1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Rapid health technology assessment of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus
Huimin PAN ; Yubo WANG ; Huiting SHAN ; Ji CHEN ; Jianhua YANG
China Pharmacy 2025;36(23):2978-2984
OBJECTIVE To evaluate the safety, efficacy, and cost-effectiveness of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for treating type 2 diabetes mellitus (T2DM). METHODS Retrieved databases such as PubMed, Cochrane Library, Embase, CNKI, as well as relevant health technology assessment (HTA) official websites, HTA reports, systematic review/meta- analysis and pharmacoeconomic studies about SGLT-2 inhibitors (including 12 types such as canagliflozin, dapagliflozin, and empagliflozin) in the treatment of T2DM were collected from the inception to January 28, 2025. After literature screening data extraction and quality assessment, a descriptive analysis was conducted on the results of the included studies. RESULTS A total of 38 articles were included, comprising 30 systematic reviews/meta-analyses, 4 pharmacoeconomic studies, and 4 HTA reports. In terms of effectiveness, most research results showed that canagliflozin was effective in controlling blood glucose, reducing body weight, and lowering blood pressure compared to other SGLT-2 inhibitors, while empagliflozin could effectively reduce all-cause mortality. In terms of safety, compared with other SGLT-2 inhibitors, empagliflozin has a lower overall adverse event rate and cardiovascular death risk, canagliflozin presented a higher risk of hypoglycemia, and dapagliflozin had a higher risk of urinary tract infections. In terms of economics, empagliflozin possessed greater economic advantages over both dapagliflozin and canagliflozin, while canagliflozin offered more benefits than dapagliflozin. CONCLUSIONS The selection of SGLT-2 inhibitors for the treatment of T2DM should be individualized. Canagliflozin is recommended for patients with high cardiovascular risk. Empagliflozin boasts the best overall safety profile. Dapagliflozin should be used with caution in patients at high risk of urinary tract infections. Based on foreign economic evidence, empagliflozin has economic advantages. In the future, drug economic studies under the Chinese health system need to be conducted.
3.Forensic performance and genetic background analyses of Guizhou Chuanqing population using a self-constructed microhaplotype panel.
Hongling ZHANG ; Changyun GU ; Qiyan WANG ; Xiaolan HUANG ; Qianchong RAN ; Zheng REN ; Yubo LIU ; Yansha LUO ; Shuaiji PAN ; Meiqing YANG ; Jingyan JI ; Xiaoye JIN
Journal of Southern Medical University 2025;45(7):1442-1450
OBJECTIVES:
To investigate the ethnic origin of Chuanqing people, one of the largest unidentified ethnic groups in Guizhou, China, and analyze its genetic relationships with surrounding populations.
METHODS:
Based on a self-developed microhaplotype system, we conducted genotyping and analyzed the genetic distribution of microhaplotype loci and their forensic applicability in Chuanqing population in Guizhou Province. Using the microhaplotype data from different intercontinental populations and previously reported data from Han population living in Guizhou Province, we systematically investigated the genetic background of Chuanqing people through population genetic approaches, including genetic distance estimation, principal component analysis, and phylogenetic tree construction.
RESULTS:
Among the studied population, the number of haplotype per microhaplotype ranged from 6 to 25. The average expected heterozygosity (He), observed heterozygosity (Ho), power of discrimination (PD), and probability of exclusion (PE) were 0.8291, 0.8301, 0.9387, and 0.6593, respectively. The cumulative power of discrimination (CPD) and cumulative probability of exclusion (CPE) for these 33 loci were 1-2.62×10-41 and 1-7.64×10-17, respectively. Population genetic analyses revealed that the Chuanqing population had close genetic relationships with the East Asian populations, especially the local Guizhou Han population, Beijing Han population and the Han populations living in southern China.
CONCLUSIONS
The 33 microhaplotypes exhibit high levels of genetic diversity in the Guizhou Chuanqing population, highlighting their potentials for both forensic identification and parentage testing. The Han populations might have contributed a significant amount of genetic material to the Chuanqing population during the formation and development of the latter.
