1.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.
2.18F-FDG PET/CT metabolic parameters for prediction of treatment response to neoadjuvant immunochemotherapy in locally advanced gastric cancer
Peng LI ; Shuang LU ; Weiwei ZHAO ; Yanmei LI ; Xianhua HAN ; Xiaofeng ZHANG ; Jianwei YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(11):648-653
Objective:To investigate the value of midtreatment 18F-FDG PET/CT metabolic parameters for predicting the pathological response in patients with locally advanced gastric cancer (LAGC) after neoadjuvant immunochemotherapy (NICT). Methods:Twenty-five LAGC patients (19 males, 6 females, age: (64.8±8.6) years) who underwent 18F-FDG PET/CT after NICT in Henan Cancer Hospital from August 2019 to June 2024 were retrospectively analyzed. The lesion′s ROI was delineated, then the SUV max and metabolic tumor volume (MTV) were measured, and the SUV max was divided by SUV mean of the descending aorta to obtain the tumor-to-background ratio (TBR). Patients underwent surgery after PET/CT imaging. Based on the tumor regression grade (TRG) system by the American Joint Committee on Cancer (AJCC) criteria on surgical specimen, patients were divided into responders (TRG0+ 1) and non-responders (TRG2+ 3). Independent-sample t test, Mann-Whitney U test, one-way analysis of variance, and Kruskal-Wallis rank-sum test were used to compare the differences of data. The predictive efficacy of PET/CT metabolic parameters was assessed by the ROC curve analysis. Results:Postsurgical pathology showed that 9 patients were responders and 16 were non-responders. The SUV max (3.10±1.95) and TBR (2.44±1.54) of primary lesions in responders were lower than those in non-responders (7.40±4.68, 5.85±3.74; t values: -2.61, -2.59, both P<0.05), while the MTV of primary tumors and short diameter and metabolic parameters of positive lymph nodes were not significantly different between those 2 groups ( t=-1.50, Z values: -1.09 to -0.75, all P>0.05). No significant relation was found between PET/CT parameters and pathological differentiation or Lauren classification, or other pathological features ( t values: -1.55 to 1.38, Z values: -1.84 to 0, F values: 0.12-2.43, H values: 0.13-0.98, all P>0.05). ROC curve showed that the cut-off value of SUV max for predicting postoperative TRG was 5.40, and the AUC reached 0.77 (95% CI: 0.56-0.91), with the sensitivity and specificity of 9/16, 9/9, respectively. With TBR=3.54 as the cut-off value, its AUC reached 0.77 (95% CI: 0.56-0.91), and the sensitivity and specificity were 11/16, 8/9, respectively. The sensitivity and specificity of PET/CT for predicting lymph node positivity of patients were 8/12 and 13/13, respectively. Conclusion:Interim 18F-FDG PET/CT metabolic parameters can accurately predict the pathological response of LAGC patients after NICT.
3.Analysis of hotspots and trends in traditional Chinese medicine treatment of neurogenic bladder based on bibliometrics and knowledge graph
Xiaoxiao SHI ; Yang CHEN ; Linlin MA ; Xue YANG ; Jianwei SHI ; Qianqian ZHANG ; Yuan LU
Chinese Journal of General Practitioners 2025;24(2):190-197
Objective:To analyze the current research hotspots and trends of traditional Chinese medicine (TCM) treatment for neurogenic bladder (NB).Methods:The Chinese and English articles on TCM treatment of neurogenic bladder were searched in CNKI, Wanfang Database, PubMed, and Web of Science from the inception to May 31, 2024, using the terms "neurogenic bladder" "intervention" "treatment" "clinical" "Chinese medicine" "electroacupuncture" "acupuncture", and "moxibustion". VOSviewer and Citespace bibliometric software were used to analyze the publication trend, authors, research institutions, source journals and keywords of these articles.Results:A total of 776 Chinese articles and 253 English articles on the diagnosis and treatment of NB by traditional Chinese medicine were retrieved, the number of publications was increasing every year. Most Chinese papers came from Shandong University of Traditional Clinese Medicine, and most English papers came from Sun Yat-sen University. Some authors and institutions had formed networks of cooperation. Most papers were published in the journal of Traditional Chineses Medicine Clinical Research (in Chinese) and Neural Regeneration Research (in English). This study generated 244 Chinese core key words with 14 clustering networks, and 233 English core key words with 10 clustering networks. The main symptoms of NB are uroschesis and urinary incontinence. NB are primarily caused by spinal cord injury, diabetes mellitus and stroke. The main treatment methods of TCM for NB are electroacupuncture, acupuncture and percutaneous acupoint electrical stimulation. The research on NB mechanisms focuses on the apoptosis, regeneration and plasticity of spinal neurons, the activation of the bladder autophagy signaling pathway, the expression of proteins related to the contractile function of the forced muscles. Conclusion:The research quantity and quality of traditional Chinese medicine in diagnosis and treatment NB have increased in recent years, and the mechanism and treatment of NB are the research hotspots; however, the extension and depth of researches are limited, and the institutional cooperations are insufficiente.
