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1.
Acta Pharmaceutica Sinica ; (12): 1921-1926, 2021.
Article in Chinese | WPRIM | ID: wpr-887006

ABSTRACT

In this study, a rat morphine drug discrimination model with a fixed ratio (FR) of 10 (FR10) was established using different methods to explore which methods can shorten the modeling time and test the dose-response relationship and median effective dose (ED50) value. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of Shanghai InnoStar Bio-tech Co., Ltd. Forty rats were initially shaped to press lever under a fixed-ratio schedule of food reinforcement. The animals that were successfully trained under a FR10 schedule of food reinforcement were divided into two groups, namely the single-lever + double-lever training group 1 and the double-lever training group 2. In each group, rats were trained to discriminate morphine at 5.6 mg·kg-1 from saline by the intraperitoneal route. After training, different doses of morphine were used to substitute for training dose of morphine, the dose-response curve for morphine were identified in rats, and the ED50 value was calculated. The results showed that, in food training phase: 34 rats successfully entered the discrimination training during food training; in discrimination training phase: 14 animals in group 1 met the discrimination training standard for the first time, which took about (40.71 ± 2.93) days, and there were 13 animals in group 2 that met the discrimination training criteria for the first time, and it took about (51.15 ± 2.55) days. It can be seen that the method of single-lever + double-lever training is better than single-lever training, and the difference is significant compared with group 1 (P ˂ 0.05); in generalization test phase: there are 17 rats completed morphine generalization test, and the percentages of morphine-lever responses produced by the generalization test of different doses of morphine (0, 0.1, 0.5, 1, 3, 5.6, and 10 mg·kg-1) were (9.56 ± 3.13) %, (9.01 ± 5.83) %, (13.82 ± 7.95) %, (29.04 ± 10.13) %, (41.70 ± 10.65) %, (85.36 ± 7.16) %, (94.56 ± 2.76) %, respectively. The results showed that the discriminative stimulative effect induced by morphine dose between 0-10 mg·kg-1 increased in a dose-dependent manner, producing a good dose-response curve, and the ED50 value of morphine was 4.74 mg·kg-1 by linear fitting. The above results showed that, the FR10 morphine drug discrimination model has been successfully established using different methods; the single-lever + double-lever training method is better than the single-lever training, and can relatively shorten the discrimination training cycle.

2.
Acta Pharmaceutica Sinica ; (12): 2403-2409, 2021.
Article in Chinese | WPRIM | ID: wpr-886957

ABSTRACT

Studies have shown that women's menopause caused by permanent cessation of ovarian function is closely related to lipid metabolism disorders. Er-xian Decoction has been used in the clinical treatment for gynecological diseases and has a good effect on diseases related to reduced sex hormone function. In this study, metabolomics was performed on bilateral ovariectomized model rats within 12 weeks after modeling to mimic the physiological state of menopausal women in different menopausal stages and Er-xian Decoction dosed model rats. The results of liver oil red O staining sections showed lipid metabolic disorder of bilateral ovariectomized model rats and the regulating effects of Er-xian Decoction. 46 potential biomarkers (6 steroid hormones, 3 sphingolipids, 11 phospholipids and 26 glycerides) in plasma and 32 potential biomarkers (1 steroid hormones, 20 phospholipids and 11 glycerides) in liver were obtained based on lipidomics analysis. Then, we analyzed the differential metabolic pathways and construct the lipid metabolism network significantly regulated by Er-xian Decoction. The results provided valuable information for in-depth understanding of the gradual changes on lipid metabolism disorders under menopausal conditions and the characteristics and mechanisms of compound Er-xian Decoction's regulatory effects. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00000918).

3.
Article in Chinese | WPRIM | ID: wpr-884670

ABSTRACT

Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.

