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With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.
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Objective:To investigate the safety and feasibility of Ivor-Lewis procedure under uniportal video-assisted thoracoscopy(VATS) for esophageal cancer and Siewert type I esophago-gastric junction carcinoma.Methods:The patients with middle-lower segment esophageal cancer or Siewert type I esophago-gastric junction carcinoma received minimally invasive esophagectomy between October 2020 and June 2021, and the clinical data was collected and analyzed.Results:26 patients received Ivor-Lewis procedure underwent uniportal VATS, while 45 patients underwent McKeown surgery under multiport VATS. The average operation time of patients in the two groups were(265±110)min and (235±94)min, and the average intraoperative blood loss were(80±57)ml and(105±60)ml. The mean number of lymph nodes removed in the surgery were (19.3±2.9) and 18.6±2.7 respectively in two groups, and the mean length of hospital stay was(7.5±3.5)days and(8.3±2.7)days. The incidence of perioperative complications were not significantly different in two groups. The VAS score of patients received Ivor-Lewis procedure underwent uniportal VATS was lower than that of patients received McKeown surgery in ostoperative day 1, day 3, day 7 and 1 month. The difference was statistically significant in two groups( P<0.05). Conclusion:The Ivor-Lewis procedure under uniportal VATS for esophageal cancer and Siewert type I esophago-gastric junction carcinoma has the advantage of less postoperative pain, and the procedure is feasible in clinical practice.
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Objective: Sweet Tea (ST), derived from the leaves of Lithocarpus polystachyus, is a Chinese folk medicine with wide pharmacological activities. However, the promotive effects of ST water extract on hepatocytes proliferation and its underlying mechanism remains still unknown. In the present study, the beneficial effects of ST water extract on human hepatocytes and its possible mechanism were investigated. Methods: MTT assay was used to detect the safety range of ST; HL7702 cells were divided into four groups: control group, ST low- (50 μg/mL), medium- (200 μg/mL) and high-concentration (800 μg/mL) groups; BrdU ELISA and EDU staining were used to observe DNA content and cell proliferation; Moreover, flow cytometry was applied to analyze the distribution of cell cycle. Furthermore, the expression of cyclin D1, CDK4, HGF/c-Met, Akt, Erk1/2 were detected by Western blot. Results: It was found that ST water extract concentration-dependent promoted human hepatocytes HL7702 cell proliferation within 72 h through accumulating the cells in S phase and G2/M phase. Furthermore, ST water extract up-regulated expression of Cyclin D1 and CDK4 proteins. Moreover, ST water extract not only increased HGF expression and phosphorylation of c-Met level, but also activated the phosphorylation levels of AKT, ERK1/2. Interestingly, both of AKT inhibitor A6730 and ERK1/2 inhibitor U0126 reversed the promotive effects of ST water extract, which further confirmed that activation of AKT and ERK1/2 were involved. Conclusion: The findings reveal that ST water extract promoted HL7702 cells proliferation through the stimulation of cell cycle mediated by activating the AKT- and ERK1/2-related pathway.
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OBJECTIVE@#To explore the effects of matrine on the proliferation, tumor cell stemness, β-catenin transcriptional activity and AKT/GSK3β/β-catenin signaling pathway in human hepatocellular carcinoma (HCC) HepG2 and Huh7 cells.@*METHODS@#The proliferation and colony formation ability of HepG2 and Huh7 cells treated with 200, 400, and 800 μg/mL matrine were evaluated with MTT assay and colony formation assay, respectively. Real-time quantitative PCR was performed to detect the mRNA expressions of CD90, epithelial cell adhesion molecule (EpCAM) and CD133, and dual-luciferase assay was used to detect the transcriptional activity of β-catenin in the treated cells. The effects of matrine on the expressions of protein kinase B (AKT), P-AKT, GSK-3β, P-GSK-3β, P-β-catenin and β-catenin proteins in the Wnt/β-catenin signaling pathway were assessed using Western blotting.@*RESULTS@#Matrine inhibited the proliferation of the two HCC cell lines in a time- and concentration-dependent manner. The half-inhibitory concentrations of matrine were 2369, 1565 and 909.1 μg/mL at 24, 48 and 72 h in HepG2 cells, respectively, and were 1355, 781.8, and 612.8 μg/mL in Huh7 cells, respectively. Matrine concentrationdependently suppressed colony formation of the HCC cells, producing significant inhibitory effects at 400 μg/mL < 0.01) and 800 μg/mL < 0.001) in HepG2 cells and at 200 μg/mL < 0.05), 400 μg/mL < 0.01), and 800 μg/mL < 0.001) in Huh7 cells. Matrine at 400 and 800 μg/mL significantly inhibited the mRNA expression of CD90, EpCAM and CD133 and the transcriptional level of β-catenin in both HepG2 and Huh7 cells < 0.05 or 0.01). Matrine at 400 and 800 μg/mL also significantly decreased the protein levels of β-catenin, P-AKT and P-GSK-3β and increased the phosphorylation level of β-catenin in both of the cell lines.@*CONCLUSIONS@#Matrine inhibits the proliferation, colony formation, and the expressions of tumor stem cell markers CD90, EpCAM and CD133 in both HepG2 and Huh7 cells probably by inhibiting Wnt/β-catenin signaling pathway and the transcriptional activity ofβ-catenin.
