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

OBJECTIVE: To evaluate the early effectiveness of navigation-free robot-assisted total knee arthroplasty (TKA) compared to traditional TKA in the treatment of knee osteoarthritis combined with extra-articular deformities. METHODS: The clinical data of 30 patients with knee osteoarthritis combined with extra-articular deformities who met the selection criteria between June 2019 and January 2024 were retrospectively analyzed. Fifteen patients underwent CORI navigation-free robot-assisted TKA and intra-articular osteotomy (robot group) and 15 patients underwent traditional TKA and intra-articular osteotomy (traditional group). There was no significant difference in age, gender, body mass index, affected knee side, extra-articular deformity angle, deformity position, deformity type, and preoperative knee range of motion, American Knee Society (KSS) knee score and KSS function score, and lower limb alignment deviation between the two groups ( P>0.05). The operation time, intraoperative blood loss, and complications of the two groups were recorded and compared. The knee range of motion and lower limb alignment deviation were recorded before operation and at 6 months after operation, and the knee joint function was evaluated by KSS knee score and function score. RESULTS: There was no significant difference in operation time between the two groups ( P>0.05); the intraoperative blood loss in the robot group was significantly less than that in the traditional group ( P<0.05). Patients in both groups were followed up 6-12 months, with an average of 8.7 months. The incisions of all patients healed well, and there was no postoperative complication such as thrombosis or infection. At 6 months after operation, X-ray examination showed that the position of the prosthesis was good in both groups, and there was no loosening or dislocation of the prosthesis. The knee joint range of motion, the lower limb alignment deviation, and the KSS knee score and KSS function score significantly improved in both groups ( P<0.05) compared to preoperative ones. The changes of lower limb alignment deviation and KSS function score between pre- and post-operation in the robot group were significantly better than those in the traditional group ( P<0.05), while the changes of other indicators between pre- and post-operation in the two groups were not significant ( P>0.05). CONCLUSION Compared to traditional TKA, navigation-free robot-assisted TKA for knee osteoarthritis with extra-articular deformities results in less intraoperative blood loss, more precise reconstruction of lower limb alignment, and better early effectiveness. However, long-term effectiveness require further investigation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Robotic Surgical Procedures/methods* ; Male ; Female ; Retrospective Studies ; Range of Motion, Articular ; Middle Aged ; Aged ; Treatment Outcome ; Osteotomy/methods* ; Knee Joint/physiopathology* ; Operative Time

Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts ( n = 101) and those with low sperm motility or concentration ( n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 ( MAP2K2 ), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.
Male ; Humans ; Spermatozoa/metabolism* ; RNA, Transfer/genetics* ; Sperm Motility/genetics* ; Adult ; Semen Analysis ; Sexual Abstinence/physiology* ; Sperm Count ; DNA Fragmentation

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To explore the effect of seminar based on case-based learning(CBL)in practical teaching of physical therapy. Methods From July,2021 to June,2022,42 rehabilitation therapy students for internships in Rehabilitation Medicine Center,the First Affiliated Hospital of Nanjing Medical University were non-directionally recruited,and random-ly divided into control group(n = 21)and experimental group(n = 21).The experimental group received instruc-tion using seminar and CBL,while the control group received CBL alone,for three months.The scores of theoret-ical and practical assessments were observed,and the satisfaction was investigated using a self-designed question-naire. Results The scores of both theoretical and practical assessments were better in the experimental group than in the control group(t>2.421,P<0.05);while the satisfaction was better in terms of motivating learning enthusiasm,enhanc-ing learning abilities,cultivating clinical reasoning skills,improving teacher-student communication,promoting teamwork,enhancing overall competence,and satisfying to the teaching in the experimental group than in the control group(χ2>6.667,P<0.05). Conclusion The combination of seminar with CBL would enhance the effect of practical teaching in physical therapy.

Drug nanocrystals self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. There are more and more researches on DNSPE in the field of drug delivery in recent years. On the basis of summarizing the research status of DNSPE used as drug delivery systems, this paper comprehensively reviewed the research progress of three key issues, such as the main factors affecting construction of DNSPE, characterization methods of properties and structures, and in vivo fate, and looked forward to the industrialization prospect, which is beneficial to deepen the comprehensive research of DNSPE and promote its application in the field of drug delivery.

Objective To explore clinical effect of single small incision with honeycomb titanium plate in treating acute acromioclavicular dislocation.Methods The clinical data of 40 patients with acute acromioclavicular dislocation admitted from December 2019 to December 2021 were retrospectively analyzed and divided into two groups according to different surgical methods.Among them,20 patients were fixed with single small incision with honeycomb titanium plate(titanium plate group),including 11 males and 9 females,aged from 23 to 65 years old with an average of(47.40±12.58)years old;12 patients on the left side,8 patients on the right side;11 patients with type Ⅲ,3 patients with type Ⅳ,and 6 patients with type Ⅴ according to Rockwood classification.Twenty patients were fixed with clavicular hook plate(clavicular hook group),including 8 males and 12 females,aged from 24 to 65 years old with an average of(48.40±12.08)years old;12 patients on the left side,8 patients on the right side;10 patients with type Ⅲ,2 patients with type Ⅳ,and 8 patients with type V according to Rockwood classifica-tion.Operative time,incision length,intraoperative blood loss,hospital stay,visual analogue scale(VAS)and Constant-Murley score of shoulder joint function were compared between two groups.Anteroposterior radiographs of the affected shoulder joint were recorded before,immediately and 6 months after surgery,and the coracoclavicular distance was measured and compared.Results Both groups of patients were successfully completed operation without serious complications.All patients were fol-lowed up for 6 to 15 months with an average of(11.9±4.8)months.There were no incisional infection,internal plant fracture or failure,bone tunnel fracture and other complications occurred.The incision length of titanium plate group(35.90±3.14)mm was significantly shorter than that of clavicular hook group(49.30±3.79)mm(P＜0.05).There were no significant difference in operative time,intraoperative blood loss and hospital stay between two groups(P＞0.05).At 1 and 3 months after operation,VAS of titanium plate group was lower than that of clavicular hook group(P＜0.05).Connstant-Murley scores in titanium plate group at 1,3 and 6 months after operation were(86.80±1.36),(91.60±2.32)and(94.90±2.22),respectively;and in clavicular hook group were(78.45±5.47),(85.55±2.01)and(90.25±1.92),which were higher than that of clavicular hook group(P＜0.05).There was no significant difference in coracoclavicular distance between two groups immediately and 6 months after op-eration(P＞0.05).Conclusion For the treatment of acute acromioclavicular joint dislocation,single small incision combined with honeycomb titanium plate have advantages of shorter incision,fast recovery of shoulder joint function without the second operation,and has good satisfaction of patient.

The steps for installation and withdrawal of WYD2000 field surgical lamp were introduced.The failures and causes of broken cross-arm connector of WYD2000 field surgical lamp were analyzed.The problems of WYD2000 field surgical lamp in vulnerability to breaking and difficulty in maintenance were solved by designing and manufacturing a special maintenance tool and optimizing the materials and fixing mode of cross-arm connection.References were provided for main-tenance and improvement of WYD2000 field surgical lamp.[Chinese Medical Equipment Journal,2024,45(4):116-118]