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Small-cell lung cancer (SCLC) has a high degree of malignancy and is characterized by strong invasiveness, rapid growth, and early metastasis. SCLC is sensitive to initial treatment with chemotherapy and radiotherapy, but it can easily relapse and has a poor prognosis. Both programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antagonists activate the immune response of tumor cells by activating T cells, and have shown exciting curative effects in clinical studies of SCLC, thereby becoming powerful po-tential agents to treat SCLC in the future. This article aims to illustrate the progress of PD-1/PD-L1 inhibitors in the treatment of SCLC, as well as the role of PD-L1 expression and tumor mutation burden (TMB) as a biomarker in SCLC.
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Objective: In tumor microenvironment, immune-related mechanisms up-regulate the expression of programmed death li-gand 1 (PD-L1), which abnormally activates PD-L1 signaling pathway and mediates tumor immune escape. Soluble programmed death ligand 1 (sPD-L1) is a form of PD-L1. It has been confirmed that the expression of sPD-L1 in lung squamous cell carcinoma and adeno-carcinoma is related to disease progression, while small cell lung cancer (SCLC) has a high degree of malignancy, strong invasiveness and few related studies. The purpose of this study was to observe the changes in expression of sPD-L1 in the plasma of SCLC patients and their clinical significance. Methods: A total of 94 patients with SCLC diagnosed by pathological examination in Shanxi Provincial Cancer Hospital from March 2018 to November 2018 were selected as test group, and 17 healthy persons in the same period were se-lected as control group. The dynamic changes of plasma sPD-L1 were compared between the two groups, and the correlations among the expression of sPD-L1 and TNM stage, distant metastasis, and pro-gastrin-releasing peptide (ProGRP) was analyzed. Results: The lev-el of sPD-L1 in the test group was higher than that in the control group (P<0.05 and P<0.01, respectively). In patients with SCLC in the remission stage, the serum sPD-L1 level after chemotherapy was significantly lower than that before chemotherapy (P<0.01); in pa-tients with advanced stage, the serum sPD-L1 level after chemotherapy was significantly higher than that before chemotherapy (P<0.01). The abnormal high expression of sPD-L1 in SCLC patients was significantly correlated with the progression of the disease (P<0.05). The expression of sPD-L1 in serum was positively correlated with the tumor marker ProGRP. Conclusions: The expression of sPD-L1 in peripheral plasma of patients with SCLC is higher than that in healthy individuals and is closely related to the clinical effect.
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Lung cancer is the most common malignant tumor worldwide. There are more than 700000 new cases diagnosed as lung cancer each year in China, of which 80%-85% are non-small cell lung cancer (NSCLC). The mutation proportion of epidermal growth factor receptor (EGFR) may reach up to 40%-55%. EGFR-tyrosine kinase inhibitor (EGFR-TKI) has become the standard first-line treatment method for advanced NSCLC patients with EGFR mutation. Chinese oncologists have done a large number of clinical studies, providing an important evidence-based medicine proof for treatment of advanced NSCLC with EGFR mutation.
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Objective@#To observe the changes of PD-1 expression, mRNA level and cytotoxic activity of CD19 CAR-T cells during the culture process of CAR-T cells.@*Methods@#The peripheral blood T cells of 6 lymphoma patients with high expression of PD-1 and 6 healthy volunteers were the source of CAR-T cells. The expression of PD-1 was analyzed by flow cytometry. The mRNA level of PD-1 was analyzed by PCR. The cell proliferation was analyzed by CCK-8 assay. The cytotoxicity was analyzed by LDH assay.@*Results@#①The transfection efficiency of high PD-1 expression T cells and healthy volunteer T cells were as the same (P>0.05) . ②The cell proliferation capacity of CD19 CAR-T cells from high PD-1 expression T cells or healthy volunteer T cells, with or without PD-1 inhibitor were as the same (P>0.05) . ③The cytotoxicity to lymphoma cells of high PD-1 expression T cells and CAR-T cells were lower than that of these two T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer T cells (P<0.001) . There was no difference of the cytotoxicity between the CAR-T cells from high PD-1 expression T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer (P>0.05) . ④There was no difference of the expression of PD-1 in all CAR-T cell groups during the culture process (P>0.05) . There was no difference of mRNA level of PD-1 in all groups during the culture process (P>0.05) . ⑤The PD-1 expression of CAR-T cells increased by the time of culture after contacting with lymphoma cells (P<0.001) . The PD-1 inhibitors could antagonize this effect. There was no difference of mRNA level of PD-1 in all groups after contacting with lymphoma cells (P>0.05) .@*Conclusion@#The PD-1 expression of CAR-T cells from high PD-1 expression T cells increased by the time of culture after contacting with lymphoma cells. However, the mRNA level of PD-1 of all groups did not change, even if PD-1 inhibitor was applied.
