Exploring the clinical outcomes and safety profile of inetetamab treatment in metastatic breast cancer patients: A multicenter assessment of a Chinese-origin recombinant Anti-HER2 monoclonal antibody.

BACKGROUND: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody. This study aimed to evaluate the efficacy and safety of inetetamab and predictive factors for response in HER2-positive metastatic breast cancer (MBC) patients. METHODS: A cohort of HER2-positive MBC patients who received inetetamab-based therapy between June 2020 and August 2021 was evaluated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Adverse events (AEs) were graded according to the National Cancer Institute Common Toxicity Criteria. RESULTS: A total of 141 patients were included in the final analysis. The median PFS of the entire cohort was 7.1 months. The median number of treatment lines administered was three. The ORR was 36.9 %, and the DCR was 80.9 %. The most frequently employed treatment strategy was inetetamab + chemotherapy (49/141, 34.8 %), followed by inetetamab + HER2-tyrosine kinase inhibitors (HER2-TKIs) + chemotherapy, inetetamab + pertuzumab + chemotherapy, inetetamab + endocrine treatment and inetetamab + HER2-TKIs. Cox multivariate analysis revealed that PFS was associated with liver metastasis (hazard ratio [HR] 2.112, 95 % confidence interval [CI] 1.334-3.343, p = 0.001), previous HER2-TKI treatment (HR 2.019, 95 % CI 1.133-3.597, p = 0.017) and estrogen receptor positivity (HR 0.587, 95 % CI 0.370-0.934, p = 0.024). The toxicity was tolerable, with neutropenia being the most common treatment-related grade 3/4 AE (14.9 %). CONCLUSION: Inetetamab demonstrates effectiveness with a manageable safety profile, offering a promising therapeutic option for HER2-positive breast cancer patients who have shown resistance to prior anti-HER2 treatments.

Angiotensin-receptor blocker losartan alleviates atrial fibrillation in rats by downregulating frizzled 8 and inhibiting the activation of WNT-5A pathway.

Atrial fibrillation (AF) is a common arrhythmia. Angiotensin-receptor blocker (ARB) is related to AF treatment. This study explored the mechanism of ARB in AF. AF rat models were established by Ach-CaCl2 mixed solution injection. Rats were treated with ARB by gavage and injected with pcDNA3.1-based frizzled homolog 8 (FZD8) overexpression plasmids (oe-FZD8) through the tail vein. The 12-lead electrocardiogram was recorded by biological signal acquisition and processing system and AF duration was recorded, and atrial effective refractory period (AERP) was monitored by electrophysiology. Atrial fibrosis degree, FZD8 messenger RNA and protein levels, collagen I, collagen III, transforming growth factor ß1 (TGF-ß1), fibronectin, α smooth muscle actin (α-SMA), WBT-5B, and p-JNK1/2 levels, interleukin 1 ß (IL-1ß) and interleukin 6 (IL-6) levels were detected by Masson staining, reverse transcription quantitative polymerase chain reaction, western blot assay, immunohistochemistry, and enzyme-linked immunosorbent assay. ACh-CaCl2-induced AF rats showed a large area of fused necrosis, abnormal collagen fibre proliferation, high atrial fibrosis degree, and increased atrial fibrosis area in atrial interstitium, elevated collagen I, collagen III, TGF-ß1, fibronectin, α-SMA, IL-1ß, and IL-6 levels, whereas these trends were averted by ARB treatment. FZD8 was highly expressed in AF rat myocardium. ARB repressed FZD8 expression, prolonged AERP and reduced AF incidence. FZD8 overexpression annulled the effects of ARB on improving AF rat myocardial fibrosis. ARB inactivated the WNT-5A pathway by suppressing FZD8. ARB inactivated the WNT-5A pathway by silencing FZD8, therefore, alleviating AF rat atrial fibrosis.

Factors influencing compliance in RRD patients with the face-down position via grounded theory approach.

