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1.
Acta Pharmaceutica Sinica ; (12): 707-715, 2022.
Article in Chinese | WPRIM | ID: wpr-922888

ABSTRACT

We analyzed the anticancer effect and mechanism of the novel indoleamine 2,‍3-dioxygenase 1 (IDO1) inhibitor NLG-919 combined with temozolomide (TMZ) on human glioma cell lines. The anti-tumor activity of NLG-919 and temozolomide after single and combined treatments was detected by MTT assay. Colony formation assay, invasion assay and migration assays were used to detect the effects of NLG-919 and temozolomide alone or in combination on proliferation, invasion and migration of human glioma cells. A flow cytometry assay was used to detect cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential damage (JC-1). An immunofluorescence assay was used to detect the expression level of IDO1 and HPLC was used to detect the expression level of L-kynurenine (Kyn) to explore the anti-tumor mechanism of NLG-919 and temozolomide. The results show that NLG-919 had a weak in vitro inhibitory effect compared to that of temozolomide. The IC50 of NLG-919 on U251 cells and U87 after 72 h was 26.9 and 30.7 μmol·L-1, respectively. However, when NLG-919 was used in combination with temozolomide, its anti-glioma activity was significantly increased. Compared with the single treatment, the combination treatment had a potent ability to inhibit proliferation, invasion and migration of glioma cells. Combination treatment improved the capacity of temozolomide to induce cell cycle arrest and inhibit the growth of glioma cells. NLG-919 significantly down-regulated the expression and activity of IDO1 in glioma cells, and the inhibitory effect was improved after combination with temozolomide, and effectively blocked the production of Kyn through the metabolism of L-tryptophan (Trp). In conclusion, the IDO1 inhibitor NLG-919 and temozolomide showed synergistic effects in the anticancer therapy of human glioma cell lines.