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Objective To compare the outcomes of percutaneous Kirschner wire assisted reduction with minimally invasive plate osteosynthesis and open reduction with locking plate in treatment of Robinson type 2B midshaft clavicular fractures.Methods A retrospective case control study was conducted to analyze the clinical data of 96 patients with Robinson type 2B midshaft clavicular fracture from June 2009 to October 2016.There were 70 males and 26 females with an average age of 34.5 years.The patients were divided into two groups according to the different surgical methods:49 patients were treated with percutaneous Kirschner wire assisted reduction and minimally invasive locking plate osteosynthesis (minimally invasive group);47 patients were treated with open reduction with locking plate internal fixation (open plating group).According to the Robinson fracture typing,there were 28 patients with type 2B1 and 21 with type 2B2 in the minimally invasive group;there were 23 patients with type 2B1 and 24 with type 2B2 in open plating group.The length of incision,operation time,visual analog scale (VAS) 2 days after surgery,length of hospital stay,time of fracture healing,Constant score results of postoperative 6 months,1 year,and at the last follow-up,feedbacks on incision and functional satisfaction,and complications were compared between the two groups.Results The average follow-up was (19.6 ± 5.5)months in minimally invasive group and (20.3 ± 6.2)months in open plating group.The incision lengths of the minimally invasive group and the open plating group were (4.8 ±0.7)cm and (8.3 ± 1.6) cm,respectively.The minimally invasive group had significantly longer operation time [(75.5 ±21.6)minutes] compared with open plating group [(60.2 ± 19.1)minutes] (P <0.0l).In the minimally invasive group and open plating group,the VAS 2 days after surgery was (2.9 ± 1.5) points and (3.9 ± 1.7) points;the hospitalization time was (7.1 ± 2.6) days and (9.5 ± 2.9) days;the fracture healing time was (11.7 ± 2.2) weeks and (13.4 ± 2.9) weeks;patients' satisfaction with the appearance of the incision was 84% and 60%,respectively.There were no significant differences in the Constant score and functional satisfaction between the two groups at postoperative 6 months,l year,and the last follow-up (P > 0.05).The incidence of postoperative incisional hypertrophic scar was 8% and 30%,and the incidence of local skin numbness or sensory loss was 10% and 32% in minimally invasive group and open plating group,respectively (P < 0.0l).No significant differences in nonunion,internal fixation failure,incision infection,subcutaneous prominent plate or revision rate were found between the two groups (P > 0.05).Conclusion Percutaneous Kirschner wire assisted reduction with minimally invasive locking plate and open reduction with locking plate internal fixation can both achieve good clinical outcomes in the treatment of Robinson 2B midshaft clavicular fracture;but the former shows more advantages in terms of incision length,incision appearance,operation time,pain 2 days after surgery,fracture healing time,and local skin sensory disturbances.
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Objective@#To Evaluation the effect of PD-1 inhibitor Nivolumab on the proliferation and cytotoxicity of anti-CD19 chimeric antigen receptor T cells (CD19-CAR-T) in vitro.@*Methods@#Five patients with high PD-1 expression in peripheral blood and five healthy volunteers were selected. These peripheral blood mononuclear cells were used as the source of T cells to prepare CD19-CAR-T cells. Different doses (72, 36, 18 μg/ml) of Nivolumab was added on day 8 to the culture medium. Patient T cells incubated with 72 μg/ml Nivolumab and CD19-CAR-T cells of healthy volunteers were used as controls. CCK-8, lactate dehydrogenase (LDH) cytotoxicity assay and ELASA were used to detect the proliferation capacity, the specific cytotoxicity and the inflammatory factor secretion.@*Results@#①T cells from patients with high expression of PD-1 as the source of CD19-CAR-T cells did not affect transfection rate compared with that of healthy volunteers [(32.80±7.22)% vs (35.10±5.84)%, t=-0.554, P=0.593]. ②Incubation of CD19-CAR-T cells with 72 μg/ml Nivolumab did not affect CD19-CAR-T cell proliferation, but its cytotoxicity was significantly higher than that of CD19-CAR-T cells alone or patients’ T cells +72 μg/ml Nivolumab (all P<0.001), there was no significant difference in the killing activity between the 72 μg/ml and 36 μg/ml Nivolumab treated CD19-CAR-T cells on Pfeiffer cells (P=0.281, 0.267, respectively), and they were all higher than those of 18 μg/ml Nivolumab treated CD19-CAR-T cells (all P<0.001). ③Different doses of PD-1 inhibitor Nivolumab combined with CD19-CAR-T cells does not affect the secretion of IFN-γ and IFN-α (all P>0.05).@*Conclusion@#Combination of 36 μg/ml PD-1 inhibitor and CD19-CAR-T cells could reduce the drug toxicity and enhance the cytotoxicity.
