1.Research progress on antibody-drug conjugates in the treatment of triple-negative breast cancer
Danna LIU ; Shuangshuang SONG ; Lu CHEN ; Yongqiang SUN ; Bo SUN ; Hanli ZHOU ; Xiaoli ZHAO ; Tiandong KONG
China Pharmacy 2026;37(1):124-129
Antibody-drug conjugates (ADCs) are a novel class of anti-tumor agents composed of a targeted monoclonal antibody, a cytotoxic drug, and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer (TNBC) is characterized by high aggressiveness, elevated risks of recurrence and metastasis, and poor prognosis, largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 (such as trastuzumab deruxtecan), trophoblast cell surface antigen 2 (such as sacituzumab govitecan and datopotamab deruxtecan), zinc transporter LIV-1 (such as ladiratuzumab vedotin), HER-3 (such as patritumab deruxtecan), epidermal growth factor receptor (such as AVID100), and glycoprotein non-metastatic melanoma protein B (such as glembatumumab vedotin) have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities, ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.
2.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.
3.A minimally invasive, fast on/off "odorgenetic" method to manipulate physiology.
Yanqiong WU ; Xueqin XU ; Shanchun SU ; Zeyong YANG ; Xincai HAO ; Wei LU ; Jianghong HE ; Juntao HU ; Xiaohui LI ; Hong YU ; Xiuqin YU ; Yangqiao XIAO ; Shuangshuang LU ; Linhan WANG ; Wei TIAN ; Hongbing XIANG ; Gang CAO ; Wen Jun TU ; Changbin KE
Protein & Cell 2025;16(7):615-620
4.Research Progress on Medical Imaging and New Ultrasound Techniques for Assessing the Degree of Carotid Artery Stenosis
Yigang DU ; Shengli WANG ; Zhaoling LU ; Yanbo LIU ; Yuexin GUO ; Xing AN ; Shuangshuang LI ; Lei ZHU
Chinese Journal of Medical Instrumentation 2024;48(6):624-630
The paper summarizes the imaging evaluation methods for assessing the degree of carotid artery stenosis and analyzes the unique advantages and limitations of various imaging techniques in vascular imaging based on existing guidelines and consensus.The paper focuses on reviewing the clinical applications of several novel ultrasound technologies,including the use of advanced hemodynamic parameters such as blood flow dispersion(Tur index)and wall shear stress(WSS).Carotid artery stenosis is closely associated with cardiovascular disease.Although non-invasive and radiation-free ultrasound technology has certain limitations in diagnostic accuracy to a certain extent,with the continuous emergence of advanced functions such as ultrasound hemodynamics and vascular elasticity,the combination of multi-modality and multi-parameter ultrasound is expected to become an important method for efficient diagnosis of arterial stenosis in the future.
5.Analysis of coping styles of patients with Crohn's disease and its related influencing factors
Huilan ZHAI ; Xueqin LI ; Shan FU ; Shuangshuang XU ; Lu JIANG
Journal of Shenyang Medical College 2024;26(1):58-62
Objective:To investigate the current situation of coping styles in Crohn's disease patients and its related influencing factors.Methods:A total of 80 patients with Crohn's disease admitted to our hospital from Apri 2021 to Dec 2022 were selected to evaluate their coping styles with a simple coping style questionnaire,and relevant data were collected.The factors affecting the coping styles of Crohn's disease were analyzed by multivariable logistic regression.Results:Among the 80 patients,29 cases were negative coping,the incidence was 36.25% .There were 51 patients with positive coping(63.75% ).Educational level,simplified Crohn's disease activity index(CDAI)score,adverse psychology,social support and type D personality were associated with negative coping(P<0.05).Gender,age,family history,working status,monthly family income,place of residence,and marital status were not associated with negative coping in patients with Crohn's disease(P>0.05).Multivariable logistic regression analysis showed that education level of high school or below(OR=2.945,95% CI:1.139-7.614),higher CDAI score(OR=11.999,95% CI:4.387-32.815),poor psychology(OR=5.950,95% CI:2.180-16.239),low social support(OR=3.598,95% CI:1.370-9.448)and type D personality(OR=3.208,95% CI:1.118-8.904)were risk factors for negative coping in patients with Crohn's disease(P<0.05).Conclusions:The incidence of negative coping in patients with Crohn's disease is higher,which is related to high school education or below,high CDAI score,poor psychology,low social support,and type D personality.Therefore,clinical measures can be taken to promote patients to actively cope with the disease.
