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

This review summarizes recent clinical progress in the field of lung cancer within the multidisciplinary team(MDT)diagnosis and treatment model across domestic and international studies.In the perioperative treatment of early-stage resectable non-small-cell lung cancer(NSCLC),the"sandwich"strategy combining preoperative neoadjuvant therapy with postoperative adjuvant therapy has demonstrat-ed significant survival benefits for patients.Notably,domestic toripalimab combined chemotherapy significantly increases the major patho-logic response(MPR)rate and event-free survival(EFS)rate of resectable stage Ⅲ NSCLC patients,emerging as a novel treatment regimen for perioperative NSCLC.For unresctable NSCLC patients,consolidative therapy combined with osimertinib,a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor,following radical chemotherapy has significantly extended progression free survival,filling the gap in targeted therapy for stage Ⅲ lung cancer.Furthermore,the combination of immunotherapy and anti-angiogenic agents has ef-fectively improved the overall survival of advanced NSCLC patients.Significant progress has also been made in the field of antibody-drug conjugates,with agents such as sacituzumab and trastuzumab demonstrating substantial therapeutic efficacy.In the field of extensive-stage small-cell lung cancer(ES-SCLC),the bispecific antibody tarlatamab targeting Delta-like ligand 3(DLL3)and cluster of differentiation 3(CD3)has exhibited significant efficacy,and has received accelerated approval from U.S.Food and Drug Administration(FDA)as a sec-ond-line treatment for ES-SCLC.

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

Investigating the correlation between micronucleus formation and male infertility has the potential to improve clinical diagnosis and deepen our understanding of pathological progression. Our study enrolled 2252 male patients whose semen was analyzed from March 2023 to July 2023. Their clinical data, including semen parameters and age, were also collected. Genetic analysis was used to determine whether the sex chromosome involved in male infertility was abnormal (including the increase, deletion, and translocation of the X and Y chromosomes), and subsequent semen analysis was conducted for clinical grouping purposes. The participants were categorized into five groups: normozoospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, and azoospermia. Patients were randomly selected for further study; 41 patients with normozoospermia were included in the control group and 117 patients with non-normozoospermia were included in the study group according to the proportions of all enrolled patients. Cytokinesis-block micronucleus (CBMN) screening was conducted through peripheral blood. Statistical analysis was used to determine the differences in micronuclei (MNi) among the groups and the relationships between MNi and clinical data. There was a significant increase in MNi in infertile men, including those with azoospermia, compared with normozoospermic patients, but there was no significant difference between the genetic and nongenetic groups in azoospermic men. The presence of MNi was associated with sperm concentration, progressive sperm motility, immotile spermatozoa, malformed spermatozoa, total sperm count, and total sperm motility. This study underscores the potential utility of MNi as a diagnostic tool and highlights the need for further research to elucidate the underlying mechanisms of male infertility.
Humans ; Male ; Infertility, Male/genetics* ; Adult ; Micronucleus Tests ; Semen Analysis ; Oligospermia/genetics* ; Azoospermia/genetics* ; Chromosome Aberrations ; Sperm Count ; Micronuclei, Chromosome-Defective ; Middle Aged

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.

