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Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.
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Objective:To investigate the inhibitory effect and killing mechanism of Bcl-2 BH4 selective inhibitor BDA-366 on NK/T cell lymphoma (NK/TCL) .Methods:Human NK cell leukemia cell line YT and human NK/TCL cell line NK92 cells were treated with 0, 0.05, 0.10, 0.20, 0.30, 0.40, 0.50 μmol/L BDA-366. CCK-8 assay was used to calculate the half inhibitory concentration (IC 50) value of BDA-366 on these cells. The apoptosis levels of cells in control group and IC 50 BDA-366 treated group were detected by flow cytometry. Western blotting was used to detect the expression levels of apoptosis-related proteins in cells of control group and 1/2 IC 50, IC 50, 2× IC 50 BDA-366 treated groups. TMRE and Fluo-3 fluorescent probe were used to detect mitochondrial membrane potential of control group and IC 50 BDA-366 treated group, and the intracellular Ca 2+ concentration of control group, IC 50, 2× IC 50 BDA-366 treated groups. NOD-SCID mice in control group and 10 mg/kg BDA-366 intraperitoneal injection group were weighed and HE staining was performed to evaluate the toxicity of BDA-366 in vivo. Results:The IC 50 of BDA-366 for YT and NK92 cells were 0.065 and 0.086 μmol/L respectively. The apoptosis rates of YT cells in the control group and 0.065 μmol/L BDA-366 group were (6.62±1.59) % and (34.60±3.06) % respectively. The apoptosis rates of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were (5.57±0.88) % and (29.18±0.90) % respectively, both with statistically significant differences ( t=14.05, P<0.001; t=32.58, P<0.001). The relative expression of Bax in NK92 cells of the control group, 0.043, 0.086 and 0.172 μmol/L BDA-366 groups were 0.85±0.00, 1.26±0.04, 1.51±0.18, 1.15±0.10 ( F=20.70, P<0.001), the relative expression of Bax in BDA-366 groups were higher than that in the control group (all P<0.05). The fluorescence intensity of TMRE of YT cells in the control group and 0.065 μmol/L BDA-366 group were 8 372.00±330.47 and 6 419.67±311.34, and that of NK92 cells in the control group and 0.086 μmol/L BDA-366 group were 9 169.00±535.72 and 7 311.67±295.52 respectively, and there were statistically significant differences ( t=7.45, P=0.002; t=5.26, P=0.006). In YT cells, the intracellular Ca 2+ concentrations of 0.065 and 0.130 μmol/L BDA-366 groups were significantly higher than that of the control group (5 791.67±220.45, 6 729.33±585.39, 4 874.67±112.61, F=19.16, P=0.003) ( P=0.039; P=0.002). In NK92 cells, the intracellular Ca 2+ concentrations of 0.086 and 0.172 μmol/L BDA-366 groups were significantly higher than that of the control group (4 553.67±17.62, 4 740.33±254.50, 4 185.67±17.67, F=10.96, P=0.010) ( P=0.039; P=0.007). There was no statistically significant difference in body weight change on day 12 compared with day 0 of NOD-SCID mice between BDA-366 group and control group [ (3.18±0.01) g vs. (2.73±0.58) g, t=0.60, P=0.570], and HE staining showed no abnormal morphology of heart, liver, spleen, lung and kidney in BDA-366 group. Conclusion:BDA-366 promotes NK/TCL cells apoptosis in vitro, but does not cause weight loss and morphological changes of organs by HE staining in vivo. The inhibitory effect of BDA-366 on NK/TCL cells may be achieved by increasing Bax expression, inducing Ca 2+ release and reducing mitochondrial membrane potential.
