Multicenter real world study on the efficacy and safety of eribulin for the treatment of advanced breast cancer / 中华肿瘤杂志

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.

Exogenous Local Hyperthermia at 41o C Is Effective to Eliminate Mouse Model of Sporotrichosis, Independent of Neutrophil Extracellular Traps Formation

Background@#Local hyperthermia is recommended for the treatment of patients with fixed cutaneous sporotrichosis, though the effectiveness and mechanisms of action remain elusive. While neutrophils represent the main inflammatory cells associated with sporotrichosis lesions, the issue of whether hyperthermia is involved with interactions between neutrophils and Sporothrix globosa remains unclear. @*Objective@#To evaluate the effect of local hyperthermia on sporotrichosis and determine whether local hyperthermia involves effects of neutrophils against Sporothrix. @*Methods@#For the in vivo study, mice were infected with yeast cells of S. globosa followed by treatment with local hyperthermia. In vitro, an isolated S. globosa strain was co-cultured with or without neutrophils and subjected under different temperatures. Immunofluorescence was used to assess the formation of neutrophil extracellular trap (NETs) were formed under these different culture conditions and the number of fungi colony forming units were compared. Results: Hyperthermia was significantly more effective in clearing the lesions in the mouse model, as compared to sham treatment. Neutrophils failed to exert any fungicidal effects against S. globosa in response to hyperthermia. Moreover, NETs were formed after interactionwith S. globosa, and the percentage of NETs formed was not significantly different at 41o C or 37o C. @*Conclusion@#While hyperthermia could serve as an effective therapy for fixed cutaneous sporotrichosis, this ability does not involve the formation of NETs.

Effect of Modified Yuquanwan Combined with Taohong Siwutang on Major Cardiovascular Risk Factors of Patients with Type 2 Diabetes / 中国实验方剂学杂志

Objective:To observe the efficacy of modified Yuquanwan combined with Taohong Siwutang on major cardiovascular risk factors of type 2 diabetes and its effect on inflammatory factors and endothelial function. Method:One hundred and sixty patients were randomly divided into control group (80 cases) and observation group (80 cases) by random number table. The control group was given Tianqi Jiangtang capsule 5 tablets/time,3 times/day. Bothgroups were taken orally. aspirin enteric-coated tablets, 0.1 g/time,1 time/day, insulin for injection or oral antidiabetic, simvastatin tablets, 20 mg/time, 1 time/day, and irbesartan tablets, 150 mg/time, 1 time/day.patients in observation group were added with modified Yuquanwan combined with Taohong Siwutang for 24 weeks, 1 dose/day, and a 48-week follow-up visit were paid. Blood glucose, lipid, blood pressure, fasting plasma glucose (FPG), blood sugar 2 h after meal (2 h PG), glycosylated hemoglobin (HbA1c), systolic (SBP) and diastolic pressure (DBP) were detected for every 8 weeks, and at the 8th, 16th, and 24th week after treatment, up-to-standard HbA1c, LDL-C, SBP, DBP and all of those indexes were recorded, and levels of blood glucose, lipids and blood pressure were compared at different time points. During the treatment and within the 72-week follow-up, cardiovascular events, stroke events, peripheral vascular events and microvascular complications were recorded. And levels of tumor necrosis factor-α (TNF-α), homocysteine (Hcy), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), endothelin (ET-1) and nitric oxide (NO) were detected, and at the 8th, 16th and 24th week after treatment, body mass index (BMI) was recorded. Result:At the 24th week after treatment, the compliance rate of HbA1c in observation group was 81.16%（56/69）, which was higher than 64.71%（44/68） in control group (χ2=4.701, P<0.05), and the compliance rate of SBP was 94.2%（65/69）, which was higher than 82.36%（56/68） in control group (χ2=4.662, P<0.05). At the 16th week and 24th week after treatment, the compliance rate of LDL-C were 79.71%（55/69） and 88.41%（61/69）, which were higher than 63.24%（43/68） and 70.59%（48/68） in control group (χ2=4.5642, χ2=5.108, P<0.05). At the 16th week, the comprehensive compliance rate (blood glucose, blood pressure, blood lipid) in observation group was 59.42%（41/49）, which was higher than 41.18% （28/68） in control group (χ2=4.559, P<0.05). At the 24th week, the comprehensive compliance rate in observation group was 69.57% （48/69）, which was higher than 51.47% （36/68） in control group (χ2=4.695, P<0.05). At the 16th week, the compliance rate of BMI was 60.87% （42/69）, which was higher than 39.71% （27/68）in control group (χ2=6.136, P<0.05). At the 24th week, the compliance rate of BMI was 72.46% （50/69）, which was higher than 52.94% （36/68） in control group (χ2=5.585, P<0.05). At the 16th week after treatment, levels of 2 h PG and HbA1cin observation group were lower than those in control group (P<0.05). At the 24th week after treatment, levels of FPG, 2 hPG, HbA1c, SBP and DBP were lower than those in control group (P<0.05). Levels of TNF-α, Hcy, IL-6, hs-CRP and ET-1 were lower than those in control group (P<0.01), while level of NO was higher than that in control group (P<0.01). During 72 weeks of observation period, the rate of adverse vascular events in observation group was 13.04%(9/69), which was lower than 30.88%(21/68) in control group (χ2=5.957, P<0.05). Conclusion:In addition to the conventional western medicine therapy, modified Yuquanwan combined with Taohong Siwutang can further control the main cardiovascular risk factors of patients with T2DM, improve the endothelial function of T2DM patients, inhibit the expression of pro-inflammatory factors, and reduce the incidence of adverse vascular events.