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Objective To investigate the value of detecting peripheral blood epidermal growth factor receptor (EGFR) gene in predicting the therapeutic efficacy of advanced non-small cell lung cancer. Methods A total of 150 patients with stage ⅢA-Ⅳ non-small cell lung cancer diagnosed in Shanxi Provincial Cancer Hospital from October 2013 to February 2015 were collected. The peripheral blood EGFR gene was detected by amplification refractory mutation system (ARMS). The relationship between the mutation rate and the clinicopathological features of patients was observed, and 80 patients were selected into the follow-up treatment according to the inclusion criteria. Forty patients (all 19 or 21 exon mutations) in group A with EGFR gene mutation were treated with gefitinib orally. Forty patients with wild type EGFR gene in group B underwent 4 cycles of NP regimen. Efficacy and progression-free survival were evaluated in both groups. Results The mutation rate of EGFR gene was 33.3 % (50 cases), of which 29 were exon 19, 18 were exon 21 and 3 were exon 18 and 20. The mutation rate of EGFR gene was higher in female, adenocarcinoma and non-smoker (all P<0.05). Among the 80 patients who received follow-up treatment, the effective rate [67.5%(27/40) vs. 32.5 % (13/40)] and disease control rate [85.0 % (34/40) vs. 65.0 % (26/40)] in group A were significantly higher than those in group B, and the median PFS was prolonged (9.00 months vs. 4.25 months),the differences were statistically significant (χ2=9.800, P=0.002;χ2=4.267, P=0.039;χ2= 15.792, P<0.001). Conclusion The detection of peripheral blood EGFR mutation can be used to predict the efficacy of tyrosine kinase inhibitors in non-small cell lung cancer.
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AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
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Objective To analyse the serum levels and clinical significance of interleukin-8(IL-8),tumor necrosis factor-α(TNF-α)and high-sensitivity C-reactive protein(hs-CRP)in patients with acute cerebral infarction.Methods 40 cases of patients with a-cute cerebral infarction were enrolled in this study.The degrees of neurological impairment and infarct volumes of these patiens were evaluated,serum levels of IL-8,TNF-αand hs-CRP were detected as well.40 cases of healthy individuals were selected as con-trol.Results The serum levels of IL-8,TNF-αand hs-CRP in patients with acute cerebral infarction were higher than those in the control group,had statistically significant differences(P <0.05).The serum levels of IL-8,TNF-αand hs-CRP in these patients be-gan to rise at the onset of acute cerebral infarction and reached peak in 72 hours,were also correlated with the volumes of infarction and the degrees of neurologic impairment.14 days after onset of acute cerebral infarction,serum levels of these indexes returned to normal.Conclusion The serum levels of IL-8,TNF-α,hs-CRP are significantly elevated in the patients with acute cerebral infarc-tion,which may be correlated with the volumes of infarction and the degree of neurologic impairment,and could be used to guiding clinical treatment and estimating the severity and prognosis of acute cerebral infarction.
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Objective To observe the changes of serum 25‐hydroxy vitamin D[25‐(OH)D] level of patients with rheumatoid ar‐thritis(RA) and study its clinical significance .Methods The method of chemiluminescence was adopted to detect peripheral blood serum 25‐(OH) D of 60 cases of RA patients(RA group) and 60 cases of healthy people(control group) .Results The serum 25‐(OH) D level of patients in RA group was(34 .37 ± 8 .87) nmol/L ,while that of the control group was(61 .33 ± 7 .74) nmol/L ;after comparison ,the differences were statistically significant (t= -6 .892 ,P 0 .05) . Conclusion The serum 25‐(OH) D level of RA patients is significantly low ,which might be associated with the RA disease activi‐ty .
