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 investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI).Methods:This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results:The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2( t=9.482, P<0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1( t=-13.132, P<0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 ( t=-12.510, P<0.01). There was no complication such as recurred instability or joint stiffness. Conclusions:Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

Objective:To investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI).Methods:This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results:The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2( t=9.482, P<0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1( t=-13.132, P<0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 ( t=-12.510, P<0.01). There was no complication such as recurred instability or joint stiffness. Conclusions:Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

Objective:To investigate the correlation between plasma fibrinogen/serum albumin ratio (FAR) and the degree of cerebral artery stenosis in patients with acute cerebral infarction (ACI).Methods:Clinical data of 189 patients with acute cerebral infarction diagnosed and treated in the Department of Neurology of the First Affiliated Hospital of Hainan Medical College from January 2021 to March 2023 were selected for retrospective analysis. Digital subtraction angiography (DSA) was improved, and they were divided into four groups according to the degree of intracranial vascular stenosis according to NASCET grading method: no stenosis group (47 cases), mild stenosis group (45 cases), moderate stenosis group (39 cases) and severe stenosis and occlusion group (58 cases). The differences of basic data, plasma fibrinogen/serum albumin ratio (FAR) and other inflammatory indicators among all groups were compared, and the correlation between FAR level and the severity of cerebral artery stenosis was analyzed. Multivariate Logistic regression was used to explore the factors influencing to cerebral artery stenosis and ROC curve was used to evaluate the diagnostic value of FAR in the degree of cerebral artery stenosis in cerebral infarction patients.Results:There were significant differences in blood neutrophil (NEU), mean platelet volume (MPV), fibrinogen (FIB), fibrinogen (FIB), albumin (ALB) and FAR among the 4 groups (statistical values were H=11.50, H=8.44, F=5.16, H=30.93, H=40.38; all P<0.05). Correlation analysis showed a positive correlation between FAR and the degree of cerebral artery stenosis ( r=0.455, P<0.05). Multivariate Logistic regression showed that FAR was an independent risk factor for the degree of cerebral artery stenosis ( OR=1.445, 95% CI=1.261-1.655, P<0.001). Conclusion:FAR is an independent risk factor for cerebral artery stenosis in patients with acute cerebral infarction (ACI), and may be a new biomarker for predicting cerebral artery stenosis.

Based on the discussions in the The Inner Canon of Yellow Emperor （《黄帝内经》）， it is proposed that in the course of the disease， "bind" represents the initial stage of pulmonary nodules， while "accumulation" represents the final form. In terms of the pathogenesis， "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules， while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang （少阳） or shaoyin （少阴）， resulting in a complex of cold and heat， and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore， the treatment principle should be to regulate the cardinal mechanism， dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat， it is suggested to use Chaihu Guizhi Decoction （柴胡桂枝汤）， Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）， or Chaihu Xianxiong Decoction （柴胡陷胸汤） for disturbance of shaoyang pivot， while for shaoyin pivot dysfunction， modified Mahuang Fuzi Xixin Decoction （麻黄附子细辛汤） or Shengjiang Powder （升降散） can be used.

Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To describe the detail sampling design,weighting,instruments,filed procedures and quality control methods of the epidemiological survey on dementia among community residents in Tongliao City.Methods:A three-stage disproportionate probability sampling design was used to investigate the inhabitants aged 65 years and over in Tongliao City,Inner Mongolia Autonomous Region.The 10/66 Dementia Research Group(10/66 DRG)assessment instruments were used to diagnose dementia,using computer-assisted personal interview mode in the selected older people.Comprehensive quality control methods were implemented throughout the field-work.Results:A total of 166 villages or communities were sampled from nine counties or districts in Tongliao Cit-y.Totally 4 345 older people were interviewed with 96.2％response rate.By calculating sampling design weights,non-response adjustment weights and post-stratification adjustment weights,these weights were multiplied and per-formed trimming adjustment and standardization adjustment to generate final weights.The 171 interviewers were well-trained and qualified to carry out filed interview.Quality control methods included computer data check,audio record check,and telephone check in order to ensure the quality of the survey.Conclusion:This survey is imple-mented using a rigorous sampling design and timely quality control methods,and uses the 10/66 DRG assessment instruments with satisfactory international validity and reliability as survey instruments,which has international cross-cultural comparability.It provides a valid and feasible methodology of epidemiological survey on dementia for further studies in different regions in China.

