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1.
Article in Chinese | WPRIM | ID: wpr-939678

ABSTRACT

OBJECTIVE@#To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance.@*METHODS@#Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot.@*RESULTS@#The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001).@*CONCLUSION@#AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.


Subject(s)
Cell Line , Cytarabine/pharmacology , Drug Resistance , Humans , Leukemia, Myeloid, Acute/genetics , RNA, Messenger/genetics , Sirtuin 1
2.
Frontiers of Medicine ; (4): 240-250, 2022.
Article in English | WPRIM | ID: wpr-929208

ABSTRACT

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.


Subject(s)
Animals , High-Throughput Nucleotide Sequencing , Humans , Methylation , Mice , MicroRNAs/genetics , Oxidative Stress , RNA, Small Interfering/metabolism , Real-Time Polymerase Chain Reaction
3.
Article in Chinese | WPRIM | ID: wpr-879552

ABSTRACT

OBJECTIVE@#To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency.@*METHODS@#Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS).@*RESULTS@#Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father.@*CONCLUSION@#CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.


Subject(s)
Carnitine/blood , Carnitine O-Palmitoyltransferase/genetics , Child , DNA Mutational Analysis , Female , Humans , Hypoglycemia/genetics , Lipid Metabolism, Inborn Errors/genetics
4.
Article in Chinese | WPRIM | ID: wpr-878922

ABSTRACT

Polygonum multiflorum is a traditional Chinese herbal medicine and has many biological activities such as hair-blacking, anti-atherosclerosis, anti-inflammatory and anti-aging. However, the liver injury induced by P. multiflorum has aroused wide attention in recent years. 2,3,5,4'-tetrahydroxystibane-2-O-β-D-glucoside(TSG) is a main component of P. multiflorum, but the role of TSG in inducing liver injury is unclear. The aim of present study was to evaluate TSG's potential liver injury and effects on bile acid homeostasis and phospholipids efflux. C57 BL/6 J mice received intraperitoneal administration of 400 mg·kg~(-1) of TSG daily for 15 days, and then biochemical indexes of liver injury and changes of phospholipid content were detected. The changes of bile acid compositions were detected by LC-MS/MS. The results showed TSG 400 mg·kg~(-1) significantly increased the content of serum total bile acid(TBA) and alkaline phosphatase(ALP). Elevated free bile acid levels were observed in TSG-treated groups, including β-muricholic acid(β-MCA), ursodeoxycholic acid(UDCA), hyodeoxycholic acid(HDCA), chenodeoxycholic acid(CDCA), deoxcholic acid(DCA) in serum and β-MCA, CDCA in liver. TSG inhibited the protein expression of farnesoid X receptor(FXR) and down stream bile salt export pump(BSEP), which may result in the accumulation of bile acid. TSG also inhibited the expression of 25-hydroxycholesterol-7 alpha-hydroxylase(CYP7 B1), which may disturb the alternative pathway for bile acid synthesis. In addition, intraperitoneal injection of TSG 400 mg·kg~(-1) significantly decreased the content of phospholipids in bile. The research showed that TSG significantly inhibited the expression of multidrug resistance protein 2(MDR2) and destroyed the regular distribution of MDR2 on the bile duct membrane of liver. In vitro results showed that the IC_(50) of TSG on HepG2 cells was about 1 500 μmol·L~(-1) and TSG at 500 μmol·L~(-1)(for 24 h) could destroy the distribution of MDR2 on the bile duct membrane of liver. In conclusion, TSG induced liver injury by disrupting bile acid homeostasis and phospholipids efflux.


Subject(s)
Animals , Bile Acids and Salts , Chromatography, Liquid , Glucosides , Homeostasis , Liver , Mice , Phospholipids , Tandem Mass Spectrometry
5.
Article in English | WPRIM | ID: wpr-881062

ABSTRACT

Triptolide (TP), an active component of Tripterygium wilfordiiHook. f. (TWHF), has been widely used for centuries as a traditional Chinese medicine. However, the clinical application of TP has been restricted due to multitarget toxicity, such as hepatotoxicity. In this study, 28 days of oral TP administration (100, 200, or 400 μg·kg