2.
Chinese Journal of Digestion ; (12): 534-540, 2021.
Article in Chinese | WPRIM | ID: wpr-912208

ABSTRACT

Objective:To investigate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophils, lymphocytes and platelets counts in predicting the prognosis of patients with gastric cancer after radical resection.Methods:From January 1, 2012 to January 1, 2015, the data of 2 273 patients with gastric cancer who underwent radical surgery at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. SII value was calculated according to the formula (SII=neutrophil cell count (×10 9/L)×platelet cell count (×10 9/L)/lymphocyte count (×10 9/L)). According to receiver operating characteristic curve (ROC), the optimal cut-off value of SII was determined and the patients were divided into high SII group and low SII group. Chi-square test was used to compare the clinicopathological characteristics and prognosis of the two groups. Kaplan-Meier method was applied to draw survival curve, log-rank test was used for univariate survival analysis, and Cox regression model was used for multivariate survival analysis. The ROC of preoperative SII, pathological TNM stage and their combination for predicting prognosis and recurrence were drawn, and the area under the curve (AUC) values were calculated to compare the predictive power of the three. Results:According to the ROC, the optimal cut-off value of SII was 589.5, and there were 1 180 cases (51.91%) in the high SII (SII≥589.5) group and 1 093 cases (48.09%) in the low SII (SII<589.5) group. Compared with those of the low SII group, the maximum diameter of gastric cancer in the high SII group was mostly ≥5 cm (49.04%, 536/1 093 vs. 56.27%, 664/1 180), the histological types were mostly poorly differentiated to undifferentiated (55.63%, 608/1 093 vs. 61.19%, 722/1 180), the depth of tumor invasion was mainly from T4a to T4b (45.11%, 493/1 093 vs. 54.837%, 647/1 180), and the rate of lymph node metastasis, pathological TNM stage, rate of vascular infiltration, incidence of nerve invasion, Ki-67 expression level, serum carcinoembryonic antigen level and carbohydrate antigen 19-9 level in the high SII group were all higher than those in the low SII group (67.70%, 740/1 093 vs. 80.68%, 952/1 180; 57.64%, 630/1 093 vs. 71.10%, 839/1 180; 55.54%, 607/1 093 vs. 67.03%, 791/1 180; 53.89%, 589/1 093 vs. 64.32%, 759/1 180; 45.29%, 495/1 093 vs. 56.69%, 669/1 180; 56.91%, 622/1 093 vs. 63.20%, 734/1 180; 53.25%, 582/1 093 vs. 57.97%, 684/1 180), and the differences were statistically significant ( χ2=8.842, 11.097, 7.225, 21.467, 50.200, 44.984, 31.687, 25.594, 29.549, 6.612 and 5.119, all P<0.05). The 5-year overall survival rate and disease-free survival rate of the low SII group were 75.66% and 67.61%, respectively, which were both higher than those of the high SII group, (24.92% and 23.31%, respectivily), the differences were statistically significant ( χ2=620.700 and 413.00, both P<0.01). The results of multivariate Cox regression analysis showed that tumor histological type, depth of invasion, pathological TNM stage, vascular invasion and preoperative SII were independent risk factors for postoperative prognosis and recurrence of patients with gastric cancer (odds ratios were 4.126, 2.255, 5.123, 3.826, 6.126, 4.683, 2.472, 5.224, 4.416, 6.212, respectively; 95% confidence interval 2.123 to 9.721, 1.632 to 7.427, 3.325 to 10.211, 2.321 to 9.322, 4.127 to 13.782, 2.561 to 9.418, 1.322 to 6.289, 3.315 to 11.526, 2.213 to 9.382, 4.474 to 13.541; all P<0.05). The predictive power of preoperative SII (AUC=0.842, 0.815) and pathological TNM stage (AUC=0.881, 0.827) for the 5-year overall survival and disease-free survival of patients with gastric cancer after radical resection was similar, however the predictive power of combination of the two (AUC=0.943, 0.895) was higher than that of preoperative SII and pathological TNM stage alone. Conclusions:Preoperative SII is an independent risk factor for the prognosis of patients with gastric cancer after radical resection, combined with parthological TNM stage can be used as an indicator to predict the prognosis and recurrence of patients.

3.
Article in Chinese | WPRIM | ID: wpr-911584

ABSTRACT

Objective:To explore the risk factors of lymphatic fistula after radical gastric cancer operation.Methods:We retrospectively analyze the clinicopathological data of gastric cancer patients who underwent radical surgery from May, 2019 to May, 2020 at the Third Department of Surgery, Fourth Hospital of Hebei Medical University, and analyze the risk factors impacting postoperative lymphatic leakage,for the establishment of the risk prediction scoring model.Results:A total of 487 patients with gastric cancer underwent radical gastrectomy, of which 32 patients (6.6%) had lymphatic leakage . Multivariate logistic regression analysis showed that hypoproteinemia before surgery (95% CI: 1.222-7.357, P=0.016), the lesion is located in the cardia-fundus of the stomach (95% CI: 1.117-6.788, P=0.028),stage T3-T4 (95% CI: 1.149-25.676, P=0.033), operation time ≥4 h (95% CI: 1.469-11.480, P=0.007), combined organ resection (95% CI: 1.106-12.886, P=0.034), D2+ lymph node dissection (95% CI: 1.969-11.510, P=0.001), anemia (95% CI: 1.271-9.392, P=0.015) were an independent risk factors. Equation based on multi-factor Logistic regression: logit( P)=-9.624+1.098×X 1+1.013×X 2+1.692×X 3+1.413×X 4+1.328×X 5+1.560×X 6+1.240×X 7 was estaslished, using Hosmer. Lemeshow test detects the goodness of fit of the regression equation ( P=0.348). The area under the ROC curve was 0.856 (95% CI: 0.787-0.926, P<0.001); the probability of lymphatic leakage when scores ≥4 points was 14.1%, when scores <4 points ,the probability of leakage was 2.5%. Conclusion:A risk prediction scoring model for lymphatic leakage after radical gastrectomy, can identify patients with high risk after surgery