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OBJECT IVE To study the effects of ergosterol peroxide derivatives EP-3P on the proliferation ，migration and invasion of human tripe negative breast cancer cell MDA-MB- 231，and to provide reference for the development of breast cancer related drugs. METHODS MTT assay was adopted to detect the proliferation of MDA-MB- 231 cells after treated with 0（blank control），1.25，2.5，5，10，20，40 μmol/L EP-3P for 24，48 and 72 h. Wound healing assay and Transwell chamber method were adopted to detect the migration and invasion ability of MDA-MB- 231 cells after treated with 0（blank control ），5，10，20 EP-3P for 24 h. The apoptosis and cell cycle distribution were detected by flow cytometry. Western blot assay was used to detect the expressions of B-cell lympho ma-2（Bcl-2），Bcl-2 associated X protein （Bax），caspase-3，cleaved-caspase-3，cytochrome C （Cyt-C），matrix metalloproteinase- 2（MMP-2）and MMP- 9. RESULTS Compared with blank control group ，2.5，5，10，20，40 μmol/L EP-3P could significantly increase the inhibitory rate of cell proliferation （P＜0.05 or P＜0.01）in a dose and time- dependent manner. After 24 h treatment of EP- 3P（10，20 μmol/L），the rate of cell migration and the number of invasive cells were decreased significantly （P＜0.01），and cell was arrested at G 2/M stage （P＜0.05 or P＜0.01）；the apoptotic rate was increased significantly （P＜0.05）；the protein expressions of Bax ，Cyt-C and cleaved-caspase- 3 were upregulated significantly ， while those of Bcl- 2，caspase-3，MMP-2 and MMP- 9 were downregulated significantly （P＜0.01）. CONCLUSIONS EP-3P can inhibit the proliferation ，migration and invasion of human tripe negative breast cancer cells MDA-MB- 231 through mitochondrial mediated endogenous caspase pathway ，and induce the apoptosis of cells .
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The organ-system-centered medical integrated teaching mode has become the trend of modern medical education. This model combines basic medicine with clinical medicine closely. It has been widely conducted domestically and abroad for training qualified clinicians as the main task. This paper summarized the experience of integrated curriculum reform of the digestive system in Chongqing Medical University, analyzed the performance of students involved in curriculum reform, explored the problems in the curriculum reform combined with the actual situation of Chongqing Medical University, and investigated possible solutions to accumulate the experience for further deepening the integrated curriculum reform.
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Objective:To observe the clearance strategies of hemiplegic stroke survivors with foot drop.Methods:Thirty hemiplegic stroke survivors with foot drop formed the observation group and 30 healthy counterparts constituted the control group. A three-dimensional motion capture system was used to observe and compare the minimum toe clearance (MTC) and its variability between the two groups to draw the motion trajectory of the toe in the swing phase of their gaits. The gait parameters were correlated with the toe clearance.Results:The average MTC of the observation group subjects on both the hemiplegic and non-hemiplegic side (12.01±3.36 and 22.38±5.51mm) was significantly smaller than the control group′s averages. The variability of their MTCs on both sides was also significantly greater. Clearance on the hemiplegic side was significantly less and its variability was significantly greater. Among the observation group, MTC on the hemiplegic side was positively correlated with walking speed, step length, swing phase percentage, maximum angle of hip extension, maximum angle of knee flexion, maximum angle of ankle dorsiflexion, and the range of motion of the knee and ankle joints.Conclusions:Hemiplegic stroke survivors with foot drop walk unstably with little toe clearance. It is necessary to intervene at the hip, knee and ankle to improve their obstacle clearance.
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Engineering education is an important part of China's higher education. With the deepening of the connotation of new engineering talents training, it is timely to carry out the curriculum reform in all directions and improve the quality of engineering talents. In order to highlight the characteristics of fostering new engineering talents, specialized courses and practical courses are becoming the focus of curriculum teaching reform. However to this end, it is urgent to explore how to strengthen fostering talents with engineering characteristics in the professional foundation courses. Taking the biochemistry course as an example, problem-based learning teaching methods were employed, appropriate teaching cases were selected, scientific and technical problems based instructional designs were explored, and students were guided to condense, analyze and solve problems. This study aims to transform the learning attitude of students from "passive" to "active", enhance students' thinking skills, highlight the engineering application of science and technology, lay the foundation for continuous and even lifelong learning, and provide a reference for fostering talents under the new engineering background.