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2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
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Objective To explore the feasibility of human lung canccr cells grown in a decellularized rat lung matrix by perfusion.Methods Lungs were harvested from adult SD rats.Native cells of rat lungs were removed using 0.1% sodium dodecyl sulfate (SDS) and 1% Triton X-100 by perfusion to create a decellularized rat lung matrix.After decellularization,Human lung cancer H460 cells were implauted into the decellularized rat lung matrix and grown in a customized bioreactor with perfusion of oxygenated media for 1-2 weeks.Results Decellularized rat lung matrix showed preservation of matrix architecture devoid of all rat cells.H460 cells could grow in the bioreactor.Conclusions Human lung cancer H460 cells can grow in a customized bioreactor on a decellularized rat lung matrix.This ex vivo model can be used potentially to gain a deeper understanding of the biologic processes involved in human lung cancer.
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Objective To study the relationship between small Y and azoospermia factor (AZF)microdeletions and the effect on male infertility.Methods Data of 379 infertile males of chromosomal karyotype analysis from May 2010 to October 2011 were investigated.Patients with small Y chromosome were also performed C banding and AZF microdeletions,and their fathers and brothers were offered the same examinations.Results Eight patients were small Y chromosome,and their fathers or brothers' chromosome karyotypes were consistent with the probands.Among the 8 cases,there were 3 patients with AZF microdeletions,while their fathers and brothers didn't have microdeletions.Another 5 cases of small Y and their fathers did not exist AZF microdeletions.Conclusions The small Y karyotype is not the key factors that cause male infertility.The reason for infertile patients with small Y and AZF microdeletions was maybe the microdeletions.However,patients with small Y but without AZF microdeletions are not important to male infertility.
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To obtain a better understanding of the progression of atherosclerosis and identify potential biomarkers, proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabonomics was used to study the metabolic changes in the plasma of hamster fed with a high-fat/cholesterol diet. Plasma samples were collected at different time points during the progression of atherosclerosis and individual proton NMR spectra were visually and statistically assessed using multivariate analyses. NMR results for all samples showed a time-dependent development from physiological to pathophysiological status during atherosclerosis. Analysis of the identified biomarkers of atherosclerosis suggests that lipid and amino acid metabolisms are significantly disturbed, together with inflammation, oxidative stress, following cholesterol overloading. The results enriched our understanding of the mechanism of atherosclerosis and demonstrated the effectiveness of the NMR-based metabonomics approach to study such a complex disease.
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The goal of treatment of metabolic syndrome is the prevention of diabetes and cardiovascular events. A series of novel tetrahydrocoptisine quaternary ammonium compounds were prepared to evaluate their action of hypoglycemia and hypolipidemia for finding the therapeutic agents of metabolic syndrome. Starting from the coptisine hydrochloride (2), fifteen target compounds were synthesized by reduction and substitution of the 7-N position. All of the target compounds were characterized by 1H NMR and HR-MS. Their hypoglycemic activities were evaluated in HepG2 cell and hypolipidemic activities of compounds with better hypoglycemic activity were tested further in vivo. Results indicated that compounds 5, 7, 8 and 9 exhibited better hypoglycemic activities in vitro and compounds 5 and 8 exhibited good hypolipidemic activities in high-fat-diet (HFD) induced hyperlipidemia mice and (or) hamsters. However, the activity is not as good as simvastatin.
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BACKGROUND: Measuring the slope of proximal tibiofibular joint may elucidate the anatomical structure and type of proximal tibiofibular joint, and evaluate the stability of proximal tibiofibular joint. OBJECTIVE: To investigate the measurement methods and clinical significance of the joint slope by comparing the slope measurement of bilateral proximal tibiofibular joint surface on X-ray and 64-row spiral CT reconstruction.METHODS: One hundred normal adult volunteers, including 50 males and 50 females, aged 18-90 years, were photographed in double knees via internal rotation to 30°, 45° and 60°, respectively and scanned with 64-row spiral CT, tibiofibular bone (including knee joints) was reconstructed. The included angle between proximal tibiofibular articular surface and the longitudinal axis of the fibula shaft, between the proximal tibiofibular articular surface and the horizontal line, were measured using an angle square.RESULTS AND CONCLUSION: There were great variations of the data in the same proximal tibiofibular joint measured by X-ray and spiral CT. X-ray results are affected by the site of photograph position, and the slope of articular surface is estimated, so the 64-row spiral CT is an accurate and convenient method to reconstitute the slope of proximal tibiofibular joints. Spiral CT could be used to distinguish the dislocation and instability of the proximal tibiofibular joint, accordingly reduce the clinical misdiagnosis.