6.
Article in Chinese | WPRIM | ID: wpr-883559

ABSTRACT

Objective:To explore and optimize the teaching content of clinical case discussion course based on clinical pathophysiology and therapy (CPPT), and to improve the teaching quality of this course.Methods:Self-compiled evaluation form was sent to all the students who participated in this course in 2016-2017 school year, and the teaching satisfaction and teaching characteristics were evaluated. The differences of evaluation results from students with different educational programs or teachers with different seniority were compared, and the correlation between evaluation results and teachers' seniority was analyzed.Results:The students had a high evaluation on the course, but students from different programs had significant different comments on thinking inspiring, speech encouraging, questions guiding, process holding and effective feedback, as well as the self-evaluation of mastery degree. For teachers with different seniority, there were significant differences in scores in all aspects except speech encouraging, but no differences in mastery degree. Spearman analysis showed that there was a certain correlation between scores and teachers' seniority.Conclusion:The overall situation of the CPPT case discussion course in our school is worthy of recognition, but it needs to be improved in many aspects.

7.
Article in English | WPRIM | ID: wpr-922758

ABSTRACT

Tripterygium wilfordii multiglycoside (GTW) is a commonly used compound for the treatment of rheumatoid arthritis (RA) and immune diseases in clinical practice. However, it can induce liver injury and the mechanism of hepatotoxicity is still not clear. This study was designed to investigate GTW-induced hepatotoxicity in zebrafish larvae and explore the mechanism involved. The 72 hpf (hours post fertilization) zebrafish larvae were administered with different concentrations of GTW for three days and their mortality, malformation rate, morphological changes in the liver, transaminase levels, and histopathological changes in the liver of zebrafish larvae were detected. The reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the levels of microRNA-122 (miR-122) and genes related to inflammation, apoptosis, cell proliferation and liver function. The results showed that GTW increased the mortality of zebrafish larvae, while significant malformations and liver damage occurred. The main manifestations were elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), significant liver atrophy, vacuoles in liver tissue, sparse cytoplasm, and unclear hepatocyte contours. RT-PCR results showed that the expression of miR-122 significantly decreased by GTW; the mRNA levels of inflammation-related genes il1β, il6, tnfα, il10, cox2 and ptges significantly increased; the mRNA level of tgfβ significantly decreased; the mRNA levels of apoptosis-related genes, caspase-8 and caspase-9, significantly increased; the mRNA level of bcl2 significantly decreased; the mRNA levels of cell proliferation-related genes, top2α and uhrf1, significantly reduced; the mRNA levels of liver function-related genes, alr and cyp3c1, significantly increased; and the mRNA level of cyp3a65 significantly decreased. In zebrafish, GTW can cause increased inflammation, enhanced apoptosis, decreased cell proliferation, and abnormal expression of liver function-related genes, leading to abnormal liver structure and function and resulting in hepatotoxicity.


Subject(s)
Animals , Apoptosis , Chemical and Drug Induced Liver Injury/genetics , Inflammation/genetics , Trans-Activators , Tripterygium , Zebrafish/genetics , Zebrafish Proteins
8.
Article in Chinese | WPRIM | ID: wpr-908803

ABSTRACT

Objective:To explore the application value of wide detector multi-slice spiral CT target scanning technique in the preoperative evaluation of pancreatic cancer.Methods:The clinical data of 22 patients with pancreatic cancer who underwent pancreatic arterial contrast enhanced CT scanning and were diagnosed by pathology in the First Affiliated Hospital of Naval Medical University from September 2019 to October 2019 were analyzed retrospectively. The CT phantom experiment was carried out on the international standard phantom CATPHON500. By changing the scanning radiation dose, scanning mode and scanning field of view, the spatial resolution and density resolution of the image were compared and analyzed. The target scan technical parameters obtained from the experiment were applied to the late arterial phase of MDCT enhanced scan in 22 patients with pancreatic cancer. Executive current, volume scanning mode and small scanning field were used for scanning. The attenuation value (CT value) and noise value (SD value) of pancreatic cancer tissue and normal pancreatic tissue were measured at different phases, the attenuation difference and contrast signal-to-noise ratio (CNR) of the two tissues were calculated, the contrast difference between the two tissues was evaluated, and the CT values of celiac trunk, renal artery and vein, superior mesenteric artery and vein, splenic vein and portal vein were measured, and the display of tumor tissue and peripancreatic important vessels was evaluated.Results:In the phantom experiment, under the condition of the same radiation dose, the image quality of the volume scan mode was better than that of the spiral scan mode (1%@4 mm versus 1%@9 mm at 5 mGy and 1%@2 mm versus 1%@6 mm at 25 mGy). In comparison between pancreatic tumor and pancreatic tissue, the enhancement process of pancreatic tumor tissue was increased at first and then decreased, while that of pancreatic tumor tissue was slightly enhanced. The attenuation difference between pancreatic tissue and tumor tissue and CNR also increased at first and then decreased, reaching the maximum at the late arterial stage [(91.96±29.29)HU, 8.60±5.71]. The differences between each phase were statistically significant ( F values were 47.20 and 19.80 respectively, all P values <0.05). The evaluation of vascular variation and invasion showed that a better arterial phase image could be obtained on the late arterial target scan images, while taking into account the display of splenic vein, mesenteric vein and portal vein. Conclusions:The wide detector MDCT target scanning technique can improve the spatial resolution and density resolution of the image, greatly improve the contrast between tumor tissue and peripancreatic tissue and blood vessels, and provide more accurate tumor staging and resectability evaluation information for preoperative evaluation of pancreatic cancer.