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Humans , Problem-Based Learning , Learning , Students , Curriculum , BiochemistryABSTRACT
Objective:To evaluate the value of 18F-FDG uptake features in differential diagnosis of benign and malignant solitary pulmonary lesions. Methods:A total of 274 patients (181 males, 93 females, age: (61.0±10.2) years) with solitary pulmonary lesions who underwent 18F-FDG PET/CT between September 2010 and March 2017 were retrospectively analyzed. The 18F-FDG uptake features of lesions were divided into 5 types: full uptake (Group A), circular uptake (Group B), multi-focus uptake (Group C), mild uptake (Group D) and no-uptake (Group E). According to the pathology or follow-up results, the incidences of benign and malignant lesions in each group were analyzed. The diagnostic efficiencies of 18F-FDG uptake feature classification(A+ B=malignancy, C+ D+ E=benign) and SUV method (lesions with SUV max≥2.5 was taken as the malignancy) were calculated. χ2 test and ROC curve were used to analyze the data. Results:The malignant incidences of Groups A-E were 86.25%(138/160), 71.05%(27/38), 31.25%(10/32), 43.48%(10/23) and 14.29%(3/21), respectively ( χ2=79.49, P<0.001), and the rate of Group A was the highest ( χ2 values: 5.11-55.84, all P<0.05). There were significant differences in the malignancy incidence between A+ B group and C+ D+ E group (83.33%(165/198) vs 30.26%(23/76)), and between SUV max≥2.5 group and SUV max<2.5 group (76.09%(175/230) vs 29.55%(13/44); χ2 values: 71.83 and 37.15, both P<0.001). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the 18F-FDG uptake feature classification and the SUV method were 87.77%(165/188) vs 93.09%(175/188), 61.63%(53/86) vs 36.05%(31/86), 79.56%(218/274) vs 75.18%(206/274), 83.33%(165/198) vs 76.09%(175/230), 69.74%(53/76) vs 70.45%(31/44), respectively. ROC curve analysis showed that the diagnostic accuracy of the 18F-FDG uptake feature classification was higher than that of SUV method (AUCs: 0.747, 0.646; Z=4.05, P<0.001). Conclusions:18F-FDG uptake feature classification can improve the diagnostic specificity and accuracy of solitary pulmonary lesions. The multi-focus uptake feature maybe a sign of benign lesions, which still needs more researches to confirm.
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Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.
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Objective:To explore the relationship between blood test indicators and their changes and impaired fasting blood glucose, and to conduct risk prediction research.Methods:This study selected people who underwent a physical examination at a health management center in Jinan from 2018 to 2019, with an interval of 6 months or more between the two physical examinations, and had no history of diabetes and normal fasting blood sugar during the first year of the physical examination. We took the fasting blood glucose level in the second year as the dependent variable, and took the general examination and blood test indicators in the first year as well as the changes of these indicators as independent variables to construct the model. First, the random forest model was used to screen the independent variables, and then the logistic regression model is fitted to calculate the effect values of the independent variables.Results:A total of 4 416 subjects were enrolled in this study. After a 1-year follow-up, 3.45% (133/3 851) subjects developed prediabetic blood glucose, and 0.42% (16/3 851) developed diabetic blood glucose. The sensitivity of the model using blood test indicators to predict the risk of impaired fasting blood glucose after 1 year was 67.1%, and the specificity was 100.0%. The risk of impaired fasting blood glucose after 1 year was high in the population with older age ( OR value was 1.024, 95% CI 1.014-1.035), higher systolic blood pressure ( OR value was 1.018, 95% CI 1.011-1.025), higher body mass index ( OR value was 1.079, 95% CI 1.036-1.125), higher uric acid ( OR value was 1.003, 95% CI 1.002-1.005), higher glutamyl transpeptidase ( OR value was 1.006, 95% CI 1.003-1.010), lower creatinine ( OR value was 0.971, 95% CI 0.957-0.985), lower AST/ALT ( OR value was 0.614, 95% CI 0.411-0.917)) and lower estimated glomerular filtration rate ( OR value was 0.972, 95% CI 0.958-0.988). The sensitivity of the model using the changes of blood test indicators to predict the risk of impaired fasting blood glucose after 1 year was 65.2%, and the specificity was 99.7%. The risk of impaired fasting blood glucose is high in the population with increased triglycerides ( OR value was 1.152, 95% CI 1.057-1.257), increased alkaline phosphatase ( OR value was 1.021, 95% CI 1.012-1.030), increased albumin ( OR value was 1.087, 95% CI 1.029-1.148), increased aspartate aminotransferase ( OR value was 1.006, 95% CI 1.003-1.009), increased weight ( OR value was 1.049, 95% CI 1.019-1.081) within 1 year. Conclusions:The possibility of impaired fasting blood glucose after 1 year is high in the population with older age, higher systolic blood pressure, higher body mass index, higher uric acid, higher glutamyl transpeptidase, lower creatinine, lower AST/ALT and lower estimated glomerular filtration rate. The possibility of impaired fasting blood glucose is high in the population with increased triglycerides, increased alkaline phosphatase, increased albumin, increased aspartate aminotransferase and increased weight with in 1 year. When the above situation occurs in the physical examination, the blood glucose should be monitored and timely intervention should be taken to prevent the development of diabetes.