4.
Article in Chinese | WPRIM | ID: wpr-910450

ABSTRACT

Objective:To summarize the experience of ELEKTA Unity MR-linac in clinical application in our hospital and analyze the positioning accuracy, process time and other related issues.Methods:A total of 14 patients enrolled in the Unity MR-Linac study were reviewed. All treatment time (including positioning, scanning, replanning, and beam discharge) and setup errors in 3directions were statistically analyzed. 11 patients with conventional accelerators using the multifunctional immobilization system (MIS) were randomly selected to make statistical analysis of the setup errors, and the differences between the Unity group and the conventional accelerators using the MIS were compared using t-test. Results:In the Unity group, the setup errors in X, Y and Z directions were (-0.15±0.30) cm, (0.02±0.57) cm and (-0.10±0.28) cm, respectively. The average treatment time was 36.87minutes. The average positioning time was 5.40minutes. The mean scan time was 7.48minutes, the mean adaptive plan time was 7.46minutes, and the mean beam time was 9.48minutes. In the conventional accelerator group, the setup errors were (0.05±0.25) cm, (-0.01±0.25) cm and (-0.03±0.23) cm, respectively. The results of the setup errors of patients fixed with MIS showed that there were significant differences in the left and right directions ( P<0.001), while there were no significant differences in the Y and Z directions ( P=0.061 and 0.374) between two groups. Conclusions:Except in the X direction, there is no significant difference in setup errors between the Unity and conventional accelerator groups in the condition of laser-free system. Under smooth circumstances, the treatment time by using ATP (adapt to position) workflow will also be within the range of tolerance of the patients. Magnetic-guided radiotherapy has a promising application prospect, whereas the procedure needs to be optimized.

