1.Evaluating the impact of relative dose intensity on efficacy of trastuzumab deruxtecan for metastatic breast cancer in the real-world clinical setting.
Han Yi LEE ; Vivianne SHIH ; Jack Junjie CHAN ; Shun Zi LIONG ; Ryan Shea Ying Cong TAN ; Jun MA ; Bernard Ji Guang CHUA ; Joshua Zhi Chien TAN ; Chuan Yaw LEE ; Wei Ling TEO ; Su-Ming TAN ; Phyu NITAR ; Yoon Sim YAP ; Mabel WONG ; Rebecca DENT ; Fuh Yong WONG ; Tira J TAN
Annals of the Academy of Medicine, Singapore 2025;54(8):458-466
INTRODUCTION:
Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges.
METHOD:
Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes.
RESULTS:
Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities.
CONCLUSION
Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans
;
Female
;
Breast Neoplasms/mortality*
;
Middle Aged
;
Trastuzumab/adverse effects*
;
Aged
;
Adult
;
Singapore/epidemiology*
;
Antineoplastic Agents, Immunological/adverse effects*
;
Camptothecin/adverse effects*
;
Immunoconjugates/adverse effects*
;
Retrospective Studies
;
Progression-Free Survival
;
Receptor, ErbB-2/metabolism*
;
Neoplasm Metastasis
;
Dose-Response Relationship, Drug
;
Treatment Outcome
;
Registries
2.Exploration of differences in decoction phase state, material form, and crystal form between Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O based on supramolecules of traditional Chinese medicine.
Yao-Zhi ZHANG ; Wen-Min PI ; Xin-Ru TAN ; Ran XU ; Xu WANG ; Ming-Yang XU ; Xue-Mei HUANG ; Peng-Long WANG
China Journal of Chinese Materia Medica 2025;50(2):412-421
With Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum drug pair as the research object, supramolecular chemistry of traditional Chinese medicine(TCM) was used to study differences between the compatibility of herbal medicine Glycyrrhizae Radix et Rhizoma with mineral medicine Gypsum Fibrosum and its main component CaSO_4·2H_2O, so as to preliminarily discuss the scientific connotation of compatibility of Gypsum Fibrosum in clinical application. A Malvern particle sizer, a scanning electron microscope(SEM), and a conductivity meter were used to observe and determine the physical properties such as microscopic morphology, particle size, and conductivity of Gypsum Fibrosum, CaSO_4·2H_2O, and water decoctions of them with Glycyrrhizae Radix et Rhizoma. An inductively coupled plasma optical emission spectrometer(ICP-OES) was employed to detect the inorganic metal elements in Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Isothermal titration calorimetry(ITC) was conducted to quantify the interactions of Gypsum Fibrosum and CaSO_4·2H_2O with Glycyrrhizae Radix et Rhizoma. A Fourier transform infrared spectrometer(FTIR) was used to analyze the characteristic absorption peak change of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. X-ray diffraction(XRD) was performed to determine the crystal structure and phase composition of Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum and Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O. Further, glycyrrhizic acid(GA) was substituted for Glycyrrhizae Radix et Rhizoma to co-decoct with Gypsum Fibrosum, CaSO_4·2H_2O, and freeze-dried powder of their respective water decoctions. The results of XRD were used for verification analysis. The results showed that although CaSO_4·2H_2O is the main component of Gypsum Fibrosum, there were significant differences between their decoctions and between the decoctions of them with Glycyrrhizae Radix et Rhizoma. Specifically,(1) Both CaSO_4·2H_2O and Gypsum Fibrosum were amorphous fibrous. However, the particle size and conductivity were significantly different between the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(2) Under SEM, Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O was a hybrid system with various morphologies, while Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum presented uniform nanoparticles.(3) The particle sizes and conductivities of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum were significantly different and did not follow the same tendency as those of the decoctions of CaSO_4·2H_2O and Gypsum Fibrosum alone.(4) Compared with Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O, Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum had stronger molecular binding ability and functional group structure change.(5) The crystal form was largely different between the freeze-dried powder of CaSO_4·2H_2O decoction and Gypsum Fibrosum decoction, and their crystal forms were also significantly different from those of the freeze-dried powder of Glycyrrhizae Radix et Rhizoma-CaSO_4·2H_2O and Glycyrrhizae Radix et Rhizoma-Gypsum Fibrosum decoctions. The reason for the series of differences is that Gypsum Fibrosum is richer in trace elements than CaSO_4·2H_2O. The XRD results of GA-Gypsum Fibrosum and GA-CaSO_4·2H_2O decoctions further prove the importance of trace elements in Gypsum Fibrosum for supramolecule formation. This research preliminarily reveals the influence of compatibility of Gypsum Fibrosum or CaSO_4·2H_2O on decoction phase state, material form, and crystal form, providing a basis for the rational clinical application of Gypsum Fibrosum.
Drugs, Chinese Herbal/chemistry*
;
Calcium Sulfate/chemistry*
;
Glycyrrhiza/chemistry*
;
Crystallization
;
Particle Size
;
Medicine, Chinese Traditional
;
Rhizome/chemistry*
3.Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.