4.Single-cell sequencing reveals heterogeneity of B cells in osteoporosis patients and their interactions with osteoblasts
Zhi TANG ; Yang SHAO ; Shaoshuo LI ; Shubin QI ; Hengyang LU ; Mao WU ; Junfeng YANG ; Jianwei WANG
Chinese Journal of Tissue Engineering Research 2025;29(26):5501-5510
BACKGROUND:The pathogenesis of osteoporosis is closely related to the immune system.A comprehensive and in-depth study of the relationship between immunity and osteoporosis is crucial for understanding and treating the disease.OBJECTIVE:To investigate the role of immune cells in osteoporosis using single-cell sequencing technology.METHODS:Femoral head tissue samples from osteoporosis and non-osteoporosis patients were downloaded from GEO database and analyzed using single-cell sequencing.Data analysis,including cell clustering,functional enrichment,pseudotime trajectory,and cell interaction analyses,was performed using R4.3.0 and software packages such as Seurat v.4.3,monocle(2.28.0),and CellChat.The femoral head tissues of patients with femoral neck fracture who underwent artificial hip replacement surgery were obtained,including two cases of osteoporosis patients and two cases of non-osteoporosis patients.Immunohistochemical staining was used to detect the protein expression of CCL13 and CCL18.qPCR was used to detect the immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA expression.Western blot was used to detect the protein expression of receptor-type tyrosine protein phosphatase C,CD22,and CD99.RESULTS AND CONCLUSION:Transcriptomic analysis identified 10 cell clusters,including osteoclasts,myeloid cells,T cells,osteoblasts,macrophages,monocytes,erythrocytes,B cells,bone marrow mesenchymal stem cells,and mast cells.There was an increase in the ratio of osteoclasts to T cells and a decrease in the ratio of osteoblasts to B cells in the femoral head tissue of the osteoporosis group.Among the B-cell subpopulations,the proportion of B-cells of taxa 1,3(BC1,BC3)in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,and the proportion of B-cells of taxa 2(BC2)was less than that of the non-osteoporosis group.BC1 was enriched significantly for labels such as regulation of adaptive immune response,somatic recombination of immune receptors,and modulation of lymphocyte-mediated immunity,while BC3 was enriched significantly for labels such as regulation of immunoglobulin production,response to type Ⅱ interferon,apoptotic processes involving cysteine endopeptidases,and cytotoxicity.The communication intensity between B-cell subtype BC1 and osteoblasts in the femoral head tissue of the osteoporosis group was higher than that of the non-osteoporosis group,while the communication intensity between BC3 and BC1 was also increased.The communication between BC3 and BC1 was significantly enriched in the CD22-receptor-type tyrosine protein phosphatase C pathway;the communication between BC1 and osteoblasts was mainly enriched in the CD99-CD99 pathway;and the communication between BC3 and osteoblasts was also highly enriched in the CD99-CD99 pathway.Protein expression of CCL13,CCL18,receptor-type tyrosine protein phosphatase C,CD22,CD99,immunoglobulin heavy constant γ-4,immunoglobulin λ constant 3,human class Ⅱ major histocompatibility complex DRβ1,and CD83 mRNA were higher in femoral tissues of the osteoporosis group than those of the non-osteoporosis group(P<0.05).To conclude,specific B cell subpopulations can influence the differentiation and apoptosis of osteoblasts in the femoral tissue of osteoporosis patients.
5.Research progress in hydrogels in tissue engineering trachea
Wenxuan CHEN ; Yibo SHAN ; Fei SUN ; Zhiming SHEN ; Yi LU ; Jianwei ZHU ; Lei YUAN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1195-1199
In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.