9.
Article in Chinese | WPRIM | ID: wpr-828263

ABSTRACT

OBJECTIVE@#To introduce the technical key points of lumbar annulus fibrosus suture under full-endoscope and analyze the clinical efficacy of full-endoscopic lumbar discectomy and annulus fibrosus suture.@*METHODS@#A total of 50 patients with non contained lumbar disc herniation treated with full-endoscopic lumbar discectomy and annulus fibrosus suture in our department between January 2018 and November 2018 were included. Full-endoscopic single-stitch suture through transforaminal approach or double-stitch suture through interlaminar approach was selected according to lesion level. The lumbar MRI and CT were reexamined on the second day and 3 months after surgery to evaluate the completeness of the discectomy and the adequacy of nerve decompression respectively. The patients were followed up on the second day, 3 months, 6 months, and 1 year after surgery for pain relief using visual analogue scale (VAS, 100 -point scale). The patients were followed up at 3 months, 6 months, and 1 year postoperatively for the recovery of lumbar spine function using Oswestry Disability Index(ODI). At the 1-year follow-up, the Macnab standard of lumbar spine function was evaluated, and the recovery of nerve root function (sensory, muscular and reflex) was recorded.@*RESULTS@#All operations were successfully completed, of which 27 patients were treated with transforaminal approach(including 8 cases of L and 19 cases of L), and 23 patients(including 11 cases of L and 12 cases of LS) with interlaminar approach. The average operation time was 43.2 minutes. There were no surgical complications and no recurrence of lumbar disc herniation. Postoperative lumbar MRI and CT examinations of all patients showed that the herniated disc was completely removed and the nerveswere fully decompressed. All patients had significant relief of low back pain and lower extremity radiation pain, and the ODI score improved significantly(0.05).@*CONCLUSION@#Full-endoscopic lumbar discectomy and annulus fibrosus suture are safe and effective techniques for minimally invasive spinal surgery, which can reduce the recurrence rate of lumbar disc herniation after full endoscopic lumbar discectomy.


Subject(s)
Annulus Fibrosus , Diskectomy, Percutaneous , Endoscopy , Humans , Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Lumbar Vertebrae , Retrospective Studies , Sutures , Treatment Outcome
10.
Article in Chinese | WPRIM | ID: wpr-828067

