Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective: In ovarian cancer (OvCa), tumor cell high glucocorticoid receptor (GR) has been associated with poor patient prognosis. In vitro, GR activation inhibits chemotherapyinduced OvCa cell death in association with transcriptional upregulation of genes encoding anti-apoptotic proteins. A recent randomized phase II study demonstrated improvement in progression-free survival (PFS) for heavily pre-treated OvCa patients randomized to receive therapy with a selective GR modulator (SGRM) plus chemotherapy compared to chemotherapy alone. We hypothesized that SGRM therapy would improve carboplatin response in OvCa patient-derived xenograft (PDX). Methods: Six high-grade serous (HGS) OvCa PDX models expressing GR mRNA (NR3C1) and protein were treated with chemotherapy +/− SGRM. Tumor size was measured longitudinally by peritoneal transcutaneous ultrasonography. Results: One of the 6 GR-positive PDX models showed a significant improvement in PFS with the addition of a SGRM. Interestingly, the single model with an improved PFS was least carboplatin sensitive. Possible explanations for the modest SGRM activity include the high carboplatin sensitivity of 5 of the PDX tumors and the potential that SGRMs activate the tumor invasive immune cells in patients (absent from immunocompromised mice). The level of tumor GR protein expression alone appears insufficient for predicting SGRM response. Conclusion The significant improvement in PFS shown in 1 of the 6 models after treatment with a SGRM plus chemotherapy underscores the need to determine predictive biomarkers for SGRM therapy in HGS OvCa and to better identify patient subgroups that are most likely to benefit from adding GR modulation to chemotherapy.

Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5)exposure induced damage to pulmonary blood-air barrier.Methods Eighteen male BALB/C mice (aged of 10 weeks,weighing 24～27 g)were randomly divided into control group and low-and high-dose PM2.5 exposure groups (receiving 1 .8 and 16.2 mg/kg,respectively),with 6 mice in each group.The control group received tracheal instillations of normal saline on days 1,4,and 7,whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points.In 24 h after last exposure,pathological changes in the lung tissues were observed,and the contents of total protein (TP ),lactate dehydrogenase (LDH ),and alkaline phosphatase (AKP ) in bronchoalveolar lavage fluid (BALF ),and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues.Additionally,an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells.In combination with a THP-1 macrophage model,the supernatant PM2.5 supernatant,macrophage supernatant,and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h,respectively.Transmembrane electrical resistance (TEER),sodium fluorescein permeability of the barrier model,and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure.Furthermore,the expression of inflammatory cytokines,such as TNF-α,IL-1β,IL-6,and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR)and enzyme-linked immunosorbent assay (ELISA).Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner,significantly elevated the contents of TP,LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue,especially the high-dose exposure when compared with the mice from the control group (P<0.01 ).In vitro barrier model exposure experiments showed that in comparison with the treatment of 150 and 300 μg/mL PM2.5 and macrophage supernatant,the same doses of PM2.5-macrophage supernatant resulted in notably decreased TEER and significantly enhanced permeability in the barrier model (P<0.01 ),and markedly increased LDH release from epithelial and endothelial barrier cells (P<0.01 ).Additionally,the exposure of 150 and 300μg/mL PM2.5 led to a significant up-regulation of TNF-α,IL-1β,IL-6,and IL-8 in the macrophages (P<0.01 ).Conclusion Macrophages deteriorate PM2.5-induced functional impairment of the pulmonary blood-air barrier.

ObjectiveTo investigate common dyadic coping (CDC) in linking with marital satisfaction and quality of life (QOL) in patients with brain injury and their spouses in a rehabilitation facility by using common fate model (CFM). MethodsFrom October, 2022 to June, 2023, 101 brain injury inpatients and their spouses in Beijing Bo'ai Hospital completed the questionnaire of Dyadic Coping Inventory, Kansas Marital Satisfaction Scale and World Health Organization Quality of Life. ResultsThe level of CDC between patients and their spouses significantly positively correlated with their marital satisfaction for both partners (β = 0.814, P < 0.001), as well as correlated with their quality of life (β = 0.271, P = 0.038; β = 0.481, P < 0.001). For the dimensions of QOL, the physical, psychological, social relationship and environmental dimensions significantly positive correlated with the CDC for the spouses, and only psychological and social relationship dimensions for the patients. ConclusionFacing the stress of brain injury, the level of CDC within couples can positively predict their marital satisfaction and QOL, and effect seems stronger for the spouses. It is advisable to consider both brain injured patients and their spouses as a whole to promote psychological adaptation and improve rehabilitation outcomes.

OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway.