6.Construction and evaluation of a viral multiplex detection method based on ddPCR for kidney transplantation
Shuangshuang LI ; Jiajin WU ; Xinhua LU ; Min LI ; Muyun WEI
Chinese Journal of Laboratory Medicine 2024;47(9):1067-1072
Objective:To establish a multiplex detection method for monitoring viruses post-kidney transplantation based on droplet digital PCR (ddPCR) technology, evaluate its detection performance, and discuss its potential clinical application.Methods:We developed a ddPCR assay for the simultaneous detection of polyomavirus type 1 virus (BKV), polyomavirus type 2 virus (JCV), and torque teno virus (TTV), assessing its conformity rate, repeatability, and detection limit. 69 clinical urine samples were collected at the Shanghai Jiao Tong University School of Medicine affiliated with Renji Hospital between June and September 2023. The qPCR and ddPCR methods were employed to analyze the results, respectively. Spearman correlation analysis, Bland-Altman analysis, and Wilcoxon paired rank sum test were applied to analyze the detection results of the two methodologies.Results:The constructed ddPCR method had a 7/7 concordance rate for the seven reference samples. The precision reference samples were tested ten times, respectively, and their coefficients of variation were less than 10%. The detection limit was 10 copies/μl. The concordance rates of ddPCR and qPCR for BKV and JCV detection were more than 95% (66/69, 68/69). The correlation coefficients (R) of BKV and JCV viral loads were 0.874 and 0.840, respectively. The Bland-Altman analysis showed that the mean differences in BKV and JCV viral load detection between the two methods were -0.34 and -0.187, respectively. The Wilcoxon paired rank sum test showed that there were no statistically significant differences in the detection results of polyomaviruses between the two methods ( P>0.05). Conclusion:A ddPCR-based multiplex detection method for viruses post-renal transplantation was successfully developed, confirming its superior attributes of high accuracy, high sensitivity, and multi-detection capability. This method could be used for the quantitative detection of BKV, JCV, and TTV in clinical urine samples.
7.Analysis of the construction and practice of an animal biosafety level-3 simulated laboratory
Yushan ZAINAWUDONG ; Xiaoyan LI ; Shuangshuang LU ; Jiaqi WANG ; Aimulajiang KALIBIXIATI ; Mei LIU ; Keliang LIU ; Xuancheng LU
Chinese Journal of Comparative Medicine 2024;34(6):87-92
An animal biosafety level-3 laboratory(ABSL-3)is a high-level biosafety installation that can conduct experiments on animals infected with highly pathogenic microorganisms.In recent years,with the continuous characterization of emerging and re-emerging infectious diseases,high-level biosafety laboratories have played increasingly important roles in pathogenic mechanism and drug and vaccine research and development.The demand for ABSL-3 is increasing year by year.At the same time,there is also a growing demand for personnel who are competent in working in ABSL-3.The systematization,normalization,and standardization of pre-service training have become important to guarantee a reduction in the risks to personnel working in ABSL-3.Training of ABSL-3 staff needs to be carried out in specific simulated laboratories.Therefore,it is necessary to construct simulated ABSL-3 and establish scientific and effective operating standards and mechanisms.This paper comprehensively introduces the design,construction,operation,and functions of a simulated ABSL-3 installation.