ABSTRACT

This study aimed to investigate whether psoralen can aggravate hepatotoxicity induced by carbon tetrachloride(CCl_4) by inducing hepatocyte cycle arrest and delaying liver regeneration. Female C57 BL/6 mice aged 6-8 weeks were randomly divided into control group, model group(CCl_4 group), combined group(CCl_4+PSO group) and psoralen group(PSO group). CCl_4 group and CCl_4+PSO group were given CCl_4 intraperitoneally at a dose of 100 μL·kg~(-1) once; olive oil of the same volume was given to control group and PSO group intraperitoneally; 12 h, 36 h and 60 h after CCl_4 injection, PSO group and CCl_4+PSO group were administrated with PSO intragastrically at a dose of 200 mg·kg~(-1); 0.5% CMC-Na of the same volume was administrated to control group and PSO group intragastrically. The weight of mice was recorded every day. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured at 36 h, 60 h and 84 h after CCl_4 injection. Mice were sacrificed after collection of the last serum samples. Liver samples were collected, and liver weight was recorded. Histopathological and morphological changes of liver were observed by haematoxylin and eosin staining. The mRNA levels of HGF, TGF-β, TNF-α, p53 and p21 in liver were detected by RT-qPCR. Western blot was used to detect the levels of cell cycle-related proteins. According to the results, significant increase of serum ALT and AST and centrilobular necrosis with massive inflammatory cell infiltration were observed in CCl_4+PSO group. After PSO administration in CCl_4 model, the mRNA levels of HGF(hepatocyte growth factor) and TNF-α were reduced, while the mRNA expressions of TGF-β, p53 and p21 was up-regulated. The expression of PCNA(proliferating cell nuclear antigen) was significantly increased in CCl_4 and CCl_4+PSO group, while the relative protein level in CCl_4+PSO group was slightly lower than that in CCl_4 group. Compared with control and CCl_4 group, the expression of p27(cyclic dependent kinase inhibitor protein p27) was prominently increased in CCl_4+PSO group. These results indicated that hepatotoxicity induced by CCl_4 could be aggravated by intraperitoneal administration with PSO, and the repair process of liver could be delayed. The preliminary mechanism may be related to the inhibition of PCNA and regulation of some cell cycle-associated protein by psoralen, in which the significant up-regulation of p27, p53 and p21 may play important roles.


Subject(s)
Alanine Transaminase , Animals , Aspartate Aminotransferases , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Female , Ficusin , Liver , Liver Regeneration , Mice
11.
Article in Chinese | WPRIM | ID: wpr-846449

ABSTRACT

Objective: To investigate the flavonoids and lignans from the flowers of Stellera chamaejasme and their structure-activity relationship (SAR) of antioxidant activity. Methods: The compounds were isolated by column chromatography and HPLC packed with macroporous resin, silica gel, and Sephadex LH-20. Their structures were elucidated by spectroscopic analysis. Their anti-oxidant activities in vitro were evaluated by DPPH, ABTS, and FRAP assays. Results: Twelve compounds were isolated from the flowers of S. chamaejasme, and identified as artemisetin (1), quercetin (2), isoscutellarein-8-O-β-D-glucuronopyranoside (3), quercetin-3-O-β-D- glucopyranoside (4), astragalin (5), hypolaetin-8-O-β-D-glucuronopyranoside (6), kaempferol 3-O-β-D-glucopyranosyl-(1→2)-O-α- L-xylopyranoside (7), rel-(3R,3'S,4R,4'S)-3,3',4,4'-tetrahydro-6,6'-dimethoxy [3,3'-bi-2H-benzopyran]-4,4'-diol (8), matairesinol (9), uralenol (10), cycloastragenol (11), and (+)-pinoresinol (12). Conclusion: Compounds 1, 3, 5-7, and 10 are isolated from this plant for the first time, and compounds 2, 4, 5, and 10 showed significant antioxidant activity, and the SAR analysis suggested that the glycosylation at the C-8 or C-3 position of flavonoids could weaken their antioxidant activity.