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This study reported the outcome of a case of fetal hemolytic disease after multiple intrauterine transfusions due to Rh incompatibility between the mother and fetus. The pregnant women had a history of termination for fetal edema at 29 weeks of gestation due to undecided reason as no relevant tests were conducted. Fetal edema was found and hemolytic disease (severe anemia) was diagnosed at 24 gestational weeks in the index pregnancy. After five intrauterine transfusions, fetal edema and anemia were improved. The baby who was born by cesarean section at 33 gestational weeks, was diagnosed with hemolytic disease and transferred to the neonatology department. After one month of treatment, the baby was improved and discharged. Whereafter he was followed up to one year of age without any abnormality in physical or mental development.
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This study reported the outcome of a case of fetal hemolytic disease after multiple intrauterine transfusions due to Rh incompatibility between the mother and fetus. The pregnant women had a history of termination for fetal edema at 29 weeks of gestation due to undecided reason as no relevant tests were conducted. Fetal edema was found and hemolytic disease (severe anemia) was diagnosed at 24 gestational weeks in the index pregnancy. After five intrauterine transfusions, fetal edema and anemia were improved. The baby who was born by cesarean section at 33 gestational weeks, was diagnosed with hemolytic disease and transferred to the neonatology department. After one month of treatment, the baby was improved and discharged. Whereafter he was followed up to one year of age without any abnormality in physical or mental development.
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Objective To observe the expression of PD-L1 in breast cancer tissue and to investigate its correlation with cellu-lar immunity.Methods One hundred and fourteen paraffin-embedded specimens of breast cancer were collected from the Qian′an Municipal People′s Hospital.The expression of PD-L1 in breast tumor tissue was detected by immunohitochemical technique,then the relationship between PD-L1 expression and tumor clinicopathological characteristics was analyzed;the levels of peripheral blood CD3+,CD3+CD4+,CD3+CD8+,CD3-CD19+,CD3-CD16+CD56+cells and CD4+/CD8+in the patients with PD-L1 negative and PD-L1 positive of the two groups were detected by the flow cytometry.Results Among 114 cases of breast cancer specimen,35 ca-ses(30.7%)were PD-L1 expression positive with the expression rate of 30.7%.The PD-L1 expression was correlated with the tumor size,histological grade and Ki-67 high expression(P<0.05);the cellular immunity status in the patients with PD-L1 negative expression was better than that in the patients with PD-L1 positive expression(P<0.05).Conclusion The PD-L1 expression is closely correlated with the poorer clinicopathological characteristics of breast cancer,its mechanism may be correlated with the dis-ruption of cellular immunity in the patients with PD-L1 positive expression.
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Molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization using ribavirin as the template molecule and methacrylic acid as the functional monomer.The sensitive film of ribavirin electrode was constructed by molecularly imprinted polymer doped with graphene oxide as the ionophore, poly(vinylchloride) (PVC) as matrix and dioctyl sebacate for plasticizer.The results showed that the best performance of the electrode was obtained when the sensitive film compositions were 100.8 mg of MIP, 14.7 mg of GO, 450.8 mg of PVC and 901.6 mg of dioctyl sebacate, and the inner filling solution composition was 0.1 mol/L NaCl + 0.05 mol/L NaAc-0.05 mol/L HAc + 1.0×10.-5 mol/L ribavirin solution.The electrode showed a near-Nernstian slope of 45.565 mV/decade for ribavirin over the range of 1.0×10.6-1.0×10.-4 mol/L and a detection limit of 1.0×10.-7 mol/L.The electrode could be used in the pH range of 3 to 5 with response time of less than 3 min.The developed electrode exhibited high selectivity for ribavirin and was successfully applied to the determination of ribavirin in feed and injection with recoveries of 90%-110% and RSD of 3.0%-7.9%.
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The traditional view that vitamin D is mainly involved in bone metabolism and calcium and phosphorus homeostasis,and bone-related diseases such as osteoporosis related.However,some recent studies have shown that vitamin D plays a key role in obstetrics and gynecology diseases,particularly,endometriosis and ovarian cancer,preeclampsia and gestational diabetes mellitus (GDM) in polycystic ovary syndrome influence (PCOS).Advances in vitamin D article and on the relationship between gynecological and obstetrical diseases were reviewed.
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[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.