OBJECTIVE To study the improvement effects of Huorongcaohuangqi （HRCHQ） admixture decoction on mesangial proliferative glomerulonephritis （MsPGN）model rats and its mechanism . METHODS Totally 70 rats were divided into sham operation group （n＝10）and modeling group （n＝60）according to body weight . Sham operation group underwent sham operation，and MsPGN model was induced by immunological method （Freund’s adjuvant+BSA+lipopolysaccharide ）in modeling group. After successfully modeling ，50 rats were randomly divided into model group ，HRCHQ high -dose，medium-dose and low - dose groups （4.05，2.03，1.02 g/kg），Benazepril hydrochloride tablet group （20 mg/kg），with 10 rats in each group . Sham operation group and model group were given distilled water intragastrically ；other groups were given relevant medicine intragastrically 15 mL/kg，once a day ，for consecutive 5 weeks. After last administration ，the contents of total protein ，albumin and urea nitrogen were determined in the serum of rats . The expressions of transforming growth factor β1（TGF-β1）and tumor necrosis factor α（TNF-α）in renal tissue were detected by immunohistochemistry ；the expression of complement C 3 in renal tissue was detected by immunofluorescence . The phosphorylation level of phosphatidylinositol 3 kinase/protein kinase B/glycogen synthase kinase 3β（PI3K/Akt/GSK-3β） signal pathway related proteins and expression level of fibronectin （FN） in renal tissue were detected by Western blot . RESULTS Compared with model group，the serum contents of total protein and albumin were increased significantly in HRCHQ high -dose group （P＜0.05 or P＜0.01）. The serum content of urea nitrogen ， the E-mail：Houxia_75@163.com expressions of TGF -β1，TNF-α，FN and complement C 3，and the phosphorylation levels of PI 3K，Akt and GSK 3β protein were all decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS HRCHQ can improve MsPGN by reducing the proliferation of mesangial cells and inhibiting the activity of PI 3K/ Akt/GSK3β signaling pathway .

Objective To investigate the effect of Exosomes derived from lung cancer cells on the migration of secretory cells and homologous tumor cells and to explore the role of PI3K/Akt and SRC signaling pathways in this process.Methods Exosomes were isolated from the supematant post density gradient centrifugation of A549,lung cancer cells.Morphology of the Exosomes was studied using transmission electron microscopy.Protein expression was analyzed using Western blotting.Cell migration was analyzed by a transwell assay.Results The double-membrane-bound Exosomes appeared as discal-shaped structures,30-100 nm in diameter.Western blotting showed that CD9 was abundant in the Exosomes.The Exosomes promoted the migration of A549 cells and their homologous tumor cells,HCC827 in a dose-dependent manner,accompanied by the activation of Akt and SRC.Conclusion The Exosomes derived from A549 (lung cancer) cells promote the migration of the secreting cells and the homologous tumor cells.The mechanism may be correlated with the activation of Akt and SRC.

Objective To explore the effect of Exosomes isolated from the A549 lung cancer cells on the proliferation of these cells and their ho?mologous tumor cells,HCC827,and the role of the PI3K/Akt and SRC signaling pathways in this process. Methods Exosomes were isolated from the supernatant after density gradient centrifugation of A549 cells. The Exosomes morphology was observed by transmission electron microscopy. The expression of the Exosome?specific proteins was analyzed using Western blotting. Cell proliferation was investigated using the MTT assay. Re?sults The A549?derived Exosomes were 30?100 nm in diameter and had a bilayer membrane.Western blotting showed that CD9 was detected in these Exosomes. The isolated Exosomes promoted the proliferation of the A549 and the HCC827 cells in a dose?and time?dependent manner,ac?companied by the activation of Akt and SRC. Conclusion Exosomes isolated from A549 cells promote the proliferation of the secreting cells and the homologous tumor cells in a dose?and time?dependent manner. The mechanism may be related to the activation of Akt and SRC.

Objective To observe ghrelin expression in gastric tissue and serum leptin level of the early over-fed rats given ω-3 polyunsaturated fatty acids (PUFAs) diets after weaning,and explore the effects of early over-feeding and diets intervention on the metabolic syndrome in adult rats.Methods Male Sprague-Dawley rats were divided into normal feeding group (NF group,10 per litter) or over-feeding group (OF group,3 per litter) in postnatal day 3,and then different diets were given after weaning (postnatal day 21).The OF group was separately given conventional diet (OF + Con group),high-fat diet (OF + HF group),or ω-3 PUFAs (OF + ω-3 group) ; while the NF group was separated into NF + Con group and NF + HF group.Body weight and food intake were recorded every week.In week 6 and week 16,glucose tolerance test was perforfmed.Serum leptin,ghrelin,and triglyceride were assayed by enzyme-linked immuno-absorbent assay.Ghrelin mRNA and protein levels in gastric tissue were quantified by real-time PCR and immunohistochemistry.Results At week 16,energy intake,body weight and glucose intolerance in OF + HF group were significantly higher than in NF + HF group (t =-3.453,P =0.014 ; t =-6.406,P =0.000 ; F =16.249,P =0.000),and serum triglycerides,ghrelin mRNA of gastric tissue were significantly higher than those of OF + Con group (t =4.72,P =0.005 ; t =8.486,P =0.000).At week 16,the serum leptin level in OF + Con group was higher than that in NF + Con group (t =-3.274,P =0.031),also higher in OF + HF group than that in OF + Con group (t =3.028,P =0.014).There were no significant differences in serum ghrelin and the area of ghrelin immuno-positive cells in the gastric tissue among groups.The above indicators in OF + ω-3 group were not different from those of NF + Con group.Conclusions Over-feeding during the lactation period may lead to high susceptibility to obesity and disordered glucose and lipid metabolism.It can also increase serum leptin and ghrelin mRNA expression in gastric tissue,aggravate leptin resistance and feeding control disorders.Dietary ω-3 PUFAs offered protection against excessive accumulation of adipose tissue,glucose intolerance,leptin resistance,and maintained normal levels of leptin and ghrelin.