Lin-Zi LONG ; Ling TAN ; Feng-Qin XU ; Wen-Wen YANG ; Hong-Zheng LI ; Jian-Gang LIU ; Ke WANG ; Zhi-Ru ZHAO ; Yue-Qi WANG ; Chao-Ju WANG ; Yi-Chao WEN ; Ming-Yan HUANG ; Hua QU ; Chang-Geng FU ; Ke-Ji CHEN
Chinese journal of integrative medicine 2025;31(5):402-411
OBJECTIVE:
To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved.
METHODS:
Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively.
RESULTS:
The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01).
CONCLUSIONS
Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals
;
Drugs, Chinese Herbal/therapeutic use*
;
Hypertension/pathology*
;
Renin-Angiotensin System/drug effects*
;
Rats, Inbred SHR
;
Oxidative Stress/drug effects*
;
Male
;
Rats, Inbred WKY
;
Blood Pressure/drug effects*
;
Myocardium/pathology*
;
Rats
;
Inflammation/pathology*
4.Robotic visualization system-assisted microsurgical reconstruction of the reproductive tract in male rats
Zheng LI ; Jian-Jun DONG ; Ming LIU ; Xun-Zhu WU ; Ren-Feng JIA ; San-Wei GUO ; Kai MENG ; Chen-Cheng YAO ; Er-Lei ZHI ; Gang LIU ; Da-Xian TAN ; Zheng LI ; Peng LI
National Journal of Andrology 2024;30(8):675-680
Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100%in both groups,and that of anastomosis leakage after VE was 16.7%in the experimental group and 14.3%in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P<0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P<0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P<0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.
5.Arthroscopic surgery for injuries to the popliteal tendon area of the lateral meniscus
Ming-Tao ZHANG ; Zhi-Tao YANG ; Tao LIU ; Bo-Rong ZHANG ; Xiao-Yi TAN ; Jin JIANG ; Li-Ping AN ; Xiang-Dong YUN
China Journal of Orthopaedics and Traumatology 2024;37(7):713-717
Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P<0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P<0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7%(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.
6.Study on the clinical effect of meridian massage in the treatment of lumbar disc herniation
Sheng-Hua HE ; Huang-Sheng TAN ; Yong HUANG ; Hua-Long FENG ; Zhi-Ming LAN ; Yuan-Fei FU ; Yong JIANG ; Ju-Yi LAI
China Journal of Orthopaedics and Traumatology 2024;37(10):991-996
Objective To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH).Methods Between July 2020 and April 2023,82 patients with lumbar disc herniation were selected,including 58 males and 24 females,aged from 23 to 55 years old with an average of(43.76±6.64)years old.According to the different treatment methods,they were divided into observation group and control group with 41 cases in each group.The control group was treated with routine treatment,and the observation group was treated with meridian massage on the basis of routine treatment.In the control group,there were 30 males and 11 females;aged from 22 to 52 years old with an average of(42.27±9.34)years old;the Body mass index(BMI)ranged from 19 to 28 kg·m-2 with an average of(23.82±1.08)kg·m-2;the course of disease ranged from 0.5 to 3.0 years(2.40±0.48)years.There were 28 cases in L4,5 segment and 13 cases in L5S1 segment.In the observation group,there were 28 males and 13 females;the age ranged from 19 to 54 years old(42.19±9.26)years old;the BMI ranged from 18 to 29 kg·m-2 with an average of(23.73±1.15)kg·m-2;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45)years;there were 26 cases in L4,5 segment and 15 cases in L5S1 segment.Visual analogue scale(VAS),Oswestry disability index(ODI),M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment,and the clinical efficacy was evaluated by the standard of curative effect evaluation.Results After treatment,VAS[(3.24±1.45)vs(4.46±0.64)],ODI[(11.45±1.98)%vs(17.21±2.74)%]and TCM symptom score[(2.03±0.27)vs(3.99±0.54)]of the observation group were lower than those of the control group.The score of M-JOA[(23.43±2.61)vs(19.37±1.62)]increased(P<0.05).The scores of VAS,ODI andTCM symptoms in the observation group were lower than those in the control group,while the scores of M-JOA were higher than those in the control group(P<0.05).Conclusion Meridian massage is effective in the treatment of LDH,which can effectivelyrelieve low back pain,improve clinical symptoms and increaselumbar function,which is worthy of clinical promotion.
8.Biomechanical analysis of four internal fixations for Pauwels Ⅲ femoral neck fractures with defects.
Zhi-Hao SU ; Hong-Li TAN ; Zi-Huan XU ; Peng-Fei LI ; Yong-Qin WANG ; Shuang LI ; Ming NI
China Journal of Orthopaedics and Traumatology 2023;36(3):255-261
OBJECTIVE:
To investigate the biomechanical characteristics of different internal fixations for Pauwels type Ⅲ femoral neck fracture with defect, and provide reference for the treatment of femoral neck fracture.