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Objective:To investigate the effect of licochalcone A on osteoarthritis in rats and its relationship with p38-MAPK inflammatory signaling pathway.Methods:A total of 160 male Wistar rats were randomly divided into blank non-intervention, blank intervention, arthritis non- intervention and arthritis intervention groups with 40 rats in each group. Rats in the arthritis groups were subjected to unilateral anterior cruciate ligament transection, while rats in the blank groups were only subjected to skin incision and suture. Rats in the intervention groups were treated by intra-articular injection of 1 mL 10 μmol/L licochalcone A for 8 successive weeks. Eight weeks later, the cartilage of rats in each group was stained with safranin, and osteoarthritis soft tissue was scored according to Osteoarthritis Research Society International guideline under the optical microscope. The cartilage was cultured in low glucose cell culture medium supplemented with 5% fetal bovine serum for 48 hours. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan and collagen II in the medium were determined by the chemiluminescence reaction method. The expression levels of p38, phosphorylated p38 (p-p38) and matrix metalloproteinase in cartilage tissue were detected by western blot assay. Results:The progress of osteoarthritis in rats treated with licochalcone A was slow. The Osteoarthritis Research Society International score in the arthritis intervention group was significantly lower than that in the arthritis non-intervention group [(3.8 ± 1.7) points vs. (9.7 ± 1.2) points, P = 0.0064]. The contents of nitric oxide, prostaglandin E 2, sulfated glycosaminoglycan, and collagen II in the arthritis intervention group were (77.84 ± 17.65) μmol/mg and (6.78 ± 1.76) ng/mg, (89.78 ± 9.76) μg/mg, and (1.78 ± 0.76) μg/mg, respectively, which were significantly lower than those in the arthritis non-intervention group [(107.56 ± 18.74) μmol/mg, (10.756 ± 1.87) ng/mg, (125.75 ± 8.87) μg/mg, (3.76 ± 0.88) μg/mg, (NO: P = 0.002; PGE 2: P < 0.001; sGAG: P < 0.001; Collagen II: P < 0.001). Western blot assay results revealed that the relative expression of p38, p-p38, p-p38 to total p38 ratio, matrix metalloproteinase in the arthritis intervention group were (3 454 ± 421), (2 072 ± 175), (0.65 ± 0.14 )and (1 776 ± 765), respectively, which were significantly lower than those in the arthritis non-intervention group (5 322 ± 323), (4 257 ± 184), (0.89 ± 0.11), (3 865 ± 874)( p38: P < 0.001; p-p38: P < 0.001; p-p38/p38: P = 0.002; MMP: P = 0.001). Conclusion:Licochalcone A can delay the progression of osteoarthritis in rats with osteoarthritis through inhibiting inflammatory reaction and cartilage matrix degradation, and p38-MAPK signaling pathway may be involved in the regulation process.