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To establish a highly sensitive and specific method to detect the presence of Cryptosporidium homini, the RT-PCR-ELISA assay was tried, in which the primer with a biotin-labeled probe was designed to amplify fragment containing the highly variable region by multiple alignment between p23 gene of C.hominis and other Cryptosporidium spp. The RT-PCR was used to amplify the target fragment, and the amplified product was used to hybridize with the probe primer. The hybridized product was then captured on micro-plate wells coated with streptavidin and reacted with anti-digoxin antibody labeled with horse-radish peroxidase. This method of testing was then used for the detection of C.hominis in 22 clinical specimens and compared with the conventional methods of testing. It was demonstrated that the RT-PCR--ELISA for the detection of C.hominis was proved to be quite sensitive and specific. Its sensitivity was 100 times higher than that of the general PCR. From the result of clinic detection, the detection rate of RT-PCR-ELISA assay attained to 86%(19/22), while those of RT-PCR, sucrose floating method and anti-acid staining were 27%, 27% and 50% respectively. This result indicates that the RT-PCR-ELISA assay is more sensitive to detect C.hominis than the other three methods of testing.
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Objective To investigate the etiology and treatment of iatrogenic ureteral injury(IUI) and bladder injury(IBI). Methods Forty-seven patients(7 males, 40 females) with ureteral and bladder inju-ries caused as a result of any medical procedures were reviewed from 1996 to 2007. Obstetrics and gynecolog-ical, urological,general surgical procedures were involved in 38, 6, and 4 of the injuries respectively. Re-sults Sixteen cases of IUI were found during operation, including 14 cases of entire ureteral laceration, 4 cases of partial ureteral laceration. Thirteen cases received ureteral anastomosis, one case received uretero-neopyelostomy. One case of ureteral perforations during ureteroscopic procedure was indweUed of double-J after the operation was terminated immediately. Three cases received nephrectomy. Four cases of lower ure-teric suture ligation and three cases of ureterovaginal fistula were detected at 3 days~ one week of postopera-tion. These 7 cases were received ureteroneocystomy during 2 weeks after the initial surgical procedure. Nineteen cases of IBI were found during operation, the length of cystic wound was ranging from 1 cm to 3 cm. 17 cases underwent repairing, 2 eases of bladder perforation which caused by endourologic or TVT procedure received catheterization for 1 week. Five cases of vesicovaginal fistula which were found during one week--one month of post-operation, were received fistula resection and bladder repairing 3 months after of initial operation. Forty-seven cases were follow-up ranging from 5 months to 11 years after the second opera-tion,mean time were 47 months. All cases were recovered. Conclusions Intraoperative findings and effec-tive treatments can achieve good therapeutic effects and avoid injury during secondary operation. Correct treatment of urinary fistula can promote cure rate.
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@#ObjectiveTo assess the effects of crude extract of Cape Jasmine in the experimental Alzheimer's model induced by Aβ25-35 and the memory acquisition impaied model induced by ibotenic acid(IBO).MethodsAlzheimer's dementia of mice was induced by Aβ25-35 i.cv. treatment and the impaired memory acquisition model was induced by IBO injected into the forebrain nucleus basalis. The effects of crude extract of Cape Jasmine on the learning and memory function of model animals were evaluated with Morris water maze and step-through test in 3 dose groups(12-5, 25, 50 mg/kg). Donepezil(0-75 mg/kg)was used in the positive control group.ResultsMorris water maze test showed that the spatial learning and memory ability of the model mice significantly improved in three crude extract of Cape Jasmine groups(P<0-05). Meanwhile, the impaired function of the rats induced by IBO significantly improved in the medium dose group(P<0-01). The electric shock latent period in step-through box test prolonged and the frequency of electric shock decreased within 3 minutes in three groups.ConclusionCrude extract of Cape Jasmine can improve the learning and memory function of mice or rat in the model group.
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Objective To study the clinical efficacy and operative skill of multi-endoscopic technique in treatment of post-traumatic urethrostenosis in male patients.Methods A retrospective analysis was done on clinical data of 47 male patients with post-traumatic urethrostenosis treated with direct visional incision urethrotomy combined with transurethral resection of scar tissue and ureteroscopic incision.There were 29 patients with anterior urethral strictures and 18 with posterior urethral strictures.Results Of all,43 patients underwent successful endoscopic surgeries at the first time but one underwent secondary surgery because of unsuccessful endoscopic incision.These patients achieved satisfactory results without urinary incontinence,fistula or reoperation.The left three patients underwent open surgeries because of unsuccessful endoscopic incision,in which one patient could micturate at maximal flow rate of 9-12 ml/s,without therapeutic urethral dilation,one could micturate under regular therapeutic dilation and the other one could not micturate.Conclusions With the advantages of safety,high success rate and good long-term efficiency,multi-endoscopic technique can be used as an initial treatment for male patients with post-traumatic urethrostenosis and is worthy to be popularized.