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<p><b>OBJECTIVE</b>To optimize the experimental model of nitric oxide (NO) production in mouse peritoneal macrophages in response to lipopolysaccharides (LPS) stimulation.</p><p><b>METHODS</b>Mouse resident peritoneal macrophages were collected by lavaging the peritoneal cavity of mice with Hank's solution and stimulated with Pseudomonas aeruginosa LPS for NO production. NO concentration in the culture supernatants was measured with Griess Reagent. The influences of cell density, LPS concentration, LPS stimulation duration and culture medium volume on NO production were investigated. Finally, the feasibility of the model was confirmed with specific anti-inflammatory drugs.</p><p><b>RESULTS</b>The density of macrophages produced the most significant effect on NO production (P<0.001), and optimal results were obtained at the macrophage density of 6×10(6) cells/ml with a volume of 100 µl in each well in 96-well plate. At a LPS concentration below 1 µg/ml, NO production increased proportionally with the increment of LPS concentration (P<0.001), but the increment of NO production declined obviously at LPS concentrations beyond 1 µg/ml, and the peak NO production occurred at a LPS concentration of 10 µg/ml. NO production also increased significantly with the prolongation of LPS stimulation (P<0.05), and the increments were greater within 24-48 h than those in 48-72 h. NO content in the culture supernatant was associated with the medium volume, and the highest level occurred in a system volume of 100 µl. Aspirin (1 mmol/L), dexamethasone (10 µmol/L), and cyclosporin A (10 µmol/L) all significantly inhibited LPS-stimulated production of NO in mouse resident peritoneal macrophages (P<0.001).</p><p><b>CONCLUSIONS</b>Macrophage density, LPS concentration, and the duration of LPS stimulation are the main factors affecting LPS-stimulated NO production in mouse resident peritoneal macrophages. The optimal results can be obtained with a macrophage density of 5×10(6) cells/ml (100 µl per well), LPS concentration of 10 µg/ml, LPS stimulation duration of 24 h or 48 h, and a culture medium volume of 100 to 200 µl.</p>
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Animals , Female , Male , Mice , Cells, Cultured , Lipopolysaccharides , Pharmacology , Macrophages, Peritoneal , Bodily Secretions , Mice, Inbred Strains , Nitric OxideABSTRACT
<p><b>OBJECTIVE</b>To study the anti-inflammatory and analgesic activities of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (ZL-5010) in vivo and in vitro.</p><p><b>METHODS</b>The analgesic effect of ZL-5010 was evaluated by acetic acid-induced writhing response in mice, and the anti-inflammatory effects was assessed in mice with xylene-induced ear edema and in rats with carrageenan-induced paw edema. Mouse peritoneal exudate cells activated by bacterial lipopolysaccharides (LPS) were used to evaluate the anti-inflammatory effect of ZL-5010 in vitro. The levels of interleukin-1β (IL -1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>At the doses of 0.25 and 0.5 mmol/kg, ZL-5010 administered by gavage once daily for 3 days significantly reduced acetic acid-induced writhing frequency and suppressed xylene-induced ear edema in mice, and alleviated paw edema induced by carrageenan in rats (P<0.05). The agent also inhibited the production of the pro-inflammatory cytokines IL-1β and TNF-α by LPS-induced mouse peritoneal exudate cells in vitro, with the statistically significant minimum effective concentrations of 10 and 20 µmol/L, respectively (P<0.05).</p><p><b>CONCLUSION</b>ZL-5010 administered by gavage has anti-inflammatory and analgesic effects in mice and rats, and in mouse peritoneal exudate cell cultures, the agent also inhibits the production of the pro-inflammatory cytokines IL-1β and TNF-α.</p>
Subject(s)
Animals , Female , Male , Mice , Rats , Amino Acids, Diamino , Pharmacology , Therapeutic Uses , Analgesics , Pharmacology , Therapeutic Uses , Anti-Inflammatory Agents , Pharmacology , Therapeutic Uses , Cyclohexanes , Pharmacology , Therapeutic Uses , Interleukin-1beta , Metabolism , Mice, Inbred Strains , Pyrimidines , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Objective To determine the content of the heavy metal Cadmium(Cd)in Changtong oral liquid.Methods Inductively coupled plasma mass spectrometry(ICP -MS )was used.Results The calibration curve was linear in t he range of 0.0025～0.0125?g /mL for Cd(r=0.9997).The average recovery of the heavy me tal element of Cd was99.37%(n=5,RSD =2.73%).Conclusion This method is simple,accurate and e ffective.It can be used for the quality control of Changtong oral li quid.
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AIM: To determine the content of ferulic acid and rhein in Shengfaling Tincture(Radix Angelicae Sinensis,Flos Carthami,Radix Polygoni Multiflori,ect.). METHODS:HPCE was used.The best condition was obtained with a fuse dsilca capillary tube (60 cm?75 ?m,effective length of 53 cm),30 mmol?L -1 sodium tetraborate electrophoretic buffer(pH 8.2),at a constant voltage of 12 kV and temperature at 25 ?C .The UV detection wavelength was at 313 nm and caffeic acid was adopted as internal standard. RESULTS:The calibration curves was linear in the range of 2.4-12 ?g?mL -1 for ferulic acid(r=0.999 7) and 1.6-8 ?g?mL -1 for rhein (r= 0.999 6 ),respectively.The average recovery of ferulic acid was 99.06% and that of rhein was 98.94%. CONCLUSION: This method is simple,quick and sensitive.