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Objective:To investigate the learning curve of laparoscopic transanal total mesorectal excision (taTME) for rectal cancer operated by one or two surgery teams.Methods:The retrospective cross-sectional study was conducted. Based on the concept of real-world research, the clinical data of 1 458 patients undergoing laparoscopic rectal cancer taTME from 44 medical centers who were registered in the Chinese taTME registry collaborative (CTRC) database from May 2010 to May 2020 were collected. The 1 458 patients were divided into cohorts with one surgery team or two surgery teams according to the operation method. Patients with one surgery team underwent taTME by transabdominal operation and then by transanal operation. Patients with two surgery teams underwent taTME by transabdominal and transanal operation simultaneously with duration of the simutaneous operation time ≥30 minutes. The entire surgical process of patients with two surgery teams is not required to be performed by two surgery teams simutaneously. The clinical data were collected from the medical centers with similar operation amount according to the operation time sequence to analyze the difference between different operation stages and explore the learning curve. The operation time was taken as the parameter to carry out cumulative sum analysis and draw the learning curve of laparoscopic rectal cancer taTME in each medical center. The clinicopathological characteristics of patients from two medical centers with the largest difference in learning curves were analyzed. Observation indicators: (1) screening results of clinical data; (2) clinical data collection of patients with one surgery team; (3) surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages; (4) learning curve of the one surgery team; (5) clinical data collection of patients with two surgery teams; (6) surgical situations of laparoscopic rectal cancer taTME from the two surgery teams; (7) learning curve of the two surgery teams. The cumulative sum was calculated by the CUSUM=∑i=1nXi-U, where Xi represented the operation time of each taTME, U represented the average operation time of all cases, and n represented the operation number. Fitting process was conducted on scatter plot of learning curves. Taking the apex of learning curve as the boundary, the learning curve was divided into two stages. The abscissa corresponding to the apex of learning curve was the number of operations that needed to be performed to cross the learning curve. Measurement data with normal distribution were represented as Mean±SD. Comparison between two groups was conducted using the t test and comparison between multiple groups was conducted using the ANOVA. Measurement data with skewed distribution were represented as M( P25,P75), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was analyzed using the rank sum test. Count data were analyzed using the chi-square test or Fisher exact probability. Results:(1) Screening results of clinical data:the clinical data of 661 patients from 7 medical centers with one surgery team and two surgery teams were collected. (2) Clinical data collection of patients with one surgery team: the clinical data of 312 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected including 42 cases in the number 2 medical center, 97 cases in the number 20 medical center, 82 cases in the number 33 medical center, 35 cases in the number 37 medical center and 56 cases in the number 39 medical center, respectively. (3) Surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages: three medical centers including the number 2, number 37 and number 39 medical center with close operation volume provided the clinical data of cases distributed in five operation stages. Among the five operation stages, the proportion of high-quality operation of total mesorectal excision (TME) was ≥17/18, the incidence of postoperative complications was ≤13.3%(4/30) and the incidence of anastomotic leakage was ≤10.0%(3/30). There was no significant difference in the TME quality, postoperative complications or anastomotic leakage among the five operation stages ( P>0.05). There was no significant difference in the operation time among the five operation stages ( χ2=6.950, P>0.05). (4) Learning curve of the one surgery team: the number of operations corresponding to the turning point of learning curve in number 2 and number 20 medical center was 22 and 39, respectively. The number of operations corresponding to the turning points of learning curve in number 33 and number 37 medical center was 15, 66 and 10, 28, respectively. The number of operations corresponding to the turning point of learning curve in number 39 medical center was 20. The overall curve of number 20 medical center was in line with the trend of learning curve and 39 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 20 and number 33 medical center. Cases with the gender of male or female, age, body mass index, cases classified as stage 1, stage 2, stage 3 or stage 4 of the American Society of Anesthesiologists (ASA) Classification, cases with neoadjuvant therapy, duration of postoperative hospital stay of the number 20 medical center were 77, 20, (60±10)years, 24 kg/m 2(22 kg/m 2, 26 kg/m 2), 1, 88, 8, 0, 8, 8, 11 days (9 days, 13 days), respectively, versus 51, 31, (64±11)years, 23 kg/m 2(21 kg/m 2, 26 kg/m 2), 0, 35, 43, 1, 31, 16 days (13 day, 21 day) of number 33 medical center, showing significant differences in the above indicators between the two medical centers ( χ2 =6.442, t=-2.265, Z=-2.032, -6.870, χ2 =22.120, Z=-8.408, P<0.05). (5) Clinical data collection of the two surgery teams: the clinical data of 259 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected, including 46 cases in the number 2 medical center, 47 cases in the number 8 medical center, 78 cases in the number 18 medical center, 43 cases in the number 33 medical center and 45 cases in the number 44 medical center, respectively. (6) Surgical situations of laparoscopic rectal cancer taTME from the two surgery teams: four medical centers including the number 2, number 8, number 33 and number 44 medical center with close operation volume provided the clinical data of cases distributed in four operation stages. Among the four operation stages, the proportion of high-quality operation of TME was ≥50.0%(13/26), the incidence of postoperative complications was ≤35.0%(14/40) and the incidence of anastomotic leakage was ≤22.5%(9/40). There was no significant difference in the TME quality, postoperative complications or operation time among the four operation stages ( χ2 =3.252, 4.733, 8.848, P>0.05). There was a significant difference in the incidence of anastomotic leakage among the four operation stages ( P<0.05). (7) Learning curve of the two surgery teams: the number of operations corresponding to the turning point of learning curve in number 2 and number 8 medical center was 28 and 16, respectively. The number of operations corresponding to the turning points of learning curve in number 18, number 33 and number 44 medical center was 12 and 58, 10 and 36, 14 and 36, respectively. The overall curve of number 2 medical center was in line with the trend of learning curve and 28 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 2 and number 33 medical center. The age and cases with tumor in stage T0 and (or) Tis, stage T1, stage T2, stage T3 or stage T4 of the T staging of the number 2 and number 33 medical center were (60±12)years, 3, 1, 9, 11, 20 and (65±10)years, 2, 3, 22, 15, 0, respectively, showing significant differences in the above indicators between the two medical centers ( t=-2.280, Z=-4.033, P<0.05). Conclusion:Thirty-nine cases of operations was the minimum number for the one surgery team to cross the learning curve of laparoscopic rectal cancer taTME and 28 cases of operations was the minimum number for the two surgery teams to cross the learning curve of laparoscopic rectal cancer taTME.