Humans
;
China/ethnology*
;
Ethnicity/genetics*
;
Forensic Genetics/methods*
;
Genetics, Population
;
Genotype
;
Haplotypes
;
Phylogeny
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East Asian People/genetics*
4.Mechanism of rheum tanguticum polysaccharide in treating ulcerative colitis induced by trinitrobenzene sulfonic acid
Yubo WANG ; Chenchen GUO ; Gaona LI ; Liying YANG
Chinese Journal of Immunology 2025;41(3):640-643,649
Objective:To investigate the role of rheum tanguticum polysaccharide(RTP)in treating ulcerative colitis(UC)by improving intestinal flora.Methods:UC model was established,rats were divided into normal control group,model group and RTP treatment group.The integrity of colonic mucosa,submucosa and muscularis were observed by HE staining.Expressions of TNF-α,IL-6,IL-8 and IL-1β in serum were assessed by ELISA.16S rRNA sequencing was performed to analyze the composition and differences of intestinal flora in rats.Results:UC rats had symptoms such as loose stools,blood in the stool,anal filth,chills and mental malaise.RTP treatment could significantly improve the symptoms and reduce DAI scores(P<0.05).HE staining showed that the colonic struc-ture of UC rats was necrotic and inflammatory cells infiltrated submucosa.RTP treatment could significantly promote the repair and regeneration of mucosal epithelium.RTP could significantly inhibit inflammatory response and downregulate the expression of inflam-matory factors in UC rats(P<0.05).Composition and abundance of intestinal flora in UC rats were significantly different from that of normal control group.Staphylococcus was significantly increased,while Collinsella,Allobaculum,Chlamydia and Holdemanella were significantly decreased.RTP treatment could improve intestinal flora,reduce the abundance of Staphylococcus,and increase the abundance of Collinsella,Allobaculum,Chlamydia and Holdemanella.Conclusion:RTP can be used to treat UC in rats by inhibiting inflammation and improving intestinal flora.
5.Value of Chinese Group on the Study of Severe Hepatitis B-acute-on-chronic liver failure Ⅱ score in predicting the short-term prognosis of patients with acute-on-chronic liver failure comorbid with hepatic encephalopathy
Tong HUANG ; Yubo ZHAO ; Ling YANG
Journal of Clinical Hepatology 2025;41(8):1615-1619
Objective To investigate the value of Chinese Group on the Study of Severe Hepatitis B-acute-on-chronic liver failureⅡ(COSSH-ACLF Ⅱ)score in predicting the short-term prognosis of patients with hepatitis B virus-related acute chronic liver failure(HBV-ACLF)comorbid with hepatic encephalopathy(HE).Methods A retrospective analysis was performed for 134 patients who were admitted to The First Hospital of Shanxi Medical University from January 2019 to October 2024 and were diagnosed with HBV-ACLF and HE,and according to the survival status of the patients on day 90 of follow-up,they were divided into survival group with 60 patients and death group with 74 patients.Related scores were calculated,including COSSH-ACLF Ⅱ score,COSSH-ACLF score,Model for End-Stage Liver Disease(MELD)score,MELD combined with serum sodium concentration(MELD-Na)score,and MELD 3.0 score,and the two groups were compared in terms of basic clinical data,laboratory markers,complications,and the scores of each model.The chi-square test was used for comparison of categorical data between two groups,and the t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups.The receiver operating characteristic(ROC)curve was used to assess the performance of each score in predicting the prognosis of patients with comorbidity of HBV-ACLF and HE.Results The death group had a significantly higher age than the survival group(56.09±10.52 years vs 49.23±11.57 years,t=2.720,P=0.007).Compared with the survival group,the death group had significantly higher incidence rate of complications(upper gastrointestinal bleeding and ascites)and laboratory markers(white blood cell count,neutrophil count,total bilirubin,international normalized ratio,serum creatinine,and blood urea nitrogen)(all P<0.05).The death group had significantly higher COSSH-ACLF Ⅱ,COSSH-ACLF,MELD,MELD-Na,and MELD 3.0 scores than the survival group(all P<0.001).The patients were stratified into low-,moderate-,and high-risk groups based on COSSH-ACLF Ⅱs score,and comparison between groups showed that the mortality rate of patients increased with the increase in COSSH-ACLF Ⅱ score(χ2=44.371,P<0.001).The ROC curve analysis showed that COSSH-ACLF Ⅱ score had an area under the ROC curve(AUC)of 0.883(95%confidence interval:0.837-0.919)in predicting the 90-day mortality of patients with comorbidity of HBV-ACLF and HE,with a sensitivity of 90.5%,a specificity of 78.7%,and a predictive accuracy of 85.07%at the cut-off value of 7.25.COSSH-ACLF Ⅱscore had a better performance than COSSH-ACLF(AUC=0.841,P<0.05),MELD 3.0(AUC=0.733,P<0.05),MELD-Na(AUC=0.723,P<0.05),and MELD(AUC=0.716,P<0.05).Conclusion COSSH-ACLF Ⅱ score can improve the accuracy of predicting 90-day prognosis in patients with comorbidity of HBV-ACLF and HE,and COSSH-ACLF Ⅱ risk stratification can help to simplify the grading of patients.