12.
Article in Chinese | WPRIM | ID: wpr-870709

ABSTRACT

Objective:To investigate the risk factors of bleeding events in patients with high international normalized ratio (INR) values (INR>3.5) in warfarin therapy.Methods:Two hundred and one patients with high INR values (INR>3.5) during warfarin therapy admitted in Beijing Tongren Hospital from August 2013 to August 2019 were enrolled. The bleeding occurred in 75 patients (bleeding group) and did not occur in 126 cases (non-bleeding group) during hospitalization. The bleeding group included 12 major bleeding patients and 63 minor bleeding patients. The baseline information, laboratory results and medication of other drugs were recorded.Results:There were no significant differences in age, sex, smoking history, drinking history, previous bleeding history and the proportion of first application of warfarin between the two groups ( P>0.05).The proportion of patients with liver dysfunction [7.14%(9/126)], renal dysfunction [11.90%(15/126)], anemia [4.76%(6/126)], hypoproteinemia [4.76%(6/126)], infectious diseases [20.63%(26/126)] in non-bleeding group were significantly lower than that in bleeding group [16.00% (12/75), 32.00% (24/75), 29.33%(22/75), 16.00%(12/75), 44.00%(33/75); χ 2=3.942, 12.140, 23.675, 7.283, 12.377, respectively; all P<0.05]. A total of 54 kinds of drugs were associated with the INR elevation. The most commonly used drugs were cardiovascular system drugs ( n=162, 80.60%), blood system drugs ( n=155, 77.11%), anti-infective drugs ( n=112, 55.72%), digestive system drugs ( n=82, 40.80%), and endocrine system drugs ( n=56, 27.86%). The INR values [4.58(3.94, 5.90), 4.96(4.03, 8.27)] and the HAS-BLED scores [3.00 (2.00,3.00), 3.00(2.25,3.00)] in minor bleeding group ( n=63) and major bleeding group ( n=12) were higher than those in non-bleeding group [4.00(3.74, 4.35), 2.00 (1.00,3.00), P<0.01), but there was no significant difference in INR values and HAS-BLED scores between minor bleeding group and major bleeding group ( P>0.05). Conclusion:There are many factors leading to the increase of INR in patients taking warfarin, such as abnormal liver and kidney function, anemia, hypoproteinemia, and the use of antibacterial drugs. It is necessary to be cautious about co-administration in these patients.

13.
Article in Chinese | WPRIM | ID: wpr-868870

ABSTRACT

Objective:To study the occurrence and disappearance of gallbladder polyps in patients who underwent multiple ultrasonographic examinations, and to determine the risk factors of formation of gallbladder polyps.Methods:From January 2014 to December 2017, relevant data on patients who underwent follow-up abdominal ultrasound examinations at the Health Screening Center of Xuanwu Hospital was retrospectively analyzed, and the dynamic changes of gallbladder polyps were assessed. A comparative analysis was then conducted between those who had gallbladder polyps (the gallbladder polyps group, n=1 149) and those who had no gallbladder polyps (the control group, n=18 243). The occurrence, changes and disappearance of gallbladder polyps shown on multiple untrasonographic examinations were compared. Results:The patterns of changes of gallbladder polyps showed that the proportions of patients with gallbladder polyps which were stable in size ( n=1 149, 52.1%) were greater than those who had new appearance of gallbladder polyps ( n=797, 36.2%), and these 2 groups of patients were having higher proportions than those who had disappearance of gallbladder polyps ( n=258, 11.7%). The largest proportion of gallbladder polyps were found in middle-aged people, and new polyps were mainly found in the age group of 30.0-59.0 years. The peak of gallbladder polyps incidence was after age 60. There were significant differences in age, male, blood glucose, total cholesterol, low density lipoprotein (LDL), and diastolic blood pressure between the study and the control groups (all P<0.05). Multivariate analysis showed that age ( OR=1.152), male ( OR=1.407) and LDL ( OR=1.656) were independent risk factors of gallbladder polyp formation. Conclusions:The annual incidence of gallbladder polyps was 9.7‰. Gallbladder polyps were more commonly found in middle age, and the incidence of gallbladder polyps was increasing. Gallbladder polyps could disappear. However, with increase in initial diameter of gallbladder polyps, the probability of disappearance decreased. Age, male gender and elevated LDL were independent risk factors of gallbladder polyps formation.

14.
Article in Chinese | WPRIM | ID: wpr-843260

ABSTRACT

Objective:To establish a lung cancer mouse model with humanized peripheral blood mononuclear cells (PBMC) expressing programmed death-ligand 1 (PD-L1), and study the role of the model in evaluating the efficacy of programmed death-1 (PD-1) inhibitors. Methods:Fresh biopsy tissue samples or tumor cells in malignant pleural effusion from the patients with advanced non-small cell lung cancer were inoculated subcutaneously in CB17-SCID mice to establish patient-derived xenograft (PDX) models. The expression of PD-L1 in PDX models was detected by immunohistochemistry. The mature human PBMC and PDX model tumor cells were mixed and then inoculated into NCG mice to establish a PDX model of lung cancer with humanized immunity, on which the efficacy of PD-1 inhibitor was verified. Results:Among the PDX models established by 16 clinical samples, 2 were strongly positive for PD-L1, 4 were positive, and the rest were negative. In the PDX model with strongly positive PD-L1, the tumor growth inhibition rate of cindilimab, an inhibitor of PD-1, was 82.6%, 21 days after the initial administration; in the PDX model with negative PD-L1, the inhibitor of PD-1 showed no antitumor activity. Conclusion:A PD-L1-expressing lung cancer mouse model with humanized immunity is successfully established and the efficacy of PD-1 inhibitor can be evaluated on the model.