Shufeng Huoxue Formula suppresses proliferation and regulates melanin metabolism in murine B16 melanoma cells in vitro through autophagy pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of autophagy in the regulatory effect of Shufeng Huoxue Fumula (SFHXF) on the proliferation and melanin metabolism in cultured murine B16 melanoma cells.</p><p><b>METHODS</b>B16 cells were treated with solutions containing 0.12, 0.25, 0.49, 0.98, or 1.96 mg/mL SFHXF preparations, rapamycin (an autophagy inducer), or rapamycin+SFHXF. The changes in the proliferation of B16 cells were assessed using MTT assay, and tyrosinase activity and melanin content in the cells were determined. The expressions of autophagy-related proteins P62, p-mTOR, LC3B, and beclin 1 in the cells were detected using Western blotting.</p><p><b>RESULT</b>Compared with the blank control cells, treatments with SFHXF both in the presence and in the absence of rapamycin concentration-dependently inhibited the cell proliferation (P<0.05) and obviously increased tyrosinase activity and melanogenesis in B16 cells (P<0.05); 0.98 mg/mL SFHLF, rapamycin+0.98 mg/mL SFHXF, and 50 nmol/L rapamycin all significantly up-regulated the expressions of LC3B-II and beclin 1 and down-regulated the expressions of P62 and p-mTOR in the cells.</p><p><b>CONCLUSION</b>SFHXF can regulate melanin metabolism and enhance tyrosinase activity and melanogenesis through the autophagy pathway to inhibit the proliferation of B16 cells in vitro.</p>

Primary diffuse large B-cell lymphoma of testis: a clinicopathologic study of 14 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings and prognosis of primary diffuse large B-cell lymphoma (DLBCL) of testis.</p><p><b>METHODS</b>Fourteen cases of primary DLBCL of testis, diagnosed according to the 2001 World Health Organization staging standards for hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemical study was performed and follow-up information analyzed.</p><p><b>RESULTS</b>The median age of the patients was 62 years. There were 10 patients in stage I, 3 in stage II and 1 in stage IV. Follow-up information was available in 11 patients (78.6%). Three of which were still alive and eight died (with duration of survival ranging from 5 to 19 months). The patients usually presented with unilateral painless enlargement of testis. Histologically, the lymphoma cells of all cases showed a centroblastic appearance. One case belonged to the germinal center B cell-like subtype on immunohistochemical study, while the remaining 13 cases were classified as non-germinal center B cell-like subtype. Ten of the 14 cases (71.4%) showed overexpression of p53 protein. Most cases demonstrated high proliferation index. Six of the 14 cases (42.9%) were positive for bcl-2 protein. The overall 1-year, 2-year and 5-year survival rates were 45.5%, 17.0% and 17.0%, respectively.</p><p><b>CONCLUSIONS</b>Most cases with primary DLBCL of testis were of peripheral activated B-cell origin. The prognosis is usually not favorable, with propensity of local relapse and systemic dissemination. Accurate pathologic diagnosis relies on detailed histologic examination and immunohistochemical study.</p>

Inducing liver-derived dendritic cell proliferation by plasmid-IL-3 and CD40L genes in mice in vivo / 中华肝脏病杂志

<p><b>OBJECTIVES</b>Try to induce liver-derived dendritic cells proliferation by plasmid-IL-3 and CD40L genes in mice in vivo.</p><p><b>METHODS</b>Rapid tail-vein injection of large amounts of plasmid-carrying genes was performed to transfect genes in mice livers. Liver nonparenchymal cells were isolated by Percoll gradient centrifugation. Dendritic cell markers were detected and dendritic cells were sorted out by flow cytometry. Morphology of dendritic cells was studied microscopically (with Giemsa staining) and under scanning electron microscopy.</p><p><b>RESULTS</b>Liver nonparenchymal cells dramatically increased in the liver lobules, portal and periportal areas in the treated group, but not in the control group. B220+/DEC205+ dendritic cells were detected and sorted by flow cytometry. There were more B220+/DEC205+ dendritic cells (16.0%) in the experiment group than those in the control group (1.1%). Morphologically, the sorted B220+/DEC205+ cells showed irregular shaped nuclei, paucity of cytoplasmic granules and extensive cytoplasmic processes.</p><p><b>CONCLUSION</b>B220+/DEC205+ dendritic cells were expanded in vivo in mice livers by rapid tail-vein injection of plasmid-carrying genes encoding IL-3 and CD40L in a large amount. Inducing liver dendritic cell proliferation in vivo provides a more convenient way for studying the biology of these cells.</p>