8.Diagnostic value of the new optical staining technology for domestic endoscope: a multicenter clinical study
Shuangshuang HAN ; Ruijin WU ; Yifeng LU ; Jing WANG ; Chao LI ; Bo TIAN ; Shihui WANG ; Xin WANG ; Weifang YU ; Feng LIU ; Duanmin HU
Chinese Journal of Digestive Endoscopy 2022;39(4):281-289
Objective:A prospective, multicenter randomized controlled clinical research was conducted to explore the diagnostic value of the new optical staining technology for domestic endoscope, spectral focused imaging (SFI) and variable intelligent staining technology (VIST), for gastric precancerous lesions.Methods:Patients who intended to undergo gastroscopy between August 2020 and May 2021 were randomly divided into the white light group and the new optical staining group at the First Hospital of Hebei Medical University, Shanghai Tenth People's Hospital and the Second Affiliated Hospital of Soochow University. A sequential examination method was applied (white light to new optical staining or new optical staining to white light). The endoscopic diagnostic results and the detection results of Helicobacter pylori ( HP) of the two groups were recorded. At the same time, such five variables as gastric mucosal atrophy, intestinal metaplasia, fold enlargement, nodular gastritis and diffuse redness were evaluated for the risk of gastric cancer in the two groups. Results:A total of 419 cases were enrolled, including 208 cases in the white light group and 211 cases in the new optical staining group. Compared with pathological findings, the detection rates of gastric inflammation, atrophy, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and advanced cancer lesions in the white light group were 28.9%, 40.4%, 64.9%, 17.8%, 0.5% and 0.5% respectively; while those in the new optical staining group were 30.8%, 42.7%, 62.6%, 15.2%, 2.8% and 0.5%. There were no significant differences in the detection rates between the two groups ( P>0.05). Compared with pathology, the sensitivity, the specificity, the accuracy, the positive predictive value and the negative predictive value for gastric mucosal atrophy in the white light group were 92.9%, 61.3%, 74.0%, 61.9% and 92.7% respectively and those in the new optical staining group (SFI mode) were 94.4%, 64.5%, 77.3%, 66.4% and 94.0% respectively. The above 5 measures for gastric mucosal intestinal metaplasia were 68.1%, 72.6%, 69.7%, 82.1% and 55.2% in the white light group, and 87.1%, 89.9%, 88.2%, 93.5% and 80.7% in the new optical staining group (VIST mode), with significant difference between the two groups ( P<0.05). In terms of HP infection with 13C-urea breath test ( 13C-UBT) results as the gold standard, the above 5 measures were 90.2%, 84.3%, 87.4%, 86.8% and 88.2% in the white light group and 92.6%, 77.1%, 85.4%, 82.2% and 90.1% in the new optical staining group respectively. The proportion of high-risk gastric lesions in the new optical staining group was higher in cases of a gastric cancer risk score≥ 4 ( P<0.05). Conclusion:The new optical staining technology of domestic endoscopy has higher diagnostic value for gastric mucosal intestinal metaplasia. Gastroscopy is helpful for the detection of precancerous lesions with gastric cancer risk score as a tool. The new optical staining technology of domestic endoscopy is similar to imported endoscopy in diagnosing gastric precancerous lesions and HP infection, which is an effective means to detect gastric mucosal precancerous lesions.