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Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.
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Background and Objectives@#Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a critical role in the success of lumbar spinal fusion with autogenous bone graft. This study aims to explore the role and specific mechanism of miR-34c-5p in osteogenic differentiation of BMSCs. @*Methods@#and Results: Rabbit model of lumbar fusion was established by surgery. The osteogenic differentiation dataset of mesenchymal stem cells was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed miRNAs were analyzed using R language (limma package). The expressions of miR-34c-5p, miR-199a-5p, miR-324-5p, miR-361-5p, RUNX2, OCN and Bcl-2 were determined by qRT-PCR and Western blot. ELISA, Alizarin red staining and CCK-8 were used to detect the ALP content, calcium deposition and proliferation of BMSCs. The targeted binding sites between miR-34c-5p and Bcl-2 were predicted by the Target database and verified using dual-luciferase reporter assay. MiR-34c-5p expression was higher in rabbit lumbar fusion model and differentiated BMSCs than normal rabbit or BMSCs. The content of ALP and the deposition of calcium increased with the osteogenic differentiation of BMSCs. Upregulation of miR-34c-5p reduced cell proliferation and promoted ALP content, calcium deposition, RUNX2 and OCN expression compared with the control group. The effects of miR-34c-5p inhibitor were the opposite. In addition, miR-34c-5p negatively correlated with Bcl-2. Upregulation of Bcl-2 reversed the effects of miR-34c-5p on ALP content, calcium deposition, and the expressions of RUNX2 and OCN. @*Conclusions@#miR-34c-5p could promote osteogenic differentiation and suppress proliferation of BMSCs by inhibiting Bcl-2.
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End-stage liver disease (ESLD) is a serious threat to human health, and liver transplantation is the only effective treatment. However, most of the patients died in the process of waiting for transplantation due to the shortage of liver source. With the rapid development of biological tissue enginee-ring technology, researchers have established the strategy of 'decellularized and recellularized technology’, which has deve-loped into the first choice for construction of important organs such as the liver and opened up new ideas for the treatment of ESLD. At present, scientists are working on the optimization of this technology, in order to construction a functional 'new liver’ for transplantation. The authors review the feasibility and challenges of the application of this technology and its optimization stra-tegy in the field of regenerative surgery.