Objective To investigate the protective effect of mitochondrial division inhibitor 1(Mdivi-1),a mitophagy inhibitor,on cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.Methods A total of 72 neonatal SD rats(half male and half female,aged 7 d,weighing 16.14±3.08 g)were randomly divided into 4 groups(n=18):blank control group(CON),Mdivi-1+blank control group(MCON),propofol+hypoxia group(PH),and Mdivi-1+propofol+hypoxia group(MPH).The MCON group and MPH group were pretreated with 2.4 mg/kg Mdivi-1 in 30 min in advance,and subsequently,50 mg/kg propofol was respectively given to the PH group and the MPH group.Immediately after the intraperitoneal injections were completed,the corresponding rats were transferred into a constant temperature chamber containing 18%O2.Then the rats were continuously monitored until resuming the reversing reflex and then transferred to a normoxic environment.The hypoxic treatment was carried out once per day for 7 consecutive days.Transcriptome sequencing was used to screen for differential expressed genes(DEGs),and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis was employed to conduct functional analysis.Morris water maze test was applied to exam spatial learning and memory abilities.HE staining was used to observe the morphological changes of neurons in the hippocampal CA1 region.Morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy(TEM).Western blotting was utilized to detect the expression of Parkin Rbr E3 ubiquitin protein ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)in the hippocampal tissues.Results KEGG analysis results indicated that the mitophagy pathway was more significantly enriched in the PH group when compared with the CON group.Morris water maze test revealed that the PH group exhibited obviously prolonged escape latency(P<0.05),reduced frequency of crossing the platform(P<0.05),and shortened residence time in the target quadrant(P<0.01)when compared with the CON group and the MPH group.HE staining demonstrated that the cells in the PH group were in disordered arrangement,with great loss in cell count in some areas,and widened intercellular spaces.Although the cell arrangement in the MPH group also showed a sparse state,but the condition was milder than that in the PH group,with slightly widened intercellular space.In the CON group and the MCON group,the cells exhibited round in shape,good morphological structure,relatively clear contours,and uniform cell nuclei.TEM revealed that in the hippocampal neurons of the PH group,the mitochondria were swollen and deformed,and mitochondrial cristae were disordered,dissolved and disappeared.In the MPH group,only some mitochondria were swollen and the cristae were reduced.However,the mitochondrial morphology of the CON and MCON groups was relatively complete,and the matrix was uniform.Western blot analysis showed that the expression levels of Parkin and PINK1 in the hippocampus were up-regulated in the PH group than the CON group(P<0.05),and reduced in the MPH group than the PH group(P<0.05).Conclusion Mdivi-1 may reduce hippocampal neuron damage by inhibiting excessive mitophagy and then improve cognitive dysfunction in immature SD rats induced by hypoxia combined with propofol.

An integrated extraction-purification process was established in this work for efficient phycocyanin production from dried Spirulina platensispowder.Initially,phycocyanin was extracted from algal biomass using a combined swelling-enzymatic lysis strategy.Single-factor experiments were carried out to systematically evaluate the effects of critical parameters,including system pH,enzymatic hydrolysis duration,and temperature,on phycocyanin extraction yield.Subsequently,a three-factor,three-level Box-Behnken response surface methodology design was employed to optimize the extraction process,with phycocyanin concentration and purity in the extract serving as response variables.A predictive regression model identified optimal conditions as follows:pH 6.4,hydrolysis time 3.2 h,and temperature 35.4℃.Experimental validation under these conditions yielded a phycocyanin recovery of 26.6%.Following extraction,purification was achieved via a polyethylene glycol-phosphate aqueous two-phase extraction system,which elevated the final purity to 4.21.Results demonstrated that the swelling-enzymatic lysis approach effectively disrupted algal cellular structures,significantly enhancing phycocyanin release efficiency.Concurrently,the aqueous two-phase system enabled selective partitioning and enrichment of the target protein under mild conditions.The integrated process exhibited high extraction efficiency,gentle purification,and robust operability,rendering it suitable for the scalable production of natural phycocyanin.This work provided both methodological foundations and technical support for advancing phycocyanin applications in natural pigments,biomedicine,and analytical detection.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

This review summarizes recent clinical progress in the field of lung cancer within the multidisciplinary team(MDT)diagnosis and treatment model across domestic and international studies.In the perioperative treatment of early-stage resectable non-small-cell lung cancer(NSCLC),the"sandwich"strategy combining preoperative neoadjuvant therapy with postoperative adjuvant therapy has demonstrat-ed significant survival benefits for patients.Notably,domestic toripalimab combined chemotherapy significantly increases the major patho-logic response(MPR)rate and event-free survival(EFS)rate of resectable stage Ⅲ NSCLC patients,emerging as a novel treatment regimen for perioperative NSCLC.For unresctable NSCLC patients,consolidative therapy combined with osimertinib,a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor,following radical chemotherapy has significantly extended progression free survival,filling the gap in targeted therapy for stage Ⅲ lung cancer.Furthermore,the combination of immunotherapy and anti-angiogenic agents has ef-fectively improved the overall survival of advanced NSCLC patients.Significant progress has also been made in the field of antibody-drug conjugates,with agents such as sacituzumab and trastuzumab demonstrating substantial therapeutic efficacy.In the field of extensive-stage small-cell lung cancer(ES-SCLC),the bispecific antibody tarlatamab targeting Delta-like ligand 3(DLL3)and cluster of differentiation 3(CD3)has exhibited significant efficacy,and has received accelerated approval from U.S.Food and Drug Administration(FDA)as a sec-ond-line treatment for ES-SCLC.