5.
Article in Chinese | WPRIM | ID: wpr-908422

ABSTRACT

Objective:To investigate the application value of individualized full-course nutritional intervention in neoadjuvant concurrent chemoradiotherapy (nCRT) for locally advanced Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The perspec-tive randomized control study was conducted. The clinicopathological data of 90 patients with locally advanced Siewert type Ⅱ and Ⅲ AEG who underwent nCRT in the Fourth Hospital of Hebei Medical University from February 2012 to December 2018 were selected. Patient were divided into two groups with 1:1 according to random number table. Patients undergoing nCRT combined with individualized full-course nutritional intervention were allocated into experimental group, and patients undergoing nCRT combined with common nutritional intervention were allocated into control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period; (3) efficacy evaluation and adverse effects of nCRT; (4) surgical and recovery situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement date with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Grouping situations of the enrolled patients: a total of 90 patients were selected for eligibility. There were 77 males and 13 females, aged from 26 to 74 years, with a median age of 62 years. Of 90 patients, there were 45 cases in the experimental group and 45 cases in the control group. (2) Changing situations of nutritional status and quality of life of patients in nCRT and preoperative waiting period: ① during the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the body mass was (67±10)kg, (66±9)kg, (67±10)kg, (68±10)kg, (70±10)kg for the experi-mental group, respectively, and (65±9)kg, (59±8)kg, (62±8)kg, (64±8)kg, (66±9)kg for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the body mass ( χ2=195.010, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of body mass changing between the two groups ( F=93.974, 60.638, 4.144, P<0.05). ② During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the total protein was (66±4)g/L, (65±4)g/L, (65±4)g/L, (68±4)g/L, (71±5)g/L for the experimental group, respectively, and (65±4)g/L, (62±5)g/L, (63±5)g/L, (65±5)g/L, (67±6)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the total protein ( χ2=652.524, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of total protein changing between the two groups ( F=672.507, 6.424, 5.057, P<0.05). ③ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the albumin was (40±3)g/L, (38±4)g/L, (38±4)g/L, (39±4)g/L, (40±4)g/L for the experimental group, respectively, and (39±4)g/L, (35±5)g/L, (36±4)g/L, (36±4)g/L, (37±5)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the albumin ( χ2=289.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of albumin changing between the two groups ( F=4 210.683, 5.013, 7.330, P<0.05). ④ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the prealbumin was (228±41)mg/L, (222±56)mg/L, (223±47)mg/L, (227±46)mg/L, (233±53)mg/L for the experimental group, respectively, and (202±49)mg/L, (174±68)mg/L, (179±54)mg/L, (185±51)mg/L, (193±57)mg/L for the control group. The multi-variate test was conducted based on the mauchly's test of sphericity for the prealbumin ( χ2=297.324, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of prealbumin changing between the two groups ( F=871.545, 6.111, 14.426, P<0.05). ⑤ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the hemoglobin was (124±14)g/L, (121±14)g/L, (125±13)g/L, (127±13)g/L, (128±13)g/L for the experimental group, respectively, and (121±18)g/L, (114±14)g/L, (116±14)g/L, (117±16)g/L, (118±22)g/L for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the hemoglobin ( χ2=257.560, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of hemoglobin changing between the two groups ( F=2 533.553, 4.142, 4.985, P<0.05). ⑥ During the nCRT treatment (week 3, week 6) and the preopera-tive waiting period (week 9, week 12, week 15), the patient-generated subjective global assessment (PG-SGA) score was 4.4±1.2,6.3±1.4, 5.5±1.4, 4.3±1.4, 3.4±1.7 for the experimental group, respec-tively, and 4.9±1.2, 7.4±1.7, 7.3±1.6, 6.3±1.4, 6.0±1.5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the PG-SGA score ( χ2=289.543, P<0.05). There were significant differences in the time effect, interaction effect, intervention effect of PG-SGA score changing between the two groups ( F=648.583, 41.906, 26.098, P<0.05). ⑦ During the nCRT treatment (week 3, week 6) and the preoperative waiting period (week 9, week 12, week 15), the quality of life questionnaire of stomach (QLQ-ST022) score was 13±3, 16±6, 16±4, 14±4, 12±5 for the experimental group, respectively, and 15±4, 21±6, 20±4, 17±4, 15±5 for the control group. The multivariate test was conducted based on the mauchly's test of sphericity for the QLQ-STO22 ( χ2=279.865, P<0.05). There were significant differences in the time effect, interaction effect, interven-tion effect of QLQ-STO22 changing between the two groups ( F=710.238, 7.261, 16.794, P<0.05). (3) Efficacy evaluation and adverse effects of nCRT: there were 25 patients and 20 cases of the experimental group with partial response and stable disease, showing the objective response rate and disease control rate as 55.6%(25/45)and 100.0%(45/45). There were 18 patients and 27 cases of the control group with partial response and stable disease, showing the objective response rate and disease control rate as 40.0%(18/45)and 100.0%(45/45). There was no significant difference in the nCRT efficacy between the two groups ( P>0.05). Cases with leukopenia, neutropenia, anemia, nausea, and loss of appetite were 27, 25, 19, 30, 34 for the experimental group, versus 37, 34, 29, 39, 42 for the control group, showing significant differences between the two groups ( χ2=5.409, 3.986, 4.464, 5.031, 5.414, P<0.05). (4) Surgical and recovery situations: patients of the experimental group underwent surgeries successfully. Two patients of the control group diagnosed with peritoneal metastasis after laparoscopic exploration underwent conversion therapy and no surgery, the other 43 patients underwent surgeries. The time to postoperative gastric tube removal, time to postopera-tive drainage tube removal, time to postoperative first flatus, time to postoperative first defecation, duration of postoperative hospital stay were 2.0 days (1.5 days, 3.0 days), 6.0 days (5.0 days,11.0 days), 2.0 days (1.5 days, 2.5 days), 2.0 days (1.5 days, 2.5 days), 7.0 days (6.0 days,14.0 days) for the experimental group, versus 3.0 days (2.0 days,4.0 days), 7.0 days (5.5 days,14.0 days), 2.0 days (1.5 days,3.0 days), 3.0 days (2.0 days,3.5 days), 8.0 days (6.0 days, 17.0 days) for the control group, showing significant differences between the two groups ( Z=-3.477, -4.398, -3.068, -5.786, -3.395, P<0.05). Conclusion:For AEG patients undergoing nCRT, the individualized full-course nutrition intervention involving nutritionists is beneficial to improve the nutritional status, reduce adverse reactions, and improve the quality of life of the patients, promote postoperative short-term recovery. Registry: this study was registered at clinicaltrials.gov in United States, with the registry number of NCT01962246.

