square,RMS).Results The trueness range of the four groups of printed models on the first day was(34.63±4.17)μm to(45.26±6.50)μm,there was no statistical difference.The pre-cision range was(30.25±10.18)μm to(47.65±14.77)μm,and the precision of the solid group was lower than the other three groups(P＜0.05).The trueness range of the four groups of printing models on the 7th day was(49.00±9.11)μm to(69.25±9.70)μm.The trueness of the 2 mm wall thickness group was lower than that of the solid group and the 4 mum wall thickness group(P＜0.05).Con-clusion The accuracy of printing models with different wall thicknesses was within the clinical acceptance range.There was no statisti-cally significant difference in the trueness values of the four groups of printing models on the first day.The precision value of the solid group was the lowest.On the 7th day,the trueness of the wall thickness of 2 mm group was lower than that of the solid group and the 4 mum wall thickness group.

Objective:With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade.Methods:The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi′s world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC).Results:From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/10 5, and the crude mortality rate was 714.96/10 5. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. Conclusions:The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.

Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.

AIM:To investigate the expression profile and biological significance of long noncoding RNA(lncRNA)zinc finger antisense 1(ZFAS1)in the brains of mice with diabetic encephalopathy(DE).METHODS:Ten db/m mice served as the normal control group,while twenty 22-week-old db/db mice were used to establish the DE model and randomly divided into two subgroups:ten as the db/db model control and the remaining ten receiving ZFAS1 gene knockdown(db/db+sh-ZFAS1)via lentiviral transfection.Weekly measurements of body weight and blood glucose levels were performed.Brain tissues were collected for Nissl staining to evaluate neuronal damage,TUNEL assay to detect apop-tosis,and immunofluorescence staining to examine neural biomarker expression.Serum levels of tumor necrosis factor-α(TNF-α)and oxidative stress markers,including reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px),were determined.Western blot was conducted to quantify the protein expression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),p38 mitogen-activated protein kinase and phosphorylated p38(p-p38)in brain tissues.The expression levels of ZFAS1 and caspase-3 mRNA were determined by RT-qPCR.RESULTS:Knockdown of ZFAS1 in db/db mice significantly improved cognitive function,alleviated hippocampal neuronal damage,and reduced body weight and blood glucose levels(P<0.01).More-over,oxidative stress was mitigated,as evidenced by decreased MDA and ROS levels(P<0.01)and increased activity of antioxidant enzymes,GSH-Px,SOD and CAT(P<0.01 or P<0.05).Meanwhile,ZFAS1 silencing down-regulated Bax and p-p38/p38 protein expression(P<0.01 or P<0.05)while up-regulating Bcl-2(P<0.01).Consistently,RT-qPCR confirmed significant down-regulation of ZFAS1 and caspase-3 mRNA levels(P<0.01).CONCLUSION:lncRNA ZFAS1 is highly expressed in the hippocampus of DE mice.Down-regulation of ZFAS1 expression enhances cognitive func-tion,suppresses oxidative stress,and inhibits neuronal apoptosis,thereby attenuating neural damage in DE.