4.
Article in Chinese | WPRIM | ID: wpr-884484

ABSTRACT

Objective:To analyze the levels of individual doses to radiation workers receiving medical radiation exposure in hospitals in Jiangxi province, so as to provide reference for radiation protection.Methods:The radiation workers of different types in medical institutions in Jiangxi were investigated from 2014 to 2018, involving diagnostic radiology, radiotherapy, nuclear medicine and interventional radiology. Statistical analyses were made of the individual doses to medical radiation workers in the province.Results:The total number of monitored workers were 23 833 with average annual individual effective dose of 0.316 mSv. NR1 and NR5, the ratios of the number of workers receiving annual individual doses exceeding 1 and 5 mSv to the total monitored workers were 4.32% and 0.10%, respectively. During the five-year period, the average annual individual effective dose showed a upward and then downward trend, with peak appearing in 2017. A total of 17 909 diagnostic radiologists were monitored, accounting for 75.14% of the total number of monitored workers. The average annual individual effective dose received by workers was 0.329 mSv, the highest, in interventional radiology, followed by diagnostic radiology 0.318 mSv, nuclear medicine 0.283 mSv, and radiotherapy 0.269 mSv, respectively. There were statistically significant differences among radiation workers of different types ( χ2=489.39, P<0.001). Conclusions:The average annual individual effective dose to the radiation workers in medical institutions in Jiangxi province meets the relevant national standards, but with an upward trend in nuclear medicine. The higher levels of individual doses to radiation workers are seen in primary and secondary hospitals. It should be strengthen the oversight of radiation workers in nuclear medicine and in primary and secondary hospitals.

5.
Article in Chinese | WPRIM | ID: wpr-884469

ABSTRACT

Objective:To analyze the efficacy and safety of radioactive 125I seed implantation in the treatment of unresectable early-stage non-small cell lung cancer (NSCLC), in order to provide data for clinical practice and relevant research. Methods:A retrospective study was conducted on the data of 39 patients with early-stage NSCLC who received CT-guided radioactive 125I seed implantation from Dec 2010 to Dec 2018 in multiple hospitals.The seed implantation process consisted of preoperative planning and design, CT-guided puncture, seed implantation, and postoperative evaluation and dose verification.The efficacy and complications of the treatment were analyzed.The clinical efficacy was evaluated by adopting the Response Evaluation Criteria in Solid Tumors (RECIST) (v1.1) and the adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results:All the patients were 70 years old on average (51-85). The median lesion diameter was 2.7 cm (1.1-6.0 cm), the median seed activity was 0.7 mCi (0.6-0.8 mCi), while the median follow-up duration was 29 months (3-97 months). Meanwhile, the 1-, 3-, and 5-year overall local control rates were 89.5%, 79%, and 79%, respectively, and the 1-, 3-, and 5-year overall survival rates were 100%, 74.8%, and 49.9%, respectively.Local recurrence and distant metastasis were the main causes of failure, accounting for 17.9% (7 cases) each.The incidence of pneumothorax was 56.4% (22 cases), among which nine cases (23.1%) required invasive closed thoracic drainage.Only 1 case of grade-2 radiation pneumonia (2.6%) was observed, with no other adverse reactions such as dermatoses, esophagitis, or myelitis being discovered.As indicated by univariate analysis, the patients with KPS scores of 80-90, pathological type of adenocarcinoma, T stage of T 1-2, and D90>180 Gy exhibited better local control ( χ2=6.202, P<0.05). Meanwhile, high D90 was also associated with a higher survival rate ( χ2=6.907, P<0.05). Conclusions:Radioactive 125I seed implantation is a safe and effective treatment for unresectable early-stage NSCLC.In cases where external beam radiotherapy is not available, radioactive 125I seed implantation can be considered as one of the treatment options.Pneumothorax is the most common complication of radioactive 125I seed implantation, and adenocarcinoma (pathological type) and higher values of D90 are predictors of better local control.

6.
Article in Chinese | WPRIM | ID: wpr-882588

ABSTRACT

Turkey is a presidential republic country located in the Eurasian continent, which has a universal health coverage since the health reform in 2003. The leading causes of death in this country are ischemic heart disease, stroke, and lung cancer. Besides, lower respiratory infections, chronic kidney disease, and hypertensive heart disease are the diseases which have a fastest growing rate. Chinese acupuncture was officially recognized by Turkey in 1991 with the promulgation of Acupuncture Treatment Legislation. At present, only trained practitioners and dentist could conduct acupuncture treatment, which was stated in Regulation of Tradition and Complementary Medicine Practice. The application of Turkish acupuncture and moxibustion is still applied in a simplified way that lack of TCM theory. Moreover, Chinese herbal medicine is still not officially recognized and still under control of the Ministry of Agriculture. Therefore, it is suggested to introduce TCM theory in the spread of acupuncture, to promote acupuncture research and clinical practice, to clarify the different standards between the two countries, and to cooperate in Chinese medicine researches, especially those related to the local high incidence and refractory disease so as to promote the development of TCM in Turkey and provide medical services for local residents.