6.
Article in Chinese | WPRIM | ID: wpr-908063

ABSTRACT

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

7.
China Pharmacy ; (12): 2924-2929, 2021.
Article in Chinese | WPRIM | ID: wpr-906663

ABSTRACT

OBJECTIVE:To improve the level of pharmaceutical care,enhance the professional value and social status of pharmacists by clarifying the development process of pharmaceutical care and summarizing the value of pharmacists in pharmaceutical care. METHODS:The development process of pharmaceutical care at home and abroad(service objects,service contents and service methods)was summarized;the current situation of pharmaceutical care in China was analyzed;the value of pharmaceutical care were defined in respects of rational drug use,humanistic value and medical resources. The development of pharmaceutical care in the future was prospected. RESULTS & CONCLUSIONS:The development of pharmaceutical care can be divided into three stages:“drug supply as the center”“promoting rational drug use as the center”and“patients as the center”,and the service objects,service contents and service methods in different stages are expanding and diversifying. Compared with developed countries,the overall level of pharmaceutical care in China lags behind,and there are differences in level of pharmaceutical care modes in hospitals at different levels. Pharmacists ensure the safety,effectiveness and economy of drug use through pharmaceutical care,and promote rational drug use;the compliance,quality of life and satisfaction of patients have been improved through pharmaceutical care;pharmacists participate in medical quality management to save medical and health resources through pharmaceutical care. Pharmaceutical care,as an important part of the medical and health system,plays an important and irreplaceable role in the medical process,which is suggested that the relevant government departments should fully understand the value of pharmaceutical care and further strengthen their support for pharmaceutical care;pharmaceutical staff should improve their self-cultivation and cooperate with other disciplines to achieve the sustainable development of hospital pharmacy in different regions and medical institutions.

8.
Article in Chinese | WPRIM | ID: wpr-904623

ABSTRACT

Objective To investigate the changes of mitochondrial metabolic functions of macrophages following Echinococcus multilocularis infections, so as to provide insights into the pathogenesis of alveolar echinococcosis. Methods Two groups were assigned according to different treatment methods. In the culture group, mouse leukemic monocyte macrophage RAW264.7 cells were cultured with 2 000 E. multilocularis at a ratio of 500∶1, while RAW264.7 cells in the control group were given no treatment. Then, both the culture and control groups were further divided into the 24 h and 72 h subgroups. Mitochondria were stained with MitoTracker® Deep Red FM and the mean fluorescence intensity of macrophage mitochondria was measured with the Cytation 5 Cell Imaging Multi-Mode Reader. The mitochondrial DNA copy number was quantified using the quantitative real-time PCR (qPCR) assay, and the mitochondrial energy metabolism was monitored using the Seahorse XF assay. In addition, the mitochondrial reactive oxygen species and mitochondrial membrane potential were detected using flow cytometry. Results The mean fluorescence intensities of macrophage mitochondria were significantly lower in the 24 h (15 341 ± 2 532 vs. 17 823 ± 3 429; t = 6.379, P < 0.01) and 72 h (18 102 ± 3 505 vs. 21 511 ± 5 144; t = 17.680, P < 0.01) culture subgroups than in the corresponding control subgroups, and lower mitochondrial DNA copy numbers were measured in the 72 h culture subgroup than in the 72 h control group [(3.23 × 109 ± 1.78 × 107) vs. (4.39 × 109 ± 3.70 × 107); t = 8.85, P < 0.001]. The oxygen consumption rates were significantly greater in the 24 h [(241.70 ± 73.13) pmol/min vs. (69.05 ± 52.30) pmol/min; t = 7.89, P < 0.01] and 48 h culture groups [(249.50 ± 42.06) pmol/min vs. (60.28 ± 40.66) pmol/min; t = 8.64, P < 0.01] than in the corresponding control groups, and a higher extracellular acidification rate was seen in the 48 h culture group than in the 48 h control group ([ 111.6 ± 17.49) mpH/min vs. (35.05 ± 7.57) mpH/min; t = 16.90, P < 0.01]. In addition, flow cytometry detected higher mean fluorescence intensity of mitochondrial reactive oxygen species (58 264 ± 10 087 vs. 4 307 ± 97; t = 12.930, P < 0.01) and lower mitochondrial membrane potential (9.833% ± 2.285% vs. 2.667% ± 0.208%; t = 6.645, P < 0.01) in the 72 h culture group than in the control group. Conclusions E. multilocularis infection may impair mitochondrial functions and inhibit oxidative phosphorylation of macrophages, resulting in increased macrophage glycolysis. It is speculated that the alteration of macrophage metabolic states may contribute to the mechanisms underlying the development and progression of alveolar echinococcosis.

