1.Identification of Novel Proteins for Creutzfeldt-Jakob Disease by Integrating Genome-wide Association Data and Human Brain Proteomes
Wan-Ting ZHONG ; Yi-Tong YUAN ; Min ZHANG ; Ruo-Chen DU ; Ling-Yu ZHANG ; Chun-Fang WANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):1040-1047,中插1-中插26
Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate<0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.
2.Clinical Characteristics of Adult Acute Myeloid Leukemia Patients with NUP98::HOXA9 Fusion Gene.
Hai-Xia CAO ; Ya-Min WU ; Shu-Juan WANG ; Zhi-Dan CHEN ; Jing-Han HU ; Xiao-Qian GENG ; Fang WANG ; Ling SUN ; Zhong-Xing JIANG ; Zhi-Lei BIAN
Journal of Experimental Hematology 2025;33(5):1241-1247
OBJECTIVE:
To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene.
METHODS:
From May 2017 to October 2023, among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed.
RESULTS:
Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively.
CONCLUSION
The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans
;
Adult
;
Leukemia, Myeloid, Acute/genetics*
;
Middle Aged
;
Prognosis
;
Nuclear Pore Complex Proteins/genetics*
;
Oncogene Proteins, Fusion/genetics*
;
Mutation
;
Male
;
Female
;
Young Adult
;
Homeodomain Proteins/genetics*
3.Canagliflozin ameliorates ferritinophagy in HFpEF rats.
Sai MA ; Qing-Juan ZUO ; Li-Li HE ; Guo-Rui ZHANG ; Ting-Ting ZHANG ; Zhong-Li WANG ; Jian-Long ZHAI ; Yi-Fang GUO
Journal of Geriatric Cardiology 2025;22(1):178-189
BACKGROUND:
Recent studies have shown that sodium-glucose cotransporters-2 (SGLT2) inhibitors significantly improve major adverse cardiovascular events in heart failure with preserved ejection fraction (HFpEF) patients, but the exact mechanism is unknown. Ferritinophagy is a special form of selective autophagy that participates in ferroptosis. In this study, we aimed to investigate whether ferritinophagy was activated during the occurrence of HFpEF, and whether canagliflozin (CANA) could inhibite ferritinophagy.
METHODS:
We reared Dahl salt-sensitive (DSS) rats on a high-salt diet to construct a hypertensive HFpEF model, and simultaneously administered CANA intervention. Then we detected indicators related to ferritinophagy.
RESULTS:
The expression of nuclear receptor coactivator 4 (NCOA4), as well as microtubule-associated proteins light chain 3 (LC3), Bcl-2 interacting protein 1 (Beclin-1) and p62, were upregulated in HFpEF rats, accompanied by the downregulation of ferritin heavy chain 1 (FTH1), upregulation of mitochondrial iron transporter sideroflexin1 (SFXN1) and increased reactive oxygen species (ROS) production. Above changes were diminished by CANA.
CONCLUSION
Ferritinophagy is activated in HFpEF rats and then inhibited by CANA, leading to HFpEF benefits. The inhibition of ferritinophagy could provide new prospective targets for the prevention and treatment of HFpEF, and provide new ideas for investigating the mechanism of cardiovascular benefit of SGLT2 inhibitors.
4.Mechanisms and Efficacy of Chinese Herbal Medicines in Benign Prostatic Hyperplasia.
Fu WANG ; Dong-Yue MA ; Jiu-Tian YANG ; Dong-Fang LYU ; Qing-He GAO ; Chun-Lei LI ; Chong-Fu ZHONG
Chinese journal of integrative medicine 2025;31(1):73-82
Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men, the incidence of which gradually increases with age and leads to lower urinary tract symptoms (LUTS), which seriously affects the quality of life of patients. Chinese herbal medicines (CHMs) are widely used for the treatment of BPH in China and some other countries. To explore the molecular mechanisms of CHMs for BPH, we conducted a review based on peer-reviewed English-language publications in PubMed and Web of Science databases from inception to December 31, 2023. This article primarily reviewed 32 papers on the use of CHMs and its active compounds in the treatment of BPH, covering animal and cell experiments, and identified relevant mechanisms of action. The results suggest that the mechanisms of action of CHMs in treating BPH may involve the regulation of sex hormones, downregulation of cell growth factors, anti-inflammatory and antioxidative effects, inhibition of cell proliferation, and promotion of apoptosis. CHMs also exhibit α-blocker-like effects, with the potential to relax urethral smooth muscle and alleviate LUTS. Additionally, we also reviewed 4 clinical trials and meta-analyses of CHMs for the treatment of BPH patients, which provided initial evidence of the safety and effectiveness of CHMs treatment. CHMs treatment for BPH shows advantages as a multi-component, multi-target, and multi-pathway therapy, which can mitigate the severity of the disease, improve LUTS, and may become a reliable treatment option in the future.