7.
Acta Pharmaceutica Sinica ; (12): 1580-1590, 2021.
Article in Chinese | WPRIM | ID: wpr-881556

ABSTRACT

The tumor microenvironment (TME), a dynamic and complex local environment, interacts with the tumor cells and is closely related to tumor growth, metastasis, immune escape and drug resistance. Thus, targeting the TME has been a worldwide focus in cancer therapy. Many natural products possess the advantages of multiple targets, multiple pathways and wide pharmacological functions, and are the main source of antitumor drugs. In recent years studies have found that some natural products had advantageous effects on the TME. In this review, we summarize the components and functions of the TME and some natural products that target the TME, with references to the drug therapy of cancer.

8.
Article in Chinese | WPRIM | ID: wpr-880114

ABSTRACT

OBJECTIVE@#To investigate the damaging of human umbilical vein endothelial cells (HUVEC) induced by antiplatelet integrin β3 antibodies in vitro.@*METHODS@#The serum from 36 chronic ITP patients were collected, flow cytometry and monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to collect antiplatelet integrin β3 antibodies from the serum of the patients. After HUVEC were treated by ITP patient serum (PS) containing anti-integrin β3 antibodies, the cell damage was detected by Lactate dehydrogenase (LDH) assay, cell apoptosis was detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by Reverse transcription-Quantitative real-time PCR (RT-qPCR), and expression of Apoptosis-related signaling pathway protein Akt and related protein Bax were detected by Western blot. HUVEC were treated by PS combined with Akt activator SC79, the cells damage were detected by LDH assay, apoptosis of the cells were detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by RT-qPCR.@*RESULTS@#Among 36 cases of serum from the chronic ITP patients, 5 patients' serum containing anti-integrin β3 antibodies were collected. After HUVEC was treated by PS, the viability of LDH was significant increased(P<0.05), so as for the apoptosis of the cells(P<0.05), the expression of gene and protein of Bax was increased up-regulated(P<0.05), the protein expression of pAkt was down-regulated(P<0.05). Comparing with HUVEC cultured with PS alone, the viability of LDH of HUVEC treated by PS combined with SC79 was significantly reduced(P<0.05), so as for the apoptosis of the cells(P<0.05), and gene expression of Bax was significantly decreased(P<0.05).@*CONCLUSION@#Anti-integrin β3 serum can cause the damage and apoptosis of HUVEC through Akt signaling pathway,the apoptotic effects of anti-integrin β3 antibodies to HUVEC was effectively reversed by SC79.


Subject(s)
Apoptosis , Cells, Cultured , Human Umbilical Vein Endothelial Cells , Humans , Integrin beta3 , Signal Transduction
9.
Article in Chinese | WPRIM | ID: wpr-880029

ABSTRACT

OBJECTIVE@#To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH@*METHODS@#Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed.@*RESULTS@#All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34@*CONCLUSION@#The percentage of CD34


Subject(s)
ADP-ribosyl Cyclase 1 , Antigens, CD34 , Flow Cytometry , Humans , Leukemia, Myeloid, Acute , Neoplastic Stem Cells , Prognosis , Recurrence , Remission Induction
10.
Article in Chinese | WPRIM | ID: wpr-879072