9.
Acta Pharmaceutica Sinica B ; (6): 763-780, 2021.
Article in English | WPRIM | ID: wpr-881168

ABSTRACT

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

10.
Journal of Clinical Hepatology ; (12): 1806-1810., 2021.
Article in Chinese | WPRIM | ID: wpr-886335

ABSTRACT

ObjectiveTo establish a droplet digital PCR (ddPCR) method for detecting hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). MethodsHBV cccDNA standard substance was constructed, and HBV cccDNA primers and probes were designed based on the structural differences between HBV cccDNA and relaxed circular DNA (rcDNA). HBV plasmid was amplified to obtain HBV cccDNA standard substance, and a ddPCR detection method was established with the standard substance after gradient dilution as the template for HBV cccDNA detection; the limit of detection and repeatability of this method were analyzed. Liver tissue samples were collected from 20 patients who attended Beijing YouAn Hospital, Capital Medical University, from June 2017 to October 2020, all of whom were diagnosed with HBV infection, and DNA of the samples was extracted and digested with plasmid-safe ATP-dependent DNA enzyme to obtain HBV cccDNA template; the ddPCR detection method was evaluated in clinical samples and was compared with the quantitative real-time PCR (qPCR) detection method. The chi-square test was used for comparison of categorical data between the two groups. ResultsThe HBV cccDNA detection method based on ddPCR was established, which accurately detected HBV cccDNA in standard substance after gradient dilution, with a limit of detection of 1 copy/μl, and the coefficients of variation of 1×103, 1×102, and 1×101 copies/μl standard substances were 441%, 3.98%, and 5.09%, respectively. HBV cccDNA was detected in the samples of 20 patients with HBV infection; the ddPCR detection method detected HBV cccDNA in 17 patients, with a positive rate of 85%, while the qPCR detection method detected HBV cccDNA in 11 patients, with a positive rate of 55%, and there was a significant difference between the two methods (χ2=4.286, P=0038). ConclusionThe established ddPCR method for detecting HBV cccDNA has a low limit of detection and good repeatability, which provides an effective tool for further clinical detection.