6.Research on the design and application value of a simulation system for surgical operation based on virtual reality technique and intelligent scoring function
Long LI ; Qingbo WANG ; Yubo LIANG ; Jin LI ; Wanling LUO ; Xingming CHEN ; Yang DUAN ; Zhiyi TANG ; Shengjie NIE ; Yang KE
China Medical Equipment 2025;22(5):28-32
Objective:To design a set of simulation system for surgical operation based on virtual reality(VR)technique and intelligent scoring functions,so as to assess its clinical application effect.Methods:The Digital Imaging and Communications in Medicine(DICOM)images of typical patients were collected.Materialise Interactive Medical Image Control System(MIMICS)software was adopted to reconstruct the three-dimensional(3D)model of diseased organs.Surgical instrument models were constructed by using 3D Max software.Unity 3D software was adopted to construct simulation system for surgical operation with VR+intelligent scoring.A total of 40 surgical resident physicians,who were employed with 3 years since 2019 in The Second Affiliated Hospital of Kunming Medical University,were selected.They were divided into observation group and control group,with 20 cases in each group.The observation group used simulation system for surgical operation to conduct intelligent scoring for cholecystectomy under laparoscope,and the control group used conventional scoring for surgical operation.The scores of surgical operation and test between the two groups were compared.Results:The mean value of surgical operation time of the observation group was(1.72±0.41)h,and the average incidence of complication was(0.03±0.02)%,both of them of the observation group were significantly lower than those of the control group[(2.25±0.42)h and(0.05±0.03)%].The differences of them between two groups were statistically significant(t=9.00,4.08,P<0.05).The test scores of surgical operation of the observation group was also significantly higher than that of the control group(t=5.26,P<0.001).Conclusion:The developed simulation system for surgical operation with VR+intelligent scoring can significantly enhance users'surgical operation skills and improve learning outcomes,which has favorable prospects in future applications.
7.Application Progress of Lipidomics in Diabetic Nephropathy
Zhengwei DONG ; Kang YANG ; Yubo LI ; Huan ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):321-328
Diabetic nephropathy(DN)is a chronic complication that leads to the high mortality of diabetes mellitus(DM)patients.Many researchers are devoted to the diagnosis,etiology,process and molecular mechanism of treatment of DN.At present,the regulation of small molecular lipids on renal function and the role in the pathogenesis of DN are gradually becoming clear,and lipidomics has also become a powerful tool in DN research.DN is characterised by disorders of lipid metabolism,and lipidomics plays an important role in the characterisation of lipid metabolic profiles,diagnosis,mechanistic investigation and treatment of DN because of its unique relevance.But at the same time,the lipids in the body are complex,which brings great challenges to the detection and analysis of lipids.In the future,multidisciplinary crossover and multi-omics association is the direction of lipidomics breakthrough.This article outlines the progress of the application of lipidomics in DN research strategies,lipid metabolic profiling,early diagnosis,drug efficacy and mechanism exploration,and histological co-analysis,and further discusses the opportunities and challenges of the future application of lipidomics in DN,with the aim of providing a clear picture of the current status of the research and the prospects for researchers in the relevant directions.
8.Cost-utility analysis of semaglutide versus canagliflozin in patients with type 2 diabetes poorly controlled with metformin
Yueru XU ; Yubo WANG ; Huimin PAN ; Huiting SHAN ; Ji CHEN ; Jianhua YANG
China Pharmacy 2025;36(9):1087-1092
OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus(T2DM)poorly controlled with metformin. METHODS Based on the perspective of China’s health system, a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio(ICER) and incremental net monetary benefit (INMB) were calculated using one time the 2024 per capita gross domestic product(GDP) as the willingness-to-pay(WTP) threshold. One-way sensitivity analysis, probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin, ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year (QALY),which was higher than the WTP threshold set in this study (95 749 yuan/QALY),and the corresponding INMB was -61 576.24 yuan,indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB,but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold,the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold,the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system, canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.
9.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.

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