METHODS:
Three-dimensional (3D) finite element models of femoral neck fractures were established based on CT images, including fracture and fracture with defects. Four internal fixations were simulated, namely, inverted cannulated screw(ICS), ICS combined with medial buttress plate, the femoral neck system (FNS) and FNS combined with medial buttress plate. The von Mises stress, model stiffness and fracture displacements of fracture models under 2 100 N axial loads were measured and compared.
RESULTS:
When femoral neck fracture was fixed by ICS and FNS, the peak stress was mainly concentrated on the surface of the screw near the fracture line, and the peak stress of FNS is higher than that of ICS;When the medial buttress plate was combined, the peak stress was increased and transferred to medial buttress plate, with more obvious of ICS fixation. For the same fracture model, the stiffness of FNS was higher than that of ICS. Compared with femoral neck fracture with defects, fracture model showed higher stiffness in the same internal fixation. The use of medial buttress plate increased model stiffness, but ICS increased more than FNS. The fracture displacement of ICS model exceeded that of FNS.
CONCLUSION
For Pauwels type Ⅲ femoral neck fracture with defects, FNS had better biomechanical properties than ICS. ICS combined with medial buttress plate can better enhance fixation stability and non-locking plate is recommended. FNS had the capability of shear resistance and needn't combine with medial buttress plate.
Humans
;
Femoral Neck Fractures/surgery*
;
Fracture Fixation, Internal/methods*
;
Bone Screws
;
Bone Plates
;
Biomechanical Phenomena
;
Finite Element Analysis
9.A case of low-grade fibromyxoid sarcoma of the temporal bone.
Ming Yang MAO ; Guo Dong FENG ; Yu CHEN ; Xiao Hua SHI ; Xu TIAN ; Tong SU ; Hui Ying SUN ; Zhen Tan XU ; Wen Sheng REN ; Zhu Hua ZHANG ; Zhi Qiang GAO ; Zheng Yu JIN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(1):64-67
10.Robot-assisted PVP for the treatment of osteoporotic fractures of the upper thoracic vertebra.
Ju-Yi LAI ; Huang-Sheng TAN ; Hua-Long FENG ; Zhi-Ming LAN ; Zhi-Tao SUN ; Ye-Guang WANG ; Jian WANG ; Yuan-Fei FU ; Shen-Ghua HE
China Journal of Orthopaedics and Traumatology 2023;36(9):859-865
OBJECTIVE:
To investigate the clinical effect of "Tianji" orthopedic robot-assisted percutaneous vertebro plasty(PVP) surgery in the treatment of upper thoracic osteoporotic fracture.
METHODS:
A retrospective analysis was performed on 32 patients with upper thoracic osteoporotic fracture who underwent PVP surgery in Shenzhen Hospital of Traditional Chinese Medicine from August 2016 to June 2022. There were 8 males and 24 females, ranging in age from 58 to 90 years old, with a mean of (67.75±12.27) years old. Fifteen patients were treated with robot-assisted PVP surgery (robot group), including 3 males and 12 females, with an average age of (68.5±10.3) years. Fracture location:1 case of T2 fracture, 1 case of T3 fracture, 3 cases of T4 fracture, 3 cases of T5 fracture, and 7 cases of T6 fracture. The follow-up period ranged from 1.0 to 3.0 months, with a mean of (1.6±0.7) months. Seventeen patients underwent routine PVP surgery (conventional group), including 5 males and 12 females, with an average age of (66.8±11.6) years old. Fracture location:1 case of T1 fracture, 5 cases of T4 fracture, 2 cases of T5 fracture and 9 cases of T6 fracture. The follow-up period ranged from 0.5 to 4.0 months, with a mean of (1.5±0.6) months. Preoperative and postoperative visual analogue scale(VAS) and Oswestry disability index(ODI) scores were compared between the two groups, and the number of punctures, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage, and intraoperative radiation dose were compared between the two groups.
RESULTS:
Number of punctures times, perspective times, operation time, intraoperative blood loss, bone cement distribution, bone cement leakage and intraoperative radiation dose in the robot group were all significantly better than those in the conventional group(P<0.05). VAS of 2.03±0.05 and ODI of (22.16±4.03) % in the robot group were significantly better than those of the robot group before surgery, which were (8.67±0.25) score and (79.40±7.72)%(t=100.869, P<0.001;t=25.456, P<0.001). VAS of 2.17±0.13 and ODI of (23.88±6.15)% in the conventional group were significantly better than those before surgery, which were (8.73±0.18) score and (80.01±7.59)%(t=121.816, P<0.001;t=23.691, P<0.001). There was no significant difference in VAS and ODI between the two groups after operation (t=-3.917, P=0.476;t=-0.922, P=0.364).
CONCLUSION
Robot-assisted PVP in the treatment of upper thoracic osteoporotic fractures can further improve surgical safety, reduce bone cement leakage, and achieve satisfactory clinical efficacy.
Female
;
Male
;
Humans
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Osteoporotic Fractures/surgery*
;
Robotics
;
Blood Loss, Surgical
;
Bone Cements
;
Retrospective Studies
;
Thoracic Vertebrae/surgery*

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