Surgical resection and radiotherapy have been commonly applied to the treatment of early- and intermediate-stage Merkel cell carcinoma. In recent years, immunotherapy based on immunogenic characteristics of Merkel cell carcinoma has been proved to be effective in the treatment of advanced Merkel cell carcinoma. This review focuses on advances in the treatment of Merkel cell carcinoma, and provides a reference for its clinical diagnosis and treatment.

[Objective]To investigate the effect and mechanism of Soufeng Jiedu Decoction on cisplatin-induced acute kidney injury.[Methods]Forty C57BL/6J mice were randomly divided into 5 groups,8 mice in each group:control group and model group were gavaged with distilled water,positive control group was gavaged with prednisolone 5 mg/(kg·d),Soufeng Jiedu Decoction low and high dose groups were gavaged with Soufeng Jiedu Decoction 300 and 500 mg/(kg·d)respectively.These drugs were administered continuously for 10 days.On the 7th day of administration,mice in model group,positive control group,Soufeng Jiedu Decoction low dose group,and Soufeng Jiedu Decoction high dose group were intraperitoneally injected with 20 mg·kg-1 cisplatin,while the control group received an equivalent volume of 0.9%sodium chloride solution.Biochemical approaches were utilized to measure the levels of blood urea nitrogen(BUN),serum creatinine(SCr),malondialdehyde(MDA),and the activity of superoxide dismutase(SOD)and catalase(CAT).Kidney tissue pathological morphology was assessed using hematoxylin-eosin(HE)staining in all groups.Real time-quantitative polymerase chain reaction(RT-qPCR)was employed to determine the gene expressions of kidney injury molecule-1(Kim-1),neutrophil gelatinase-associated lipocalin(Ngal),quinone oxidoreductase 1(Nqo1)and glutamate cysteine ligase(Gclm)in the kidney of mice.Western blot analysis was conducted to evaluate the protein expressions of nuclear factor erythroid 2-related factor 2(NRF2),heme oxygenase-1(HO-1),p62,microtubule-associated protein light chain 3(LC3B)and phosphorylated-AMP-activated protein kinase(p-AMPK).[Results]Compared with control group,model group exhibited a significant increase in levels of BUN and SCr,as well as upregulation of Kim-1 and Ngal gene expression(P<0.01).Notably,severe kidney injury was observed in model group,characterized by tubular degeneration,edema,necrosis,cystic dilatation with focal hemorrhage.Moreover,model group exhibited a significant increase in MDA levels,accompanied by a notable decrease in CAT and SOD activities(P<0.01).On the other hand,model group displayed elevated expressions of renal Nqo1 and Gclm genes,as well as increased protein expressions of NRF2,HO-1,and LC3B,while the protein expressions of p62 and p-AMPK were significantly reduced(P<0.01).Compared with model group,treatment with Soufeng Jiedu Decoction resulted in a significant reduction in BUN and SCr levels,as well as suppression of Kim-1 and Ngal gene expression in the kidney of mice.Furthermore,Soufeng Jiedu Decoction ameliorated acute kidney injury-associated renal tissue lesions.Treatment with Soufeng Jiedu Decoction also led to a decrease in MDA levels,and an increase in CAT and SOD activities within the kidney.Additionally,Soufeng Jiedu Decoction promoted the expression of Nqo1 and Gclm genes,as well as the protein expressions of NRF2,HO-1,LC3B and p-AMPK,while inhibiting the expression of p62 protein(P<0.01).[Conclusion]Soufeng Jiedu Decoction effectively alleviates cisplatin-induced acute kidney injury possibly by inhibiting oxidative stress and promoting autophagy in the kidney.