15.
Article in Chinese | WPRIM | ID: wpr-775937

ABSTRACT

OBJECTIVE@#To analyze the effects of intradermal needling for pain and tear film stability in patients after pterygium excision.@*METHODS@#A total of 76 patients (98 affected eyes) with primary pterygium were randomly divided into an observation group (38 cases, 53 affected eyes) and a control group (38 cases, 45 affected eyes).In the control group, only pterygium resection was performed, in the observation group, intradermal needling after pterygium resection was applied at Cuanzhu (BL 2), Yuyao (EX-HN 4), Taiyang (EX-HN 5), Sibai (ST 2), Hegu (LI 4), removed after 24 h and changed three times a week. The pain level of 3 days after surgery, dry eye symptoms, the basic tear secretion test (Schirmer-Ⅰ), and the tear-break time (BUT) changes before surgery, 2 weeks after surgery and 4 weeks after surgery were compared between the two groups, and the clinical efficacy was evaluated.@*RESULTS@#The pain level of 3 days after surgery in the observation group was significantly lower than that in the control group (<0.05). The dry eye symptom scores at 2 weeks and 4 weeks after surgery in the two groups were significantly lower than those before surgery (all <0.05), and the dry eye symptom scores in the observation group were significantly lower than those in the control group (both <0.05). The Schirmer-Ⅰ test at 2 weeks and 4 weeks after surgery was significantly prolonged than that before surgery(all <0.05), and the Schirmer-Ⅰ test in the observation group was significantly longer than that in the control group (both <0.05). The BUT at 2 weeks and 4 weeks after surgery in the two groups was significantly longer than that before surgery (all <0.05), and the BUT in the observation group was significantly longer than that in the control group (both <0.05). The total effective rate in the observation group was 89.5% (34/38), which was higher than 71.1% (27/38) in the control group (<0.05).@*CONCLUSION@#Intradermal needling can effectively reduce the pain level of patients after pterygium resection, improve dry eye symptoms, promote the secretion of tears and improve the tear film stability.


Subject(s)
Acupuncture Points , Dry Eye Syndromes , Humans , Pain , Pterygium , Tears
16.
Chinese Journal of Lung Cancer ; (12): 336-340, 2019.
Article in Chinese | WPRIM | ID: wpr-775623

ABSTRACT

BACKGROUND@#The detection of pulmonary nodules is a key step to achieving the early diagnosis and therapy of lung cancer. Deep learning based Artificial intelligence (AI) presents as the state of the art in the area of nodule detection, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the performance of AI in the detection of malignant and non-calcified nodules in chest CT.@*METHODS@#Two hundred chest computed tomography (CT) data were randomly selected from a self-built nodule database from Tianjin Medical University General Hospital. Both the pathology confirmed lung cancers and the nodules in the process of follow-up were included. All CTs were processed by AI and the results were compared with that of radiologists retrieved from the original medical reports. The ground truths were further determined by two experienced radiologists. The size and characteristics of the nodules were evaluated as well. The sensitivity and false positive rate were used to evaluate the effectiveness of AI and radiologists in detecting nodules. The McNemar test was used to determine whether there was a significant difference.@*RESULTS@#A total of 889 non-calcified nodules were determined by experts on chest CT, including 133 lung cancers. Of them, 442 nodules were less than 5 mm. The cancer detection rates of AI and radiologists are 100%. The sensitivity of AI on nodule detection was significantly higher than that of radiologists (99.1% vs 43%, P<0.001). The false-positive rate of AI was 4.9 per CT and decreased to 1.5 when nodules less than 5 mm were excluded.@*CONCLUSIONS@#AI achieves the detection of all malignancies and improve the sensitivity of pulmonary nodules detection beyond radiologists, with a low false positive rate after excluding small nodules.


