1.CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer.
Yuncheng BEI ; Sijie WANG ; Rui WANG ; Owais AHMAD ; Meng JIA ; Pengju YAO ; Jianguo JI ; Pingping SHEN
Acta Pharmaceutica Sinica B 2025;15(3):1608-1625
Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.
2.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
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.
3.Nursing care for a patient with extremely severe obese and multiple myeloma complicated with status epilepticus
Xiaobai CAO ; Pengju WANG ; Lan GAO ; Yujiao WANG
Chinese Journal of Nursing 2025;60(17):2145-2149
To summarize the nursing care for a patient with extremely severe obese and multiple myeloma complicated with status epilepticus.The key points of nursing include:a multidisciplinary rescue team was established to accurately and comprehensively assess the patient's obesity level;based on the degree of obesity,a goal-directed sedation and analgesia strategy was implemented;airway management measures were optimized for difficult intubation,and lung-protective ventilation strategies were strictly followed with adjusted mechanical ventilation parameters;implementing precise fluid management,closely monitoring electrolyte levels,and reducing triggers for seizure episodes;sequential nutrition support combined with trophic feeding was provided,along with personalized enteral nutrition;early mobilization was initiated to prevent deep vein thrombosis;a skin protection strategy was implemented to establish a safe skin barrier.After meticulous treatment and nursing care,the patient's condition improved,and she was discharged.
4.Hepatic nontargeted lipidomics study for mechanism of Shaqi concen-trated pills attenuating high-fat diet-induced metabolic dysfunction-asso-ciated fatty liver disease in mice
Shuyin BAO ; Xuan WANG ; Pengju BAI ; Qiong WU ; Qianqian MA
Chinese Journal of Pathophysiology 2025;41(8):1504-1513
AIM:This study aimed to investigate the differences in hepatic lipid metabolites in ICR mice in-duced by a high-fat diet and treated with Shaqi concentrated pills(SQ).METHODS:Thirty 8-week-old SPF-grade ICR mice were randomly assigned to five groups:the normal(CON,n=6)group,the high-fat diet model(HFD,n=6)group,the low-dose SQ administration(SQL,n=6)group,the high-dose SQ administration(SQH,n=6)group,and the liver-protecting tablets positive control(PLT,n=6)group.The HFD group was fed a diet consisting of 60%fat for 8 weeks to es-tablish a metabolic-dysfunction-associated fatty liver disease model.Upon successful model establishment,the SQL group received a daily gavage of 395 mg/kg for 4 weeks,while the SQH group received 790 mg·kg-1·d-1.The PLT group was ad-ministered liver-protecting tablets at a dosage of 0.655 g/kg via gavage.Body weight and food intake were monitored week-ly.Liver indices,including Lee's index,triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),and aspartate transaminase(AST)levels,were measured in each group.Hematoxylin-eosin(HE)staining and oil red O staining were performed to assess the extent of pathological damage in liver tissues.Western blot analysis was conducted to evaluate the protein expres-sion levels of choline/ethanolamine phosphotransferase-1(CEPT1),adipose triglyceride lipase(ATGL),and diacylglycerol acyltransferase(DGAT)in the liver.A non-targeted lipidomic analysis using LC-MS was employed to detect changes in hepatic lipid content,and multivariate statistical analyses(principal component analysis and orthogonal partial least squares discriminant analysis)were utilized to compare lipid metabolic profiles among the groups and identify differential lipid metabolites.RESULTS:Compared to the CON group,mice in the HFD group exhibited significantly increased body weight,blood glucose levels,serum TG,TC,LDL-C,ALT,and AST levels,accompanied by a marked decrease in HDL-C levels.HE and oil red O staining results revealed significant lipid droplet accumulation in the liver tissues of HFD mice.In contrast,mice in the SQL and SQH groups showed significant reductions in body weight,blood glucose,serum TG,TC,LDL-C,ALT,and AST levels,along with increased HDL-C levels and less lipid accumulation in liver tissues compared to the HFD group.Staining of liver sections confirmed that SQ treatment mitigated the abnormal accumulation of lipid droplets.Lipidomic analysis indicated that SQ treatment normalized 25 aberrantly expressed lipid metabolites to lev-els comparable to the CON group and identified nine representative differential lipid metabolites.Western blot results dem-onstrated that SQ treatment reduced the protein expression levels of ATGL and DGAT while increasing the expression of CEPT1.CONCLUSION:Treatment with SQ can alleviate metabolic dysfunction-associated fatty liver disease(MAFLD)by modulating triglyceride metabolism,phosphatidylcholine metabolism,and dimethylphosphatidylethanolamine lipid me-tabolism,thereby altering the hepatic lipid profile in MAFLD mice.