11.
Cancer Research and Clinic ; (6): 104-108, 2021.
Article in Chinese | WPRIM | ID: wpr-886016

ABSTRACT

Objective:To investigate the risk factors of pancreatic fistula after radical resection of gastric cancer, and to establish a risk prediction scoring model for pancreatic fistula.Methods:The clinico-pathological data of 312 patients with gastric cancer admitted to the Fourth Hospital of Hebei Medical University from January 2019 to January 2020 were retrospectively analyzed. Multiple factor logistic regression model was used to analyze the risk factors of pancreatic fistula after radical resection of gastric cancer, and a risk prediction scoring model based on the risk factors was established. Hosmer-Lemeshow test was used to detect the goodness of fit of regression equation, and receiver operating characteristics (ROC) curve was used to evaluate the distinction degree of regression equation.Results:Among 312 patients with gastric cancer, 27 cases (8.65%) had pancreatic fistula after radical resection of gastric cancer. Multiple factor logistic regression analysis showed that male patients ( OR = 5.312, 95% CI 1.532-18.420, P = 0.008), age ≥ 60 years old ( OR = 4.928, 95% CI 1.493-16.250, P = 0.009), preoperative diabetes mellitus ( OR = 3.062, 95% CI 1.091-8.589, P = 0.034), lesion location in the gastric body-gastric antrum ( OR = 3.121, 95% CI 1.052-9.251, P = 0.040), intraoperative omental bursa resection ( OR = 6.209, 95% CI 2.084-18.478, P = 0.001), intraoperative lymph node dissection at D2+ station ( OR = 3.114, 95% CI 1.044-9.281, P = 0.042), intraoperative combined organ resection ( OR = 5.063, 95% CI 1.473-17.400, P = 0.010), preoperative TNM stage Ⅲ ( OR = 4.973, 95% CI 1.189-20.792, P = 0.028) were independent risk factors for pancreatic fistula after radical resection of gastric cancer. A risk prediction equation of pancreatic fistula after radical resection of patients with gastric cancer was established: P = -8.619+1.670X 1+1.595X 2+1.119X 3+1.138X 4+1.826X 5+1.136X 6+1.622X 7+1.604X 8; factor X was set as a binomial assignment (0 or 1); X1-X8 were listed as follows respectively: gender (the male was 1), age (≥60 years old was 1), preoperative diabetes history (yes was 1), lesion location (gastric body-gastric antrum was 1), intraoperative resection of omental bursa or not (yes was 1), intraoperative lymph node dissection at D2+ station or not (yes was 1), intraoperative combined organ resection or not (yes was 1), preoperative TNM stage (stage Ⅲ was 1). The goodness of fit of regression equation was high ( P = 0.395). The area under the curve of ROC by using risk prediction scoring model to judge pancreatic fistula was 0.916 (95% CI 0.872-0.960, P<0.01). The probability of pancreatic fistula in patients with score ≥ 5 was 40.90%, and the probability of pancreatic fistula in patients with score < 5 was 3.35%. Conclusions:The occurrence of pancreatic fistula after radical resection of gastric cancer is closely related to a variety of risk factors. By establishing a risk prediction scoring model for pancreatic fistula after radical resection of gastric cancer, it is helpful to effectively identify patients with high risk of pancreatic fistula after radical surgery during the perioperative period.

12.
Article in Chinese | WPRIM | ID: wpr-885280

ABSTRACT

Objective:To investigate the clinically relevant factors of progressive disease (PD) after neoadjuvant therapy for locally advanced gastric cancer.Methods:From Jun 2011 to Mar 2016, 569 patients with locally advanced gastric cancer(cT3/4N0/+ M0) admitted to the Fourth Hospital of Hebei Medical University were retrospectively analyzed .Results:All 569 patients completed neoadjuvant therapy, 59 patients (10.4%) had PD. Univariate analysis showed that tumor size (χ 2=10.091, P=0.001), pathological type (χ 2=4.110, P=0.043), Borrmann type (χ 2=91.941, P=0.001), pre-treatment cT stage (χ 2=7.980, P=0.005) were associated with PD after neoadjuvant therapy for gastric cancer. The results of multi-factor regression analysis showed that pathological type, Borrmann type, pre-treatment cT stage were independent factors influencing the occurrence of PD after neoadjuvant therapy for advanced gastric cancer. The overall survival and progression-free suruival time of patients with PD is significantly shorter than that of patients without PD . Conclusion:The pathological type, Borrmann typing and pre-treatment cT stage are the influencing factors for the occurrence of PD after neoadjuvant treatment in advanced gastric cancer, and the prognosis of PD patients is poor.