Subject(s)
Artificial Intelligence , Deep Learning , Humans , Lung Neoplasms , Diagnosis , Diagnostic Imaging , Multiple Pulmonary Nodules , Diagnosis , Diagnostic Imaging , Tomography, X-Ray Computed
17.
Article in Chinese | WPRIM | ID: wpr-773714

ABSTRACT

Triptolide( TP) is isolated from the traditional Chinese medicine Tripterygium wilfordii,which exhibits notable immuneregulative effect. Th17 cells involve in inflammatory response and Treg cells contribute to immune tolerance. They both play an important role in immune response. Previous studies have investigated that TP induced hepatic Th17/Treg imbalance. However,the effect of TP on spleen Th17/Treg cells remains unclear. Therefore,the aim of present study was to investigate the effect of TP on Th17/Treg cells in spleen. In this study,the effect of TP on the proliferation of splenic lymphocyte was detected by cytotoxicity test in vitro. After different concentrations of TP( 2. 5,5,20,40 nmol·L~(-1)) were given to splenic lymphocyte,cytokines secreted from the supernatant of splenic lymphocyte were detected by cytometric bead array,and the expression of suppressor of cytokine signaling( SOCS) mRNA was detected by qRT-PCR. Female C57 BL/6 mice were continuously observed for 24 h after treatment of 500 μg·kg-1 TP. The effects of TP on the splenic tissue structure and the percentage of Th17/Treg cells were examined. The results showed that the IC50 of TP was19. 6 nmol·L~(-1) in spleen lymphocytes. TP inhibited the secretion of IL-2 and IL-10 and induced the expression of SOCS-1/3 mRNA in spleen lymphocytes at the dosage of 2. 5 and 5 nmol·L~(-1) after 24 h in vitro. Administration of TP at dosage of 500 μg·kg-1 had no significant spleen toxicity in vivo. TP treatment increased the percentage of Th17 cells after 12 h and inhibited the proportion of Treg cells after 12 and 24 h. In conclusion,TP reduced the secretion of IL-2 and IL-10 through SOCS-1/3 signaling pathway,thereby induced the percentage of Th17 cells and inhibited the percentage of Treg cells.


Subject(s)
Animals , Cytokines , Metabolism , Diterpenes , Pharmacology , Epoxy Compounds , Pharmacology , Female , Mice , Mice, Inbred C57BL , Phenanthrenes , Pharmacology , Signal Transduction , Spleen , Cell Biology , Suppressor of Cytokine Signaling 1 Protein , Metabolism , Suppressor of Cytokine Signaling 3 Protein , Metabolism , T-Lymphocytes, Regulatory , Cell Biology , Th17 Cells , Cell Biology
18.
Article in Chinese | WPRIM | ID: wpr-773707

ABSTRACT

Traditional Chinese medicine Tripterygium wilfordii Hook.f( TWHF) is a natural botanical drug in China. It has complex chemical compositions and has been used for a long history. TWHF was used as an insecticide to protect crops at early stage,and it was later found to have significant effects in the treatment of rheumatoid arthritis,attaining great concerns. With further researches,it was found that TWHF can treat various diseases in the medical field due to a variety of pharmacological activities such as anti-cancer,neuroprotection,anti-inflammatory and immune-suppressing,particularly. Multiple extracts of TWHF have unique immunosuppressive function,playing an immune role through multi-target and multi-channel,with significant effect in the treatment of autoimmune diseases. As an immune-suppressing drug,TWHF is worthy of in-depth research due to its broad application prospects. While achieving good clinical efficacy,reports about its toxic effects to multiple systems of the body are also increasing,greatly hindering its clinical application. In order to fully understand the immune-suppressing function of TWHF and reduce or avoid the occurrence of toxic and side effects,we summarized recent progress of TWHF on the immune organs,cells and factors in recent years,as well as the pharmacology and toxic effects,hoping to provide a scientific and reasonable reference for its wider use in clinical treatment.