Prostatic Hyperplasia/drug therapy*
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Humans
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Drugs, Chinese Herbal/pharmacology*
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Male
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Animals
5.Sub-committee of Anesthesiology of Guangzhou Integrated Traditional Chinese and Western Medicine Society.
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
OBJECTIVES:
To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and.
RESULTS:
Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.
CONCLUSIONS
The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans
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Medicine, Chinese Traditional
;
Cancer Pain/therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Drug Delivery Systems
;
Pain Management/methods*
;
China
6.Longitudinal Associations between Vitamin D Status and Systemic Inflammation Markers among Early Adolescents.
Ting TANG ; Xin Hui WANG ; Xue WEN ; Min LI ; Meng Yuan YUAN ; Yong Han LI ; Xiao Qin ZHONG ; Fang Biao TAO ; Pu Yu SU ; Xi Hua YU ; Geng Fu WANG
Biomedical and Environmental Sciences 2025;38(1):94-99
7.Associations of Genetic Risk and Physical Activity with Incident Chronic Obstructive Pulmonary Disease: A Large Prospective Cohort Study.
Jin YANG ; Xiao Lin WANG ; Wen Fang ZHONG ; Jian GAO ; Huan CHEN ; Pei Liang CHEN ; Qing Mei HUANG ; Yi Xin ZHANG ; Fang Fei YOU ; Chuan LI ; Wei Qi SONG ; Dong SHEN ; Jiao Jiao REN ; Dan LIU ; Zhi Hao LI ; Chen MAO
Biomedical and Environmental Sciences 2025;38(10):1194-1204
OBJECTIVE:
To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease.
METHODS:
This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used.
RESULTS:
During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity.
CONCLUSION
Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans
;
Pulmonary Disease, Chronic Obstructive/epidemiology*
;
Exercise
;
Male
;
Female
;
Middle Aged
;
Prospective Studies
;
Aged
;
Genetic Predisposition to Disease
;
Risk Factors
;
United Kingdom/epidemiology*
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Incidence
;
Adult
8.Effectiveness of a shared decision-making intervention with nurses as "decision coaches" in the perioperative period for bladder cancer patients
Jing GUO ; Xinli WANG ; Xiaoxia FANG ; Zhong JING ; Shengjie REN
Chinese Journal of Modern Nursing 2025;31(10):1346-1351
Objective:To explore the effectiveness of shared decision-making intervention with nurses as "decision coaches" in perioperative decision management of bladder cancer patients.Methods:From March 2023 to February 2024, 152 bladder cancer patients in the Department of Urology Surgery of Xinxiang Central Hospital for surgical treatment were selected by convenience sampling. The patients were divided into control group and observation group of 76 cases each using the randomized numerical table method. Control group implemented conventional bladder cancer surgical decision management, and observation group implemented a shared decision-making intervention with nurses as "decision coaches" on this basis, and the intervention period was one week before surgery. Decisional Conflict Scale (DCS), Preparation Decision Making (PrepDM), Patients Satisfaction with Participation in Medical Decision-making Scale, and Decision Regret Scale (DRS) scores were compared between the two groups of patients before and after intervention.Results:Finally 74 patients in control group and 75 patients in observation group completed the study. After the intervention, the DCS scores of observation group were lower than those of control group and before the intervention, and the differences were statistically significant (all P<0.05). After the intervention, the PrepDM scores of observation group were higher than those of control group and before the intervention, and the differences were statistically significant (all P<0.05). One week after surgery, observation group had higher decision-making participation satisfaction scores and lower DRS scores than control group, and the differences were statistically significant (all P<0.05) . Conclusions:Preoperative shared decision-making interventions with nurses as "decision coaches" in bladder cancer patients can effectively reduce preoperative decision conflicts, increase preoperative decision readiness and participation satisfaction with decision-making, and decrease patients' postoperative decision regret.