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Objective:To analyze the survival and prognostic factors of adult acute lymphoblastic leukemia (ALL) with different consolidation regimens after complete remission by induction therapy.Methods:A total of 93 adult patients with ALL were enrolled from January 2012 to June 2019 in Peking University Shenzhen Hospital. All the patients achieved complete remission induced by VDLCP regimen, and were divided into the standard group, intensive group and transplantation group according to the consolidation treatment. Thirty-four patients in the standard group received an ALL-like chemotherapy regimen based on VDLCP or Hyper-CVAD consolidation for 4-6 courses. Twenty-nine patients in the intensive group received BFM90/95 consolidation treatment for 2 years. Thirty patients in the transplantation group received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after 2-3 courses of consolidation with the original induction regimen. The median follow-up was 18 (3-96) months, and the main follow-up indicators were overall survival (OS) and disease free survival (DFS). Prognostic factors of adult ALL patients and treatment-related deaths in each group were analyzed.Results:The 3-year OS rates of the standard group, intensive group and transplantation group were 54.0% (95% CI: 35.3%-72.6%), 71.8% (95% CI: 41.0%-94.5%), 62.3% (95% CI: 43.6%-80.9%), with a statistically significant difference ( χ2=6.110, P=0.047). The 3-year DFS rates of the three groups were 31.4% (95% CI: 12.9%-49.8%), 72.1% (95% CI: 52.3%-91.9%), 65.7% (95% CI: 45.3%-86.1%), with a statistically significant difference ( χ2=13.831, P=0.001). There were no significant differences in OS and DFS between the intensive group and the transplantation group ( χ2=0.709, P=0.400; χ2=0.046, P=0.830). OS and DFS of the intensive group were better than those of the standard group ( χ2=5.346, P=0.021; χ2=10.326, P=0.010). Multivariate analysis suggested that bone marrow minimal residual disease (MRD) negative on day 14-21 of chemotherapy was an independent prognostic factor affecting adult ALL ( HR=0.114, 95% CI: 0.015-0.841, P=0.033). The 3-year OS rates of Ph + ALL patients who received and did not receive allo-HSCT were 53.5% (95% CI: 23.1%-83.8%), 52.4% (95% CI: 23.8%-81.0%), the 3-year DFS rates were 77.1% (95% CI: 54.2%-100.0%), 35.0% (95% CI: 4.8%-65.2%), and there were no significant differences between the two groups ( χ2=3.600, P=0.223; χ2=3.824, P=0.050). The treatment-related mortalities of the non-transplantation group (standard group + intensive group) and the transplantation group were 3.2% (2/63) and 20.0% (6/30), and the treatment-related mortality of the non-transplantation group was significantly lower than that of the transplantation group ( χ2=7.318, P=0.007). Conclusion:Adult ALL has a poor prognosis. The 3-year OS rate and 3-year DFS rate of BFM intensive consolidation therapy are better than those of standard consolidation therapy, achieving a similar effect to allo-HSCT, but treatment-related mortality does not increase significantly. Patients with bone marrow MRD negative on the day 14-21 of chemotherapy have the better OS and DFS.
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Immunosuppressants, which are commonly used for liver transplantation, mainly included calcineurin inhibitors, such as ciclosporin (CsA) and tacrolimus (FK506); glucocorticoid drugs, such as prednisone and prednisolone; cytotoxic drugs, such as azathioprine, mycophenolate mofetil and cyclophosphamide; mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus; antibody drugs, such as polyclonal or monoclonal antibodies and interleukin (IL)-2 receptor antibodies, etc. Although many categories of immunosuppressants are available, FK506 is the most commonly adopted in liver transplant recipients. However, FK506 can provoke significant adverse effects in the late stage of liver transplantation, especially severe infection and nephrotoxicity. Consequently, it is an urgent task and research hot spot to develop new immunosuppressants with strong immune tolerance and mild adverse effects in clinical practice. In this article, the research progress on immunosuppressants and the research and development status of new immunosuppressants for liver transplantation were reviewed.
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Objective:To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS).Method:The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS.Results:Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%( P=0.014)and 90.5%( P=0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions:FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.