Patients with rhegmatogenous retinal detachment (RRD) require face-down positioning (FDP) for 3-6 months or longer after pars plana vitrectomy (PPV) combined with silicone oil (SO) tamponade. This paper aimed to identify the factors that influenced FDP compliance. This study adopted semi-structured interviews with patients who require FDP after SO tamponade. Constructivist grounded theory was utilized in this study. The qualitative data was analyzed and coded via NVivo 11.0 through open coding, axial coding and selective coding. Twenty-four RRD patients were involved. The interviews yielded five main themes that defined home FDP compliance were identified: posture discomfort, doctor-patient communication, psychological factors, occupational character, and family factors. A theoretical model of the influencing factors of postural compliance of FDP was constructed based on the interview analysis. A variety of factors can affect FDP conformity. We can increase compliance of RRD patients by enhancing comfort, encouraging doctor-patient communication, providing comprehensive care, promoting community-based intervention, and strengthening family education.

Silencing long non-coding RNA zinc finger antisense 1 restricts secondary cerebral edema and neuron injuries after traumatic brain injury.

OBJECTIVE: To investigate the interaction of long non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1) in secondary cerebral edema (CE) and neuron injuries after traumatic brain injury (TBI) in a mouse model. METHODS: TBI mouse models was established by free-fall strike. Adeno-associated virus-short hairpin-ZFAS1 was administrated into mice via intracerebral injection to downregulate lncRNA ZFAS1. LncRNA ZFAS1 in mouse brain was examined. Neurological severity score (NSS), cerebral water content (CWC) and lesion volume were measured. The number of TUNEL-positive cells in brain tissue was accessed. Bax and cleaved caspase-3 in brain tissues were measured by western blot analysis, and pro-inflammatory factor levels were detected. RESULTS: LncRNA ZFAS1 expression was upregulated in mouse brain tissues 3 days after TBI modelling. After the knockdown of lncRNA ZFAS1, NSS, CWC and lesion volume were decreased, apoptotic gene levels were decreased and pro-inflammatory cytokine levels were reduced, suggesting that lncRNA ZFAS1 knockdown could alleviate TBI-induced brain injuries in mice. CONCLUSION: This study demonstrated that silencing lncRNA ZFAS1 inhibited TBI by quenching apoptosis, reducing inflammatory response and improving the recovery of neurological function in TBI mice. LncRNA ZFAS1 might function as a possible curative management in secondary CE and neuron injury in TBI mice.

Fingolimod Suppresses a Cascade of Core Vicious Cycle in Dry Eye NOD Mouse Model: Involvement of Sphingosine-1-Phosphate Receptors in Infiltrating Leukocytes.

Purpose: The purpose of this study was to evaluate the inhibitory mechanism of fingolimod and the involvement of sphingosine-1-phosphate receptors (S1PRs) and cytokines-matrix metalloproteinases (MMPs)/MAP kinases (MAPKs) signaling in a dry eye disease (DED) mouse model. Methods: Sixty-four male NOD mice (DED model) and 16 age-matched BALB/c mice were used. In a preliminary experiment, 16 NOD mice were randomly divided into a positive control group and fingolimod-treated groups, with 8 BALB/c mice serving as wild-type control. In a subsequent, separate study, 48 NOD mice were randomly divided into 6 groups: fingolimod-treated groups at three different concentrations (0.05%, 0.005%, and 0.001%), normal saline group, untreated group, and fingolimod+W146 group. Animals received normal saline or fingolimod eyedrops three times daily until euthanasia 2 months later. Mice in the fingolimod+W146 group received daily intraperitoneal injections of W146 (0.1 mg/kg/day). Proinflammatory mediators were assessed by a protein array. Activities of MMP-2 and MMP-9 were evaluated by zymography. MAPKs and S1PRs were examined by Western blots and immunohistochemistry. Infiltrating cells and inhibitory mechanisms were assessed. Results: In the positive control group, levels of inflammatory mediators and S1PRs were upregulated. By comparison, fingolimod treatment significantly suppressed such markers which were significantly reversed by W146 (P < 0.01). Importantly, by double immunofluorescence staining, leukocytes were confirmed involved in DED in the NOD mouse model. Conclusions: Leukocytes are involved in DED in the NOD mouse model. The therapeutic mechanisms of fingolimod may be associated with inhibitory roles of "cytokines-MMPs/MAPKs" cycle in NOD mouse ocular surface tissues by mediating S1PRs in infiltrating leukocytes.