5.Cross-border high-quality clinical nutrition internship program for Hong Kong college students at the Department of Clinical Nutrition of Peking Union Medical College Hospital
Rongrong LI ; Fumin HUANG ; Kang YU ; Fang WANG ; Wei CHEN ; Yanping LIU ; Junren KANG ; Wenyan SUN ; Pengju LIU ; Jin FU ; Peipei CHEN ; Wei WEI
Chinese Journal of Clinical Nutrition 2025;33(4):311-314
Cross-border teaching provides new opportunities for college students to gain diverse insights amid the globalization and internationalized education, In July 2024, guided by the Chinese Association for Science and Technology, the Chinese Nutrition Society and the Hong Kong Nutrition Association collaborated to host a three-week clinical nutrition internship at Peking Union Medical College Hospital for five college students from Hong Kong SAR, China. This program included participating in outpatient rounds, attending in inpatient nutrition management, and attending lectures, aiming to enhance students' professional skills and clinical experience. Cultural exchange and value-based education also enriched students' social responsibility and cultural understanding. The Hong Kong students also brought diverse cultural backgrounds and inputs, enabling multidimensional communication during the training. Post-internship feedback survey showed that the students found the inernship valuable for their career development and hoped for more learning opportunities. This cross-border high-quality internship program fostered skill enhancement, cultural exchange between young students in Beijing and Hong Kong and contributed to advancement of clinical nutrition.
6.Impact of cancer-specific foods for special medical purposes on nutritional adequacy, safety, and efficacy in postoperative cancer patients
Fang WANG ; Pengju LIU ; Rongrong LI ; Jin FU ; Wei WEI ; Kang YU
Chinese Journal of Clinical Nutrition 2025;33(4):266-274
Objective:To evaluate the impact of a high-energy-density, high-protein, immune-modulating, cancer-specific foods for special medical purposes (FSMP) on nutritional adequacy, safety, and efficacy in postoperative cancer patients.Methods:This multicenter randomized controlled trial enrolled patients with gastrointestinal or head and neck cancer scheduled for surgery and at nutritional risk. Participants were randomized 1∶1 to receive either the investigational cancer-specific FSMP (FSMP group) or a commercially available tumor-specific enteral nutrition (EN) formula (control group). The "nutritional transition phase" (postoperative days 0-3) provided the assigned EN, with energy deficits supplemented by parenteral nutrition (PN). This was followed by the "full EN phase" (intervention period: 10±3 days), with a target energy intake of 105-146 kJ/kg/day. Nutritional adequacy was considered achieved if the actual intake reached ≥80% of the target in both phases. The primary outcomes were the body weight and prealbumin improvement rates after intervention , and the secondary outcomes were the improvement rates of handgrip strength, gait speed, serum albumin, and hemoglobin. Non-inferiority was tested using the confidence intervals, with the least squares mean difference and its 95% CI derived from a Logistic regression model (non-inferiority margin: -0.12).Results:A total of 220 patients from 17 centers completed the study (FSMP group: n=109; control group: n=111). After the nutrition support, the weight loss was (-0.9±2.1) kg and (-1.3±1.8) kg in the FSMP and control groups ( P=0.162), whereas prealbumin increased in both groups (59.0±69.0 mg/L vs. 50.0±62.0 mg/L, P=0.418). The lower bounds of the 95% CIs were -0.08 for both weight and prealbumin improvement rates, exceeding the predefined non-inferiority margin (-0.12). No significant differences were observed in the improvements in albumin, hemoglobin, handgrip strength, or gait speed (all P>0.05). No serious adverse events related to the formulas occurred. The FSMP group had a higher incidence of diarrhea (31.9% vs. 17.8%) and lower compliance rate (<80% intake: 13.4% vs. 5.9%), but the percentages of total energy intake over the estimated energy requirements (% of target) were comparable (89.9%±24.5% vs. 94.0%±22.3%, P=0.310). Conclusions:The cancer-specific FSMP can improve postoperative nutritional status in cancer patients, demonstrating non-inferiority to existing tumor-specific EN formulas in terms of nutritional adequacy, safety, and efficacy.
