BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
BACKGROUND Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even lesscommon. The clinical prognosis of GC with bone metastasis is poor given the lackof an effective treatment.CASE SUMMARY A 70 y...BACKGROUND Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even lesscommon. The clinical prognosis of GC with bone metastasis is poor given the lackof an effective treatment.CASE SUMMARY A 70 year old man was referred to Shaoxing People’s Hospital with left chest painand slight dyspnea. Chest computed tomography (CT) revealed a metastaticlesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers inthe angle and antrum of the stomach, and tumor biomarkers including CEA andCA-199 were clearly increased. In addition, lymph node metastasis in the lessercurvature of the stomach was identified by positron emission tomography/CTscanning. Further pathological examination confirmed metastatic adenocarcinomain the rib and medium-low differentiated adenocarcinoma in the gastric space.The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB).Based on multidisciplinary team opinions, the patient received five courses ofchemotherapy (CAPOX plus aptinib), and then underwent rib resection andlaparoscopic radical distal gastrectomy. The patient started four courses ofchemotherapy after surgery, and then capecitabine and aptinib were administeredorally for 3 mo. Follow-up was performed on an outpatient basis usingabdominal/chest CT and tumor biomarkers. The patient exhibited an overallsurvival greater than 2 years, and the disease-free survival was approximately 18mo. His adverse events were tolerable.CONCLUSION The incidence of GC with rib metastases is extremely low, and patients can obtainmore benefits from individualized treatment formulated by multidisciplinaryteam. Chemotherapy plus surgery might represent an alternative option for GCwith rib metastasis.展开更多
Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence sho...Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-7 （PPAR-7） agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-7 and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. Methods： Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups： ControliaK242, IgANTAK242, toll-like receptor 4 inhibitor （TAK242） groups （rats were administrated with TLR4 inhibitor, TAK242） and Controlpo, IgANpo, Pio groups （rats were administrated with PPAR-y agonist, pioglitazone）. Urinary albumin-to-creatinine ratio （ACR）, serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin- 1 beta （IL- 1β） message ribonucleic acid （mRNA） and protein expression in renal tissues. Results were presented as mean -4- standard deviation. Differences between groups were analyzed by one-way analysis of variance. Results： Compared to normal rats, experimental rats showed higher ACR （4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P 〈 0.05）, obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-Iβ （48.28 ± 13.49 μg/ml vs. 35.56 ± 7.41μg/ml, P 〈 0.05）, and renal expression of IL-Iβ and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-Iβ, and serum IL- 1 β were decreased in rats treated with TAK242, and the expression ofTLR4 mRNA and protein was significantly reduced in Pio group compared to IgANpo group （1.22 4± 0.28 vs. 1.72 ± 0.45, P 〈 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P 〈 0.01）. Conclusions： Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.展开更多
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
文摘BACKGROUND Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even lesscommon. The clinical prognosis of GC with bone metastasis is poor given the lackof an effective treatment.CASE SUMMARY A 70 year old man was referred to Shaoxing People’s Hospital with left chest painand slight dyspnea. Chest computed tomography (CT) revealed a metastaticlesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers inthe angle and antrum of the stomach, and tumor biomarkers including CEA andCA-199 were clearly increased. In addition, lymph node metastasis in the lessercurvature of the stomach was identified by positron emission tomography/CTscanning. Further pathological examination confirmed metastatic adenocarcinomain the rib and medium-low differentiated adenocarcinoma in the gastric space.The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB).Based on multidisciplinary team opinions, the patient received five courses ofchemotherapy (CAPOX plus aptinib), and then underwent rib resection andlaparoscopic radical distal gastrectomy. The patient started four courses ofchemotherapy after surgery, and then capecitabine and aptinib were administeredorally for 3 mo. Follow-up was performed on an outpatient basis usingabdominal/chest CT and tumor biomarkers. The patient exhibited an overallsurvival greater than 2 years, and the disease-free survival was approximately 18mo. His adverse events were tolerable.CONCLUSION The incidence of GC with rib metastases is extremely low, and patients can obtainmore benefits from individualized treatment formulated by multidisciplinaryteam. Chemotherapy plus surgery might represent an alternative option for GCwith rib metastasis.
文摘Background： In vitro experiments have revealed that toll-like receptor 4 （TLR4） pathway is involved in the progression ofimmunoglobulin A nephropathy （IgAN） by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-7 （PPAR-7） agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-7 and TLR4 in IgAN has not been fully studied both in vitro and in vivo. In this study, we explored whether TLR4 pathway attributed to the progression of IgAN in experimental rats. Methods： Bovine gamma globulin was used to establish IgAN model. Fifty-four Lewis rats were randomly divided into six groups： ControliaK242, IgANTAK242, toll-like receptor 4 inhibitor （TAK242） groups （rats were administrated with TLR4 inhibitor, TAK242） and Controlpo, IgANpo, Pio groups （rats were administrated with PPAR-y agonist, pioglitazone）. Urinary albumin-to-creatinine ratio （ACR）, serum creatinine, and blood urea nitrogen were detected by automatic biochemical analyzer. Renal histopathological changes were observed after hematoxylin-eosin staining, and the IgA deposition in glomeruli was measured by immunofluorescence staining. Real-time polymerase chain reaction and Western blotting were used to detect TLR4 and interleukin- 1 beta （IL- 1β） message ribonucleic acid （mRNA） and protein expression in renal tissues. Results were presented as mean -4- standard deviation. Differences between groups were analyzed by one-way analysis of variance. Results： Compared to normal rats, experimental rats showed higher ACR （4.45 ± 1.33 mg/mmol vs. 2.89 ± 0.96 mg/mmol, P 〈 0.05）, obvious IgA deposition with mesangial hypercellularity, hyperplasia of mesangial matrix accompanied by increased serum IL-Iβ （48.28 ± 13.49 μg/ml vs. 35.56 ± 7.41μg/ml, P 〈 0.05）, and renal expression of IL-Iβ and TLR4. The biochemical parameters and renal pathological injury were relieved in both TAK242 group and Pio group. The expressions of renal tissue TLR4, IL-Iβ, and serum IL- 1 β were decreased in rats treated with TAK242, and the expression ofTLR4 mRNA and protein was significantly reduced in Pio group compared to IgANpo group （1.22 4± 0.28 vs. 1.72 ± 0.45, P 〈 0.01, and 0.12 ± 0.03 vs. 0.21 ± 0.05, P 〈 0.01）. Conclusions： Our study proves that inflammation mediated by TLR4 signaling pathway is involved in the progression of IgAN in rat models. Moreover, pioglitazone can inhibit the expression of TLR4 in IgAN.