6.Increasing trends of hyperglycemia and diabetes in treatment-naive people living with HIV in Shenzhen from 2013 to 2019: An emerging health concern.
Liqin SUN ; Haipeng ZHU ; Man RAO ; Fang ZHAO ; Yang ZHOU ; Lukun ZHANG ; Xia SHI ; Jianwei WU ; Yun HE ; Hongzhou LU ; Jiaye LIU
Chinese Medical Journal 2025;138(16):2043-2045
7.Clinical application of Wei nasal jet tube in general anesthesia induction in patients with extensive facial burns
Fusheng XU ; Yuanyuan WEI ; Qiufen WANG ; Jianwei XIAO ; Xiaohong LIU ; Jingjia YAN ; Qingwang LU ; Jianshui LIN
Journal of Chongqing Medical University 2025;50(11):1573-1577
Objective:To observe the effectiveness and safety of the application of Wei nasal jet tube(WNJT)in anesthesia induction for patients with extensive facial burns.Methods:A total of 60 patients who underwent multiple systemic scab removal and skin graft-ing surgery in our hospital from July 2021 to July 2023 were enrolled in this study.The patients were 18-60 years of age,with a body mass index of 18-29 kg/m2,ASA II or III,and Mallampati I-III.Using a random number table method,the patients were divided into WNJT ventilation group(W group)and mask ventilation group(M group),with 30 cases in each group.Before anesthesia induction,WNJT was inserted into one side of the nasal cavity for hand controlled normal frequency supraglottic jet ventilation in group W pa-tients,while oxygen ventilation was administered to group M patients through conventional two-hand clasped face masks.After 5 min,tracheal intubation was performed under a visual laryngoscope.The mean amplitude of diaphragm fluctuations,end expiratory carbon dioxide partial pressure(PETCO2),and blood oxygen saturation(SpO2)measured by ultrasound were recorded during spontaneous respi-ration at 5 min of oxygenation and nitrogen removal(T0),as well as at 1 min(T1),2 min(T2),3 min(T3),4 min(T4),and 5 min(T5,im-mediately before intubation)of anesthetic induction.Arterial blood gas(PaO2 and PaCO2)at T0 and T5 were measured.Heart rate(HR)and mean arterial pressure(MAP)were recorded at T0-T5 in both groups of patients.The occurrence of postoperative pharyngeal pain,facial or mandibular angle bleeding,gastrointestinal bloating,and nasal mucosal bleeding were recorded in both groups of pa-tients.Results:At T0,there were no statistically significant differences in mean amplitude of diaphragm fluctuations,HR,MAP,PaO2,PaCO2,PETCO2,and SpO2 between the two groups of patients.At T1-T5,the HR and MAP of patients in the W group were significantly lower than those in the M group(P<0.05).At T5,the PaO2 of patients in the W group was significantly higher than that in the M group,while the PaCO2 and PETCO2 were significantly lower than those in the M group(P<0.05).However,the difference in SpO2 was not sta-tistically significant.The W group had less facial or mandibular angle bleeding and postoperative gastrointestinal bloating than the M group,and the differences were statistically significant(P<0.05).There were no statistically significant differences between the two groups of patients in postoperative pharyngitis and nasal mucosal bleeding(P>0.05).Conclusion:During general anesthesia induction in patients with extensive facial burns,WNJT has the advantages of good ventilation effect,high safety,less complications such as gas-trointestinal bloating and facial or mandibular angle bleeding,and more stable hemodynamics.WNJT has good application prospects in clinical anesthesia.
8.Design and application of a height measuring instrument for ventricular drainage catheter.