7.Cross-border high-quality clinical nutrition internship program for Hong Kong college students at the Department of Clinical Nutrition of Peking Union Medical College Hospital
Rongrong LI ; Fumin HUANG ; Kang YU ; Fang WANG ; Wei CHEN ; Yanping LIU ; Junren KANG ; Wenyan SUN ; Pengju LIU ; Jin FU ; Peipei CHEN ; Wei WEI
Chinese Journal of Clinical Nutrition 2025;33(4):311-314
Cross-border teaching provides new opportunities for college students to gain diverse insights amid the globalization and internationalized education, In July 2024, guided by the Chinese Association for Science and Technology, the Chinese Nutrition Society and the Hong Kong Nutrition Association collaborated to host a three-week clinical nutrition internship at Peking Union Medical College Hospital for five college students from Hong Kong SAR, China. This program included participating in outpatient rounds, attending in inpatient nutrition management, and attending lectures, aiming to enhance students' professional skills and clinical experience. Cultural exchange and value-based education also enriched students' social responsibility and cultural understanding. The Hong Kong students also brought diverse cultural backgrounds and inputs, enabling multidimensional communication during the training. Post-internship feedback survey showed that the students found the inernship valuable for their career development and hoped for more learning opportunities. This cross-border high-quality internship program fostered skill enhancement, cultural exchange between young students in Beijing and Hong Kong and contributed to advancement of clinical nutrition.
8.Impact of cancer-specific foods for special medical purposes on nutritional adequacy, safety, and efficacy in postoperative cancer patients
Fang WANG ; Pengju LIU ; Rongrong LI ; Jin FU ; Wei WEI ; Kang YU
Chinese Journal of Clinical Nutrition 2025;33(4):266-274
Objective:To evaluate the impact of a high-energy-density, high-protein, immune-modulating, cancer-specific foods for special medical purposes (FSMP) on nutritional adequacy, safety, and efficacy in postoperative cancer patients.Methods:This multicenter randomized controlled trial enrolled patients with gastrointestinal or head and neck cancer scheduled for surgery and at nutritional risk. Participants were randomized 1∶1 to receive either the investigational cancer-specific FSMP (FSMP group) or a commercially available tumor-specific enteral nutrition (EN) formula (control group). The "nutritional transition phase" (postoperative days 0-3) provided the assigned EN, with energy deficits supplemented by parenteral nutrition (PN). This was followed by the "full EN phase" (intervention period: 10±3 days), with a target energy intake of 105-146 kJ/kg/day. Nutritional adequacy was considered achieved if the actual intake reached ≥80% of the target in both phases. The primary outcomes were the body weight and prealbumin improvement rates after intervention , and the secondary outcomes were the improvement rates of handgrip strength, gait speed, serum albumin, and hemoglobin. Non-inferiority was tested using the confidence intervals, with the least squares mean difference and its 95% CI derived from a Logistic regression model (non-inferiority margin: -0.12).Results:A total of 220 patients from 17 centers completed the study (FSMP group: n=109; control group: n=111). After the nutrition support, the weight loss was (-0.9±2.1) kg and (-1.3±1.8) kg in the FSMP and control groups ( P=0.162), whereas prealbumin increased in both groups (59.0±69.0 mg/L vs. 50.0±62.0 mg/L, P=0.418). The lower bounds of the 95% CIs were -0.08 for both weight and prealbumin improvement rates, exceeding the predefined non-inferiority margin (-0.12). No significant differences were observed in the improvements in albumin, hemoglobin, handgrip strength, or gait speed (all P>0.05). No serious adverse events related to the formulas occurred. The FSMP group had a higher incidence of diarrhea (31.9% vs. 17.8%) and lower compliance rate (<80% intake: 13.4% vs. 5.9%), but the percentages of total energy intake over the estimated energy requirements (% of target) were comparable (89.9%±24.5% vs. 94.0%±22.3%, P=0.310). Conclusions:The cancer-specific FSMP can improve postoperative nutritional status in cancer patients, demonstrating non-inferiority to existing tumor-specific EN formulas in terms of nutritional adequacy, safety, and efficacy.
9.Nursing care for a patient with extremely severe obese and multiple myeloma complicated with status epilepticus
Xiaobai CAO ; Pengju WANG ; Lan GAO ; Yujiao WANG
Chinese Journal of Nursing 2025;60(17):2145-2149
To summarize the nursing care for a patient with extremely severe obese and multiple myeloma complicated with status epilepticus.The key points of nursing include:a multidisciplinary rescue team was established to accurately and comprehensively assess the patient's obesity level;based on the degree of obesity,a goal-directed sedation and analgesia strategy was implemented;airway management measures were optimized for difficult intubation,and lung-protective ventilation strategies were strictly followed with adjusted mechanical ventilation parameters;implementing precise fluid management,closely monitoring electrolyte levels,and reducing triggers for seizure episodes;sequential nutrition support combined with trophic feeding was provided,along with personalized enteral nutrition;early mobilization was initiated to prevent deep vein thrombosis;a skin protection strategy was implemented to establish a safe skin barrier.After meticulous treatment and nursing care,the patient's condition improved,and she was discharged.
10.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

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