9.Effects of chronic kidney disease on growth,development and cognitive function of offspring rats,and role of esaxerenone
Chang XU ; Jieqi NIU ; Shuchen ZHANG ; Hongshuang WANG ; Fang FANG ; Yan ZHONG ; Xiangting WANG ; Zheng WANG
Chinese Journal of Pathophysiology 2025;41(2):261-267
AIM:This study aims to investigate the impact of chronic kidney disease(CKD)on the growth,development,and cognitive function of offspring rats,and to evaluate the effects of esaxerenone(ESAX)intervention.METHODS:Thirty female non-pregnant Wistar rats were randomly assigned to three groups:sham operation+pregnancy(control group),UUO+pregnancy(model group),and UUO+pregnancy+esaxerenone(treatment group),with 10 rats in each group.CKD was induced in the UUO+pregnancy and UUO+pregnancy+esaxerenone groups by performing uni-lateral ureteral obstruction(UUO),while the sham operation+pregnancy group underwent a non-ligated and non-clipped ureter procedure.Rats in the treatment group received esaxerenone at a dosage of 1 mg·kg-1·d-1.Vaginal smears were per-formed weekly from the 8th week post-UUO to monitor the estrous cycle.Female and male rats in pre-estrus or estrus were paired in a 2∶1 ratio,and the day with the first appearance of sperm in vaginal smears was recorded as the first day of preg-nancy.Offspring were delivered 21 to 22 days post-gestation,and 10 offspring from each group were selected for further experimentation:sham-offspring(sham-offspr)group,UUO-offspro group,and esaxerenone treatment offspring(ESAX-offspr)group.At 21 days of age,offspring weight and tail length were measured.Behavioral tests,including the open field test,Y maze test,and Morris water maze test,assessed learning and memory abilities.Serum levels of aldosterone,5-hydroxytryptamine(5-HT),and brain-derived neurotrophic factor(BDNF)were measured using ELISA.Serum creati-nine(SCr)and blood urea nitrogen(BUN)levels were assessed using conventional biochemical methods.Renal pathology was examined using Hematoxylin-Eosin(HE)staining.RESULTS:Offspring in the UUO-offspr group had reduced body weight and tail length compared to the sham-offspr group(P<0.05).Behavioral tests indicated that exploration and memo-ry abilities were significantly impaired in the UUO-offspr group compared to the sham-offspr group(P<0.05),while the ESAX-offspr group showed improved behavioral development compared to the UUO-offspr group(P<0.05).ELISA results revealed decreased levels of serum 5-HT,BDNF,and aldosterone in the UUO-offspr group compared to the sham-offspr group(P<0.01),with increased levels in the ESAX-offspr group(P<0.05).Renal function tests showed elevated SCr and BUN levels in the UUO-offspr group compared to the sham-offspr group(P<0.01),while levels in the ESAX-offspr group were reduced(P<0.01).HE staining demonstrated mild tubular dilation and inflammatory cell infiltration in the UUO-offspr group,whereas the ESAX-offspr group had well-arranged tubules with reduced inflammation.CONCLU-SION:Chronic kidney disease adversely affects the growth,development,and cognitive function of offspring rats by 21 days of age.Esaxerenone intervention can mitigate these detrimental effects on growth,development,and cognitive abili-ties in offspring rats.
10.Potential utility of albumin-bilirubin and body mass index-based logistic model to predict survival outcome in non-small cell lung cancer with liver metastasis treated with immune checkpoint inhibitors.
Lianxi SONG ; Qinqin XU ; Ting ZHONG ; Wenhuan GUO ; Shaoding LIN ; Wenjuan JIANG ; Zhan WANG ; Li DENG ; Zhe HUANG ; Haoyue QIN ; Huan YAN ; Xing ZHANG ; Fan TONG ; Ruiguang ZHANG ; Zhaoyi LIU ; Lin ZHANG ; Xiaorong DONG ; Ting LI ; Chao FANG ; Xue CHEN ; Jun DENG ; Jing WANG ; Nong YANG ; Liang ZENG ; Yongchang ZHANG
Chinese Medical Journal 2025;138(4):478-480

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