ABSTRACT

The physical properties of powder and granules are the critical quality attributes for the process control of Suhuang Zhike Capsules, a big brand traditional Chinese medicine. This paper took the production of 25 batches of real-world Suhuang Zhike Capsules dry extract powder and granules intermediates as the research object. Firstly, a method for testing the physical properties of Suhuang Zhike Capsules powder and granules with 19 physical indicators was established. The results showed that the granules of dry extract powder after granulation had a smaller particle size, wider particle size distribution range and poor fluidity, which easily caused the problem of over-limit capsule loading. Secondly, correlation analysis, principal component analysis and cluster analysis were used for mathematical statistics. The correlation analysis showed that the density of dry extract powder could affect the chroma and fluidity. At the same time, the particle size in the granules had a stronger effect on the chroma and fluidity than the density. The study also found that the particle size and hygroscopicity of dry extract powder were potentially key physical properties that affected the physical properties of granules. Furthermore, the results of principal component analysis and cluster analysis showed that the consistency of the physical properties between the dry extract powder and intermediate granules was relatively poor. To this end, similarity analysis was carried out, and the quality control method of powder and granules based on physical fingerprint was established. The results showed that the physical fingerprint similarity of 25 batches of dry extract powder was 0.639-0.976, and the physical fingerprint similarity of the gra-nules was 0.716-0.983. With the similarity of 0.85 as the threshold, the batches with abnormal physical properties could be identified. In this study, the process quality control method of Suhuang Zhike Capsules based on the physical properties of powder and granules was established finally, which realized the identification of abnormal batches, and provided a reference for the process quality control of Suhuang Zhike Capsules.


Subject(s)
Capsules , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Powders , Quality Control
11.
Article in Chinese | WPRIM | ID: wpr-879069

ABSTRACT

Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.


Subject(s)
Calibration , Ginkgo biloba , Least-Squares Analysis , Medicine, Chinese Traditional , Plant Leaves , Quality Control , Spectroscopy, Near-Infrared , Tablets
12.
Article in Chinese | WPRIM | ID: wpr-911961

ABSTRACT

Objective:To evaluate the clinical effect of applying the programmed management procedure in the prenatal diagnosis of pyriform sinus fistula(PSF).Methods:This study retrospectively enrolled eight fetuses with PSF who were managed according to the programmed management procedure for prenatal diagnosis of PSF, which was established in January 2016, in Guangzhou Women's and Children's Medical Center from January 2016 to October 2020. The procedure consisted of the detection of fetal neck cysts by prenatal ultrasound followed by further confirmation by MRI, evaluation of the degree of airway compression, indwelling gastric tube after birth, no oral feeding, complement of CT/MRI, and surgical treatment within a limited time after necessary preoperative examination. The prenatal diagnosis, postnatal treatment, and follow-up were summarized using descriptive analysis.Results:(1) Prenatal: The gestational age at the first detection of cervical cysts by prenatal ultrasound was (27.1±4.1) weeks and all the cysts were located on the left side. Prenatal MRI indicated that the largest cysts was (32.0±12.2) mm in diameter, and the tracheal transit index was (10.9±2.8) mm. (2) After birth: Among the eight children, five were males and three were females, with the gestational age of (38.0±0.9) weeks and birth weight of (3 020±459) g. One case was intubated during labor due to a intrauterine tracheal transposition index of 17.4 mm. All infants were not allowed for oral feeding. The median age at CT/MRI examination was 2.5 d (1-8 d), which revealed that the maximum diameter of the cysts was (40.6±6.9) mm and visible air bubbles in all cysts. The infection index before operation was not high and the age at operation was (8.6±2.3) d. All cysts were completely removed and the PSFs were ligated at a higher position, with the average operative duration of (95.0±19.6) min, and the postoperative duration of mechanical ventilation and hospitalization of 5 h (3-71 h) and (8.8±1.0) d, respectively. No complications such as hoarseness were reported. During the follow-up of 4 to 58 months through outpatient clinic and telephone, no recurrence were observed.Conclusions:The programmed management procedure can provide guidance for postnatal treatment of patients with a prenatal diagnosis of PSF, and help to achieve a successful treatment result.

13.
Chinese Journal of Orthopaedics ; (12): 929-937, 2021.
Article in Chinese | WPRIM | ID: wpr-910675

ABSTRACT

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.

14.
Article in English | WPRIM | ID: wpr-897465

ABSTRACT

Purpose@#We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method. @*Materials and Methods@#RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis. @*Results@#We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels. @*Conclusion@#We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.

