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 examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 μg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 μg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.
Mice ; Animals ; NF-kappa B/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Glycosides/pharmacology* ; Cholesterol, LDL ; Atherosclerosis/genetics* ; Signal Transduction ; Inflammation/drug therapy* ; Interleukin-6 ; Apolipoproteins E/pharmacology* ; RNA, Messenger/metabolism*

OBJECTIVE: To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H METHODS: Sprague-Dawley rats were exposed to H RESULTS: The morphological investigation showed that XBJ attenuated H CONCLUSIONS XBJ ameliorated H
Animals ; Claudin-5 ; Drugs, Chinese Herbal ; Endothelial Cells ; Hydrogen Sulfide ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome/drug therapy*

IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition of autoimmune etiology in recent twenty years, mainly manifesting as mass-forming lesions in single or multiple organs. In the past, it was often missed or misdiagnosed as inflammation or tumor. Patients may die from multiple organ failure due to end-stage fibrosis if they are not treated promptly. However, the number of clinically confirmed cases has gradually increased with the improvement of diagnostic level in recent years, and these patients have benefited greatly after receiving early treatment. Although patients generally respond well to traditional immunosuppressors including glucocorticoids and disease-modifying anti-rheumatic drugs, refractory and recurrent cases, even patients with glucocorticoid contraindication are common. Important mechanistic insights have been derived from studies of B-cell depletion therapy, but greater awareness of the pathophysiology of IgG4-RD is still badly needed to identify novel therapeutic targets. In this article, we reviewed the pathogenesis progress and promising therapy of IgG4-RD to seek better clinical management of IgG4-RD.

Objective:To explore the feasibility, safety and effectiveness of anatomical partial lobectomy.Methods:The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules.Results:A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation.Conclusion:Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

Objective:To explore the feasibility, safety and effectiveness of anatomical partial lobectomy.Methods:The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules.Results:A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation.Conclusion:Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

ObjectiveThe present study was designed to explore the role of high glucose and macrophage polarization and their potential relation to septic intestinal injury. MethodsBKS-DB （Lepr ko/ko） and BKS-DB （Lepr wt/wt） male mice were randomly divided into 4 groups （n=6）， which include non-diabetic mice sham group （NDMS group）， non-diabetic mice CLP group （NDMCLP group）， diabetic mice sham group （DMS group）， diabetic mice CLP group （DMCLP group）. The cell experiment was divided into four groups： control group （Sham group）， high glucose group （HG group）， lipopolysaccharide group （LPS group）， high glucose and lipopolysaccharide group （HG+LPS group）. Animal and cell models were respectively established by cecal ligation and puncture （CLP） and co-stimulation of high glucose and LPS. The pathological injury and Occludin and ZO-1 protein expression of intestinal tissue were detected. The distribution and polarization characteristics of macrophages were detected by immunofluorescence， real-time quantitative PCR （RT-PCR） and Western blot. ResultsTwelve hours after CLP， the intestinal pathological scores significantly increased in the DMCLP group （P<0.05）. The results of western blot and RT-PCR showed the expressions of intestinal Occludin and ZO-1 protein were decreased in the DMCLP group， while the expression of inflammatory cytokines TNF-α， IL-1β and IL-6 mRNA was increased significantly （P<0.05）. The results of immunofluorescence and RT-PCR showed the number of macrophages in the intestinal tissue of mice in the DMCLP group increased significantly， and the expression of M1 markers iNOS and CRR7 mRNA increased significantly （P<0.05）. In further cell experiment， the expressions of M1 macrophages marker CD86 and inflammatory cytokine TNF-α， IL-1β and IL-6 mRNA were significantly increased in the HG+LPS group. ConclusionHigh glucose might aggravate intestinal injury by promoting LPS-induced macrophage polarization to M1 type.

Objective::To observe the effect of Bimin decoction(BMD) on nuclear factor-kappa B(NF-κB) signaling pathway and aquaporin 5(AQP5) expression in allergic rhinitis (AR) rats with lung and spleen Qi deficiency syndrome(LSQDS), in order to study the mechanism in treating AR. Method::Fifty-six SD rats were randomly divided into seven groups: control group, AR group, LSQDS AR group, BMD low dose two weeks group and four weeks group, BMD high dose two weeks group and four weeks group. The control group did not intervened, the AR group established the AR disease model with ovalbumin (OVA) as the allergen, the other five groups established the LSDQS model with smoke and senna gavage, and also established the AR disease model with OVA sensitization at the same time as the AR group. After the model was established successfully, four BMD intervention groups were separately given low dose BMD (11.3 g·kg^-1) for 2 weeks and 4 weeks, and high dose BMD (22.6 g·kg^-1) for 2 weeks and 4 weeks. To observe the general situation of the rats, hematoxylin eosin (HE) staining was used to observe the pathological changes of the nasal mucosa, immunohistochemistry and Western blot were used to detect the expression levels of NF-κB and AQP5, real-time fluorescent quantitative polymerase chain reaction technique (Real-time PCR)was used to detect mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6). Result::The typical AR symptoms were found in AR rats, the AR symptoms and lung and spleen Qi deficiency symptoms were found in AR rats with LSQDS at the same time, and the AR symptoms and lung and spleen Qi deficiency symptoms were significantly improved after the intervention of BMD. Compared with the control group, the typical histopathological changes of nasal mucosa were found in AR group and LSQDS AR group, with a higher behavioral score (P<0.05), and the expression of NF-κB and AQP5 protein increased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA increased (P<0.05). Compared with AR group, the pathological changes of nasal mucosa in LSQDS AR group were more serious, and the expression of NF-κB protein in nucleus increased (P<0.05), the expression of TNF-α and AQP5 mRNA increased (P<0.05). Compared with LSQDS AR group, the pathological changes of nasal mucosa in the groups which interfered by BMD were improved, and the expression of NF-κB and AQP5 protein decreased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA decreased (P<0.05). Compared with BMD low-dose two-week group, the expression of NF-κB protein in nucleus decreased (P<0.05) in BMD high dose four week group. Conclusion::Compared with AR group, the AR condition of the rats with LSQDS is more serious under the same allergen stimulation, BMD can treat AR and reduce the over secretion of glands, which may be related to inhibit the expression of AQP5 by inhibiting the NF-κB signaling pathway.