Subject(s)
Arthritis, Rheumatoid , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Humans , Immune System , Plant Extracts , Pharmacology , Tripterygium , Chemistry
19.
Article in Chinese | WPRIM | ID: wpr-773694

ABSTRACT

Tripterygium wilfordii multiglycoside( GTW),an extract derived from T. wilfordii,has been used for rheumatoid arthritis and other immune diseases in China. However its potential hepatotoxicity has not been investigated completely. Firstly,the content of triptolid( TP) in GTW was 0. 008% confirmed by a LC method. Then after oral administration of GTW( 100,150 mg·kg-1) and TP( 12 μg·kg-1) in female Wistar rats for 24 h,it was found that 150 mg·kg-1 GTW showed more serious acute liver injury than 12 μg·kg-1 TP,with the significantly increased lever of serum ALT,AST,TBA,TBi L,TG and bile duct hyperplasia even hepatocyte apoptosis. The expression of mRNA and proteins of liver bile acid transporters such as BSEP,MRP2,NTCP and OATP were down-regulated significantly by GTW to inhibit bile acid excretion and absorption,resulting in cholestatic liver injury. Moreover,GTW was considered to be involved in hepatic oxidative stress injury,although it down-regulated SOD1 and GPX-1 mRNA expression without significant difference in MDA and GSH levels. In vitro,we found that TP was the main toxic component in GTW,which could inhibit cell viability up to 80% in Hep G2 and LO2 cells at the dose of 0. 1 μmol·L-1. Next a LC-MS/MS method was used to detect the concentration of triptolid in plasma from rats,interestingly,we found that the content of TP in GTW was always higher than in the same amount of TP,suggesting the other components in GTW may affect the TP metabolism. Finally,we screened the substrate of p-glycoprotein( p-gp) in Caco-2 cells treated with components except TP extrated from GTW,finding that wilforgine,wilforine and wilfordine was the substrate of p-gp. Thus,we speculated that wilforgine,wilforine and wilfordine may competitively inhibit the excretion of TP to bile through p-gp,leading to the enhanced hepatotoxity caused by GTW than the same amount of TP.


Subject(s)
Animals , Caco-2 Cells , Chemical and Drug Induced Liver Injury , Pathology , Chromatography, Liquid , Diterpenes , Toxicity , Drugs, Chinese Herbal , Toxicity , Epoxy Compounds , Toxicity , Female , Glycosides , Toxicity , Humans , Liver , Phenanthrenes , Toxicity , Plant Extracts , Toxicity , Rats , Rats, Wistar , Tandem Mass Spectrometry , Tripterygium , Toxicity
20.
Article in Chinese | WPRIM | ID: wpr-773541

ABSTRACT

OBJECTIVE@#To evaluate the long-term clinical outcomes of two-stage closed sinus lift for the maxillary sinus with residual bone height (RBH) of 1-3 mm in the posterior maxillary.@*METHODS@#Seventy-eight patients with maxillary posterior tooth loss (1 mm≤RBH≤3 mm and alveolar ridge width ≥5 mm) were treated with two-stage closed sinus lift at the Dental Implantation Center of our hospital between March, 2012 and December, 2014. Coral hydroxyapatite powder and 148 implants were implanted. The superstructure was fixed within 6 months after the operation and the patients were followed up for 1-5 years for assessing the patients' satisfaction, postoperative response, stability and survival rates of the implant, soft tissue condition, bone height of maxillary sinus floor elevation and the marginal bone loss.@*RESULTS@#Perforation of the maxillary sinus floor occurred in 3 (3.85%) of the cases. Twenty-three (30.67%) patients complained of mild pain, and 52 (69.33%) did not experience headache or fever or reported obvious pain or swelling after the operation. The overall response to the operation was favorable. The ISQ value was 58.39±1.39 immediately after the operation, and increased significantly to 81.88±1.22 at 6 months ( < 0.05). During the healing period and the follow-up, none of the implants fell off, and the implant survival rate was 100%. The peri-implant probing depth and modified sulcus bleeding index at 1 year after sinus lifting were similar to those at 5 years after the operation ( > 0.05), but the sinus floor elevation and marginal bone resorption at the two time points differed significantly ( < 0.05).@*CONCLUSIONS@#Compared with lateral wall lifting, two-stage close lifting of the maxillary sinus floor is associated with less trauma and less discomfort, and effectively solves the problem of severe alveolar bone height deficiency in the maxillary posterior region to achieve favorable long-term clinical outcomes.


Subject(s)
Bone Resorption , Dental Implantation, Endosseous , Follow-Up Studies , Humans , Maxilla , Maxillary Sinus , Sinus Floor Augmentation , Treatment Outcome
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