9.Establishment of Cryosectioning Method and Histochemical Localization Analysis of Volatile Oil and Coumarin Components of Ferula ferulaeoides
Yuanyuan ZHAO ; Ying MA ; Shuangshuang LIU ; Mengmeng LIU ; Xin LU ; Jiaqi YAO ; Siwei ZHANG ; Yun ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(13):161-166
ObjectiveTo establish the frozen section method of Ferula ferulaeoides, and to study the histochemical localization of volatile oil and coumarins in different organs of F. ferulaeoides. MethodThe roots, stems, petioles and leaves of F. ferulaeoides were used as materials to investigate the concentration of sucrose protectant, liquid nitrogen flash-freezing time, embedding conditions, section thickness, freezing temperature and time and post-treatment methods, the most suitable section conditions were screened by comparing the integrity, microscopic effect, elongation and clarity of frozen sections. Sudan Ⅳ staining method and fluorescence microscopy were used to locate the volatile oil and coumarins of F. ferulaeoides. ResultThe optimal conditions for frozen sections of the roots, stems, petioles and leaves of F. ferulaeoides were as follows:10%, 15% and 20% gradient sucrose as the protectant for roots, 10%, 20% and 30% gradient sucrose as the protectant for stems and petioles, 20%, 25% and 30% gradient sucrose as the protectant for leaves, glue-water (2∶1) as the embedding agent, quick-freeze in liquid nitrogen for 20 s, warmed up at -25 ℃ for 30 min, sliced at -20 ℃ with the thickness of 25 μm, rinsed with the same concentration of sucrose solution (gradient sucrose solution selected the last concentration), and the slices placed on the ice pack for a period of time and stored at room temperature. Among them, the concentration of sucrose protectant was the most important factor. The results of histochemical localization showed that volatile oil and coumarins in four organs of F. ferulaeoides were mainly distributed in resin canal. ConclusionFrozen section of F. ferulaeoides is established for the first time with high rate of slicing and simplified steps, its volatile oil and coumarins are mainly accumulated in resin canal.
10.Effects of breast massage at different time periods on lactation yield and breastfeeding success rate
Chinese Journal of Primary Medicine and Pharmacy 2021;28(11):1621-1625
Objective:To investigate the effects of breast massage at different time periods on lactation yield and breast feeding success rate.Methods:240 pregnant women who gave birth at scheduled time in The First People's Hospital of Wenling from January 2018 to May 2019 were included in this study. They were randomly divided into control group, observation group 1 and observation group 2 ( n = 80/group). The control group was only given routine nursing after delivery without breast massage. The observation group 1 received breast massage at 2 hours postpartum based on routine nursing. The observation group 2 received breast massage at 24 hours postpartum based on routine nursing. Breast comfort rate, the time to lactation, lactation yield at 1 and 3 days after intervention were compared between groups. The number of daily vomiting, crying and fecal empties at 4 days postpartum were compared between groups. The success rate of breastfeeding and the increases in neonatal body mass and height at 42 days postpartum were determined in each group. Results:Breast comfort rate in the control group, observation group 1 and observation group 2 was 71.25% (57/80), 93.75% (75/80) and 83.75% (67/80), respectively. There was significant difference in breast comfort rate among the three groups ( χ2 = 26.466, P < 0.05). The incidence of postpartum breast problem in the control group, observation group 1 and observation group 2 was 27.50% (22/80), 5.00% (4/80) and 15.00% (12/80), respectively. There was significant difference in the incidence of postpartum breast problem among the three groups ( χ2 = 10.478, P < 0.05). The time to lactation in the control group, observation group 1 and observation group 2 was (33.54 ± 7.28) hours, (5.56 ± 2.01) hours and (22.32 ± 4.23) hours, respectively ( F = 27.897, P < 0.05). There was significant difference in the time to lactation between groups ( F = 27.897, P < 0.05). The lactation yield in the observation group 1 and observation group 2 was significantly greater than that in the control group ( F = 6.208, 10.458, both P < 0.05). There were significant differences in the number of daily vomiting, crying and fecal empties at 4 days postpartum among the three groups ( F = 71.54, 9.26 and 10.45, all P < 0.05). The success rate of breastfeeding in the observation group 1 was 93.75% (75/80), which was significantly higher than 85.00% (68/80) in the observation group 2 and 75.00% (60/80) in the control group ( χ2 = 7.841, P < 0.05). There were significant differences in the increases in body weight and height of newborns among the three groups at 42 days postpartum ( F = 10.645, 5.789, both P < 0.05). Conclusion:Breast massage at 2 hours postpartum can greatly increase the comfort rate of maternal breast, effectively reduce the incidence of postpartum breast problem, shorten the time to lactation, increase the amount of postpartum lactation yield, and the success rate of breastfeeding.

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