Objective: To identify an optimal back-flush solution for leukocyte-depleted filters that maximizes peripheral blood mononuclear cell (PBMC) recovery with high viability, long-term storage stability, and sterility of the harvested residues, thereby providing a clinically translatable strategy. Methods: Three sterile bag-packaged solutions—Saline, Solvent, and Hanks' balanced salt solution (HBSS)—were used to back-flush randomly assigned leukocyte-depleted filters. Nucleated cell recovery rate and viability of the harvested residues were compared. The optimal solution identified was applied to an expanded sample set. PBMC viability and yield were evaluated after 1h vs 48h storage of the residues. PBMCs isolated from the residues were cryopreserved in liquid nitrogen for 1 month, followed by post-thaw comparisons of viability and T-cell expansion capacity. Results: The Solvent group achieved the highest and most consistent nucleated cell recovery rate. Post-flush recovery rate from filters after 400 mL whole blood processing was (21.3±1.6)% for the Solvent group, significantly higher than Saline group (19.2±6.3)% and HBSS group (11.2±5.0)%, with residues from all groups maintaining viability >90%. No biologically significant difference in residue viability was observed between 48h vs 1h storage groups (93.3±2.3)% vs (95.7±1.8)%). PBMC recovery rates from residues showed no statistical difference between 48h vs 1h storage groups [(48.2%±9.5%)vs (40.41%±8.35%), P>0.05], with (17.7±2.6)×10 cells. After 1-month cryopreservation and 10-day expansion, PBMCs isolated from 48-hour-stored residues retained (91.2±3.2)% viability and achieved a (61.9±15.9)-fold expansion. Conclusion: The bag-packaged Solvent, as a back-flush solution, enables sterile acquisition of leukocyte-depleted filter residues through closed-system tubing connections. These residues maintained PBMC viability and recovery rates after 48h storage at 2℃-8℃, with post-cryopreservation (1-month liquid nitrogen) viability and expansion capacity remaining stable. This protocol complies with blood bank regulatory criteria, addresses the concerns about the infectious window period in cell therapy raw materials, and provides a clinically translatable strategy for PBMC-based applications.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

OBJECTIVE: To explore the effect of concurrent administration of goserelin for ovarian function protection on the pathological complete response (pCR) rate and objective response rate (ORR) of neoadjuvant chemotherapy (NAC) in young breast cancer patients. METHODS: The study enrolled breast cancer patients aged 18-45 with clinical stages ⅡA~ⅢC from January 2016 to May 2020. According to patients' willingness, they were divided into two groups: Those who chose to receive goserelin to protect ovarian function during NAC (goserelin group) and those who did not (chemotherapy group). The pCR rate and ORR were compared between the two groups, and subgroup analysis was conducted for patients with different molecular subtypes. RESULTS: A total of 93 patients were included in this study (31 in the goserelin group and 62 in the chemotherapy group). After propensity score weighting (PSW) adjustment, baseline data such as age, preoperative clinical stage, postoperative pathological stage, pa-thological type, hormone receptor status, human epidermal growth factor receptor 2 (HER2) and Ki-67 expression, molecular subtypes, and chemotherapy regimens were well-matched between the two groups. There was no significant difference in the pCR rate between the goserelin group and the chemotherapy group, with rates of 29.0% and 25.8%, respectively (P=0.741). Similarly, there was no significant difference in ORR between the two groups (90.3% vs. 87.1%, P=0.746). Subgroup analysis revealed that among the patients with hormone receptor-positive tumors, there were no significant differences in pCR rate (6.3% vs. 7.7%, P=0.852) or ORR (87.5% vs. 82.1%, P=0.839) between the goserelin and chemotherapy groups. Among the patients with hormone receptor-negative tumors, there were also no significant differences in pCR rate (53.3% vs. 56.5%, P=0.847) or ORR (93.3% vs. 95.7%, P=0.975) between the two groups. One year after the completion of chemotherapy, the incidence of chemotherapy-induced amenorrhea (CIA) was significantly lower in the goserelin group compared with the chemotherapy group (9.5% vs. 33.3%, P=0.036). CONCLUSION For young breast cancer patients with clinical stages of ⅡA~ⅢC, there was no statistical difference in pCR rate and ORR whether or not using goserelin during NAC. However, it is still necessary to expand the sample size and carry out a longer follow-up to evaluate the effect of goserelin on the long-term survival of young patients.
Humans ; Goserelin/administration & dosage* ; Female ; Breast Neoplasms/pathology* ; Neoadjuvant Therapy/methods* ; Adult ; Middle Aged ; Young Adult ; Adolescent ; Chemotherapy, Adjuvant ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Treatment Outcome ; Receptor, ErbB-2