15.
Article in English | WPRIM | ID: wpr-889761

ABSTRACT

Purpose@#We aimed to develop a novel method for orthotopic colon cancer model, using tissue adhesive in place of conventional surgical method. @*Materials and Methods@#RFP HCT 116 cell line were used to establish the colon cancer model. Fresh tumor tissue harvested from a subcutaneous injection was grafted into twenty nude mice, divided into group A (suture method) and group B (tissue adhesive method). For the group A, we fixed the tissue on the serosa layer of proximal colon by 8-0 surgical suture. For the group B, tissue adhesive (10 μL) was used to fix the tumor. The mortality, tumor implantation success, tumor metastasis, primary tumor size, and operation time were compared between the two groups. Dissected tumor tissue was analyzed for the histology and immunohistochemistry. Also, we performed tumor marker analysis. @*Results@#We observed 30% increase in graft success and 20% decrease in mortality, by using tissue adhesive method, respectively. The median colon tumor size was significantly increased by 4 mm and operation time was shortened by 6.5 minutes. The H&E showed similar tumor structure between the two groups. The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups. Real-time quantitative reverse transcription analysis showed eight out of nine tumor markers are unchanged in the tissue adhesive group. Western blot indicated the tissue adhesive group expressed less p-JNK (apototic marker) and more p-MEK/p-p38 (proliferation marker) levels. @*Conclusion@#We concluded the tissue adhesive method is a quick and safe way to generate orthotopic, colon cancer model.

16.
Protein & Cell ; (12): 769-787, 2021.
Article in English | WPRIM | ID: wpr-888728

ABSTRACT

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

17.
Journal of Experimental Hematology ; (6): 1394-1402, 2021.
Article in Chinese | WPRIM | ID: wpr-922271

ABSTRACT

OBJECTIVE@#To investigate the effect of glycolytic enzyme pyruvate kinase type 2 (PKM2) on the proliferation and apoptosis of human leukemia HL-60 cells.@*METHODS@#si-PKM2 plasmid was transfected into HL-60 cells (set as si-PKM2 group), and blank vector transfected cells were set as control group (si-Ctl group). The expression levels of PKM2 mRNA and protein in si-Ctl group and si-PKM2 group were detected by RT-qPCR and Western blot. CCK-8 cell detection kit was used to detect the proliferation ability of the cells in the two groups. Flow cytometry was used to detect the changes of cell cycle and apoptosis. Western blot and RT-qPCR were used to detect the changes of p-Akt and p-mTOR protein levels in PI3K/Akt/mTOR signaling pathway and the changes of glycolysis-related mRNA levels of the cells in the two groups. The changes in glucose consumption and lactic acid production of the cells were assayed. Over expressed PKM2, HL-60 cells were treated with PI3K inhibitor LY294002 or galactose, the changes in cell proliferation ability, cell cycle and apoptosis, as well as changes in glucose consumption and lactic acid production were detected.@*RESULTS@#Interfered by si-PKM2, mRNA and protein levels of PKM2 in si-PKM2 group significantly decreased, and proliferation ability of the cells was also reduced (P<0.05). After PKM2 knockdown, the cells were significantly blocked at G@*CONCLUSION@#PKM2 knockdown can inhibit the proliferation and induce apoptosis of HL-60 cells, and its molecular mechanism may be related to the PKM2-mediated PI3K/Akt/mTOR-glycolysis, which suggesting that PKM2 may serve as a molecular target for the prevention and treatment of leukemia.


Subject(s)
Apoptosis , Cell Proliferation , Glycolysis , Humans , Phosphatidylinositol 3-Kinases/metabolism , Pyruvate Kinase
18.
J Cancer Res Ther ; 2020 Sep; 16(5): 1165-1170
Article | IMSEAR | ID: sea-213773

ABSTRACT

Context: Owing to the increasing age of the population, the incidence of hepatocellular carcinoma (HCC) in the elderly is increasing annually. Aims: This study aims to investigate the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with low-dose apatinib for unresectable HCC treatment in elderly patients (≥65 years). Settings and Design: The clinical data from 61 elderly patients with unresectable HCC who were retrospectively analyzed. Subjects and Methods: Of these 61 patients, 27 received TACE combined with low-dose (250 mg/qd) apatinib (experimental group), and 34 patients received the standard TACE treatment (control group). The short-term efficacy was evaluated according to the mRECIST1.1 standards, and the mid- and long-term efficacy and safety in the two groups of patients were evaluated. Statistical Analysis Used: Statistical analyses were performed using the Statistical Package for the Social Sciences software (version 20.0; SPSS). Results: Both the objective response rate and disease control rate of the experimental group were significantly higher than those of control group (P < 0.05). The 6-month and 12-month survival rates of the experimental group were significantly higher than those of control group too (P < 0.05). The median survival in the experimental group was longer than in the control group (26.0 months vs. 20.0 months). The adverse reactions related to the intake of apatinib were higher in the experimental than the control group, but were generally alleviated after symptomatic treatment. Conclusions: TACE combined with low-dose apatinib provides an alternative treatment option for elderly patients with unresectable HCC. Our clinical study has proven its safety and efficacy.