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Objective:To investigate the value of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in the detection of prostate cancer recurrence at low serum prostate specific antigen (PSA) level. Methods:From July 2018 to June 2019, 45 patients (age: 59-74 years) with suspected biochemical recurrence of prostate cancer with low PSA level (<2.0 μg/L) who underwent 18F-PSMA-1007 PET/CT examinations in Shanxi Tumor Hospital were retrospectively analyzed. Four patients with PSA<0.2 μg/L were not included in the statistical analysis due to the small sample. Among the remaining 41 patients with 0.2 μg/L≤PSA<2.0 μg/L, 10 were with 0.2 μg/L≤PSA<0.5 μg/L, 14 were with 0.5 μg/L≤PSA<1.0 μg/L, 17 were with 1.0 μg/L≤PSA<2.0 μg/L. PET/CT imaging were performed within 2 weeks after the examination of serum PSA. All patients were divided into low-moderate-risk group ( n=12) and high-risk group ( n=29) according to the National Comprehensive Cancer Network (NCCN) guidelines. χ2 test, Fisher′s exact test and Spearman rank correlation were used to analyze the data. Results:Patients were followed up for 7 (4-15) months, and all 45 patients were confirmed by pathology or follow-up. There were 31 patients with recurrence and 14 patients without recurrence. The sensitivity, specificity and accuracy were 100%(31/31), 13/14, 97.78%(44/45)respectively. One patient with PSA<0.2 μg/L presented retroperitoneal lymph node metastasis. Among 41 patients with 0.2 μg/L≤PSA<2.0 μg/L, 31(75.61%) were with at least one recurrent lesion by 18F-PSMA-1007 PET/CT. There were 20 cases of local recurrence, 13 cases of lymph node metastasis, 14 cases of bone metastasis. The detection efficacies of 18F-PSMA-1007 PET/CT were 5/10 for patients with 0.2 μg/L≤PSA<0.5 μg/L, 11/14 for those with 0.5 μg/L≤PSA<1.0 μg/L, and 15/17 for those with 1.0 μg/L≤PSA<2.0 μg/L ( χ2=4.641, P>0.05). The positive results of 18F-PSMA-1007 PET/CT were positively correlated with serum PSA value and risk group ( r values: 0.394, 0.384, both P<0.05). Conclusion:18F-PSMA-1007 PET/CT is a valuable tool for detecting biochemical recurrence of prostate cancer with low PSA level.
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MarR family transcription regulators are ubiquitous among bacteria and archaea. They extensively control multiple cellular processes and elaborately regulate the expression of genes involved in virulence, stress response and antibiotics at translational level. In Xanthomonas campestris pv. campestris, insertional inactivation of MarR family transcription regulator HpaR (XC2827) resulted in significantly decrease in virulence and increase in the production of the extracellular proteases. Here, we reported that the genome of Xcc 8004 encodes nine MarR family transcription regulators. The MarR family transcription regulators, HpaR (XC2827) and XC0449, were heterologous expressed and purified. In vitro MST and Pull-down assay confirmed the physical interaction between HpaR and XC0449. Phenotypical assay determined that deletion of XC0449 resulted in substantial virulence attenuation. In vitro EMSA, in vivo qRT-PCR and GUS activity assay identified that HpaR and XC0449 coordinately act as the transcriptional activator to regulate the expression of the virulence-associated gene XC0705, and eventually control the bacterial virulence and the production of extracellular proteases.
Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Transcription Factors , Virulence , Xanthomonas campestrisABSTRACT
Objective@#To investigate the genetic characteristics of VP1 genes carried by coxsackievirus A16 strains isolated from cases of hand foot and mouth disease (HFMD) in Shenzhen during 2016 to 2017.@*Methods@#Fecal and anal swab specimens were collected from patients with mild HFMD in four sentinel hospitals and the Institute of Pathogen Biology, Shenzhen Center for Disease Control and Prevention, China during 2016 to 2017. All specimens were tested for CVA16 viral RNA using real-time RT-PCR. The VP1 genes of 51 randomly selected CVA16 strains were amplified by RT-PCR and then sequenced using TaKaRa Biomedical Technology (Dalian). Bioinformatics software, including Mega6.02, BioEdit and DNAStar, was used for comparison and analysis of the VP1 genes.@*Results@#CVA16 strains in Shenzhen during 2016 to 2017 mainly belonged to B1a and B1b subtypes as well as an emerging subtype B3. The epidemic of B1b subtype was found in both 2016 (28 strains) and 2017 (19 strains), while the B1a subtype (two strains) was only detected in 2017. Two B3 subtype strains were detected in 2017. The strains of B1b subtype were closely related to the strains isolated in Shanghai (JQ314149), Wenzhou (KP289416) and Beijing (KU254598), while the B1a subtype strains were closely related to the strains isolated in Kunming (JQ316639) and Tailand (GQ184139). The B3 subtype strain was an emerging CVA16 epidemic strain in mainland China. Further comparison of the CVA16 epidemic strains in Shenzhen area during 2016 to 2017 with the CVA16 strains causing severe neurological symptoms showed that two amino acid mutations (S14N and M23L) were found in VP1 protein.@*Conclusions@#The epidemic strains of CVA16 were B1b subtype in Shenzhen area in 2016. However, B1a, B1b and the emerging B3 subtype strains were prevalent in 2017. Compared with the CVA16 strains causing severe neurological symptoms, the CVA16 strains circulating in Shenzhen during 2016 to 2017 carried two amino acid mutations inVP1 protein.