Objective To investigate the mental health conditions of the relatives of advanced malignant tumor patients. Method The semi-structured interviews were conducted to the relatives of 13 patients with advanced malignant tumor,followed by analysis with phenomenological research method.Result 3 themes were worked out: uncertainty,negative physical and mental experiences and adjustment of perceptions.Conclusions The mental health of the relatives of advanced malignant tumor patients is on a poorer condition.Pertinent intervention measures should be taken to relieve their physical and mental pressures so as to improve their mental health status.

Objective To investigate the impacts of carvedilol combined with pravastatin,on aminoterminal pro-brain natriuretic peptide(NT-proNBP),cardiac troponin Ⅰ(cTnI)and cardiac function in coronary heart disease patients with chronic heart failure.Methods One hundred and tewnty five cases of coronary heart disease patients with chronic heart failure were randomly divided into the carvedilol group(63 cases)and carvedilol combined with pravastatin group(62 cases).In addition to using certain dosage of the above-mentioned drugs respectively,both groups underwent routine anti heart failure treatment with the course of 12 weeks.The class of heart function and changes of heart rate(HR) were observed before and after treatment.Left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD) and left ventricular ejection fraction(LVEF) were determined by using ultrasound heartbeat graph.Six min walk test(6MWT)was also observed before and after treatment and the level of NT-proBNP and cTnI level were determined by using an enzyme immunoassay method.And patients readmission rates and the incidence of cardiovascular events were also observed.Results The condition of carvedilol and pravastatin group were improved after treatment compared with before treatment[HR:(78±12) CICCS/min vs(100±112) CICCS/min,t =13.682,P ＜ 0.05 ;LVEDD:(43±5)mmvs(53±8)mm,t=5.284,P＜0.01;LVESD:(42±6)mmvs(56±7)mm,t=6.454,P＜0.01;LVEF:(50±5)％ and(35±8)％,t=-6.091,P<0.01);NT-proBNp:(986±713)ng/Lvs (3328±1109) ng/L,t =17.626,P ＜ 0.05) ; CInI:(0.85±0.16) μg/L vs(2.03±0.63) μg,/L,t =5.879,P ＜ 0.01 ;6MWT:(355.6±92.5)m vs(238.8±101.4) m,t =-8.255,P ＜ 0.01].After 3 months follow-up,the condition of carvedilol combined with pravastatin group were better than carvedilol group;LVEDD:(43±5)mm vs(57±6)mm,t =5.892,P ＜0.05 ;LVESD:(42±6)mm vs(49±7) mm.t =3.243,P ＜0.01 ;LVEF:(50±5) ％ vs(42±8) ％,t =-12.036,P ＜ 0.01 ; NT-proBNP:(986±713) ng/L vs(1626±968) ng/L,t =3.603,P ＜0.01 ;cTnI:(0.85±0.16) μg/L vs(1.15±0.36) μg/L,t =3.200,P ＜ 0.01 ;6MWT:(355.6±92.5) mvs(296.2±99.5) m,t =-10.119,P ＜ 0.01].The rehospitalization rate(3.3 ％ vs 12.7％,x2 =6.224,P ＜ 0.05) and the incidence of cardiovascularevents(3.3％ vs 15.9％,x2 =5.974,P ＜ 0.05) were both decreased Significantly after treated with carvedilol combined with pravastatin.Conclusion Carvedilol combined with pravastatin can reduce the level of NT-proBNP and cTnI,improve heart function in coronary heart disease patients with chronic heart failure.