19.
Chinese Journal of Radiology ; (12): 474-478, 2020.
Article in Chinese | WPRIM | ID: wpr-868305

ABSTRACT

Objective:To evaluate the feasibility of CT radiomics method in predicting outcomes of simultaneous pulmonary nodules in breast cancer patients after treatment.Methods:Patients with breast cancer confirmed by pathology and with simultaneous pulmonary nodules (diameter>5 mm, number≤5) detected by preoperative CT were retrospectively enrolled in this study. Eighty female patients were included (median age: 52, quartile range: 45, 61). The pulmonary nodules (median size: 6.0 mm, quartile range: 5.5, 7.2 mm) were classified into stable group (without change over 2 years) and change group according to follow-up CT findings. The change group was further divided into improved group and progressive group. Eventually, 54 cases were in the stable group, 26 cases were in the change group. One hundred and five texture features were extracted using the python-based pyradiomics package based on preoperative CT images. Stepwise regression was used to exclude features without significant difference in predicting changes of pulmonary nodules. Classifiers model and 5 fold cross validation method were used to obtain the highest performance in predicting outcomes of pulmonary nodules. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the model.Results:After features exclusion and selection, three radiomics features were used to establish classifiers between stable group and change group. It was showed that the linear discriminate analysis was the optimal model with the specificity, sensitivity, accuracy and area under the ROC curve (AUC) as 0.980, 0.460, 0.813 and 0.770 respectively. One radiomics feature was chosen to establish classifiers between improved group and progressive group. The coarse gaussian support vector machine (CGSVM) was the optimal model, with the specificity, sensitivity, accuracy and AUC as 0.540, 0.920, 0.713 and 0.880 respectively.Conclusions:CT radiomics analysis has the potential to predict the outcomes of simultaneous indeterminate pulmonary nodules in breast cancer patients after treatment, and it may contribute to preoperative treatment and postoperative follow-up planning.

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Article in Chinese | WPRIM | ID: wpr-867952

ABSTRACT

Objective:To explore the role of virtual reduction and design of 3D printed guide template in assisting reduction and internal fixation of comminuted patellar fractures.Methods:A retrospective study was conducted of 12 patients who had been treated for closed patellar fractures from March 2016 to April 2019 at Department of Orthopaedics, Jiangxi Provincial People's Hospital. They were 8 males and 4 females with an average age of 35.4 years (from 22 to 51). All their fractures were type 34-C3 (more than 3 fragments) according to the AO/OTA classification. Their preoperative CT data were imported into software Mimics to print a full patella, upper and lower halves of the patella, and a guide template for reduction. During operation, bone fragments were first temporarily fixated with a fine Kirschner wire after combined together with the assistance of reduction templates for upper and lower hemi-patellas. Next, the whole patella was precisely reset and definitely fixated using patellar ring ligation and tension band wire with the assistance of the reduction guide template for full patellar. Recorded were operation time, fluoroscopic frequency, and visual analogue scale (VAS), knee range of motion (ROM) and knee function B?stman scores at the last follow-up.Results:In this group of patients, operation time averaged 90 minutes (from 75 to 120 minutes), fluoroscopic frequency 4.5 times (from 3 to 8 times), follow-up duration 19 weeks (from 16 to 22 weeks), and fracture healing time 14 weeks (from 11 to 17 weeks). At their last follow-up, X-ray showed good patellar morphology, fine internal fixation positions and an average VAS pain scores of 0.3 (from 0 to 1), their knee joints could be fully straightened, their knee ROM averaged 130°(from 100° to 138°), and their knee B?stman scores 28.8 points (from 21 to 30 points), giving 9 excellent and 3 good cases.Conclusion:3D printed reduction guide templates can significantly improve the efficiency and quality of surgical reduction in comminuted patella fractures, enhancing fixation strength and facilitating early and full range exercise of the knee joint to achieve excellent recovery.

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