Qingchen ZHAI ; Guanjie CHEN ; Jianwei LI ; Junping LI ; Lu MA
Chinese Critical Care Medicine 2025;37(3):294-296
Ventriculostomy drainage is one of the commonly used surgical techniques in neurocritical care, which can relieve intracranial hypertension and facilitate postoperative cerebrospinal fluid and intracranial pressure monitoring. By placing a drainage tube in the ventricle, blood and fluid accumulation within the ventricle are drained out of the brain, reducing intracranial pressure and preventing brain tissue damage. Clinically, the speed of ventriculostomy drainage is often controlled by measuring the height difference between the drainage opening and the plane of the ventricle, ensuring the safe and effective reduction of intracranial pressure, facilitating the implementation of clinical management plans, and preventing complications. However, how to easily, safely, and effectively measure the height difference between the drainage opening and the ventricular plane remains a challenge in nursing management. Currently, clinical practice often uses a tape measure to measure the height of the ventriculostomy drainage, a process that is cumbersome and time-consuming and susceptible to human error, leading to inaccurate measurements. However, the challenge of easily, safely, and effectively detecting the height difference between the drainage opening and the ventricular plane remains a difficult problem in nursing management. To address this issue, the medical and nursing staff of the intensive care unit (ICU) at Zhongda Hospital, Southeast University, jointly designed a novel ventriculostomy drainage height measurement device, which has been granted a national utility model patent (patent number: ZL 2022 2 1400920.9). This device can be easily and securely fixed to an infusion stand. Using a level within the horizontal measuring part and a rotational structure, the vertical measuring part of the device is adjusted to be perpendicular to the ground. After opening the limit clip, the horizontal part is manually guided down to the appropriate height. The front end of the horizontal measuring part is then extended towards the patient's head, and after confirming the position, the limit clip is closed. At this point, the horizontal height difference between the drainage opening and the ventricular plane can be accurately measured. When temporarily finishing the height measurement of the drainage tube, the device can be folded and stored by retracting the horizontal measuring part and rotating components. This measuring device has a simple operation process, which can improve the accuracy and reliability of the drainage height measurement, enhance treatment outcomes and patient safety, reduce the workload of nursing staff, and has certain clinical promotion and practical value.
Humans
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Ventriculostomy/methods*
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Drainage/instrumentation*
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Equipment Design
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Cerebral Ventricles
9.Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: the initial results of a randomized controlled clinical trial (STELLAR II)
Haoyue LI ; Haitao ZHOU ; Lichun WEI ; Yinggang CHEN ; Wenjue ZHANG ; Feiyan DENG ; Ning LI ; Zheng JIANG ; Zheng LIU ; Jianwei LIANG ; Zhaoxu ZHENG ; Xianyu MENG ; Yufei LU ; Zifa LEI ; Xiaoge SUN ; Gong LI ; Yingjie WANG ; Yongwen SONG ; Shunan QI ; Hao JING ; Yirui ZHAI ; Shulian WANG ; Yexiong LI ; Yuan TANG ; Jing JIN
Chinese Journal of Oncology 2025;47(9):913-921
Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.
10.Establishment of a nomogram model for predicting pelvic lymph node metastasis in prostate cancer based on systemic immune-infiltration inflammation index
Junzhi LIU ; Lei QIU ; Kun XU ; Jianwei LIU ; Dehua HU ; Hua ZHU ; Cheng SHEN ; Ming LU ; Jiangang CHEN
The Journal of Practical Medicine 2025;41(15):2349-2354
Objective To develop and validate a nomogram model that integrates systemic inflammatory markers to predict the likelihood of pelvic lymph node metastasis(PLNM)in prostate cancer patients prior to surgery.Methods This study retrospectively analyzed the clinical data and preoperative inflammatory markers—including neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),and monocyte-to-lymphocyte ratio(MLR)—of patients diagnosed with prostate cancer.Univariate and multi-variate logistic regression analyses were conducted to identify markers that were significantly associated with PLNM.Based on the results of the multivariate analysis,a nomogram was developed and its predictive accuracy was assessed using receiver operating characteristic curves(ROC)and calibration plots.Results Among the 334 enrolled patients with prostate cancer,107 were identified with PLNM.Univariate analysis revealed statistically significant differences in free prostate-specific antigen(fPSA),Gleason score,NLR,PLR,MLR,and SII between the PLNM and non-pelvic lymph node metastasis(NPLNM)groups(P<0.05).Multivariate analysis confirmed that fPSA,Gleason score,and SII were independent predictors of PLNM(P<0.05).A nomogram incorporating these predic-tors exhibited strong discriminative ability,with an area under the ROC curve(AUC)of 0.79(95%CI:0.73~0.84).Calibration analysis further demonstrated good consistency between the predicted and observed probabilities of PLNM.Conclusions This study successfully developed a nomogram model based on systemic inflammatory markers for preoperative prediction of pelvic lymph node metastasis in prostate cancer.Owing to its user-friendly design and high predictive accuracy,this tool may serve as a valuable complementary method to conventional imaging techniques,thereby supporting personalized treatment decision-making.

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