13.
Chinese Journal of Geriatrics ; (12): 96-101, 2021.
Article in Chinese | WPRIM | ID: wpr-884849

ABSTRACT

Objective:To explore the clinico-pathological characteristics and risk factors affecting prognosis in elderly patients with gastric cancer.Methods:A retrospective study was used to retrospectively analyze 2386 patients with gastric cancer undergoing radical surgery in Surgery Department of the Fourth Hospital of Hebei Medical University from 1 January 2012 to 1 January 2015.Patients aged 70 years and older were screened so as to analyze clinical characteristics and influencing factors for the prognosis.Results:A total of 2386 patients with gastric cancer were divided into the elderly group aged 70 years and older(342 of 2386 cases, 14.3%). There were statistically significant differences between the two groups in gender, number of concomitant diseases, NRS2002 score, PG-SGA score, tumor location, tumor diameter, histological type, Borrmann classification, tumor invasion depth staging(pT), lymph node metastasis staging(pN), the anatomic extent of tumor staging(TNM, pTNM), and Lauren classifications( P<0.05). The 981 of 2386 cases(41.4%)had postoperative complications, accompanied by 413 cases(17.3%)of surgery-related complications and 568 cases(24.0%)of non-surgery-related complications.A multivariate logistic analysis showed that the number of preoperative co-existing diseases ≥ 2 was an independent influencing factor for postoperative complications in elderly gastric cancer patients( HR=4.478, 95% CI: 1.121-7.918, P=0.006). The 5-year OS and DSS was 21.10% and 62.73% in the ≥70 years gastric cancer group, and was 54.1% and 70.0% in the <70 years gastric cancer group, respectively.The difference in the 5-year OS between the two groups was statistically significant( P<0.05), while the difference in the 5-year DSS between the two groups was not statistically significant( P>0.05). Multivariate analysis by the Cox proportional hazard model showed that the independent risk factors for the prognosis of elderly patients with gastric cancer included the low-undifferentiated histological type of the tumor( P=0.004), the depth of tumor invasion pT stage of pT4a-pT4b( P=0.007), lymph node metastasis( P=0.034), tumor pTNM stage ⅢA-ⅢC( P=0.002)and vascular tumor thrombus( P=0.034). Conclusions:Elderly patients with gastric cancer have many preoperative co-existing diseases, which increases the risk of postoperative non-surgical complications.Therefore, we should focus on the peri-operative management of their comorbid diseases so as to improve the safety and efficacy of surgery.The advanced age is not the independent risk factors for the prognosis.

14.
Chinese Journal of Orthopaedics ; (12): 633-643, 2021.
Article in Chinese | WPRIM | ID: wpr-884754

ABSTRACT

Objective:To investigate the effects of allicin on the proliferation, migration and angiogenesis of rat vascular endothelial cells (RVES), and to explore the influencing mechanism of allicin on epidural fibrosis.Methods:According to the results of preliminary experiments, RVECs were divided into control group (0 mg/L), low concentration group (25 mg/L), medium concentration group (50 mg/L) and high concentration group (100 mg/L). The morphology, viability, migration rate, cell cycle, apoptosis rate and cell lumen formation ability were measured using fluorescence microscope, AnnexinV-FITC double staining, PI/RN-asestaining, scratch assay and Transwell experiments test. Western Blot was used to measure the protein expression level of JAK2, STAT3, p-STAT3, PCNA, Bax and Bcl-2 protein. Using random number method, 36 adult male SD rats were divided into sham operation group, saline group and allicin group, with 12 rats in each group. Hematoxylin-eosin (HE) staining, Masson staining and immunohistochemical staining were used to analysis the epidural fibrosis in each group.Results:With the increase of concentration of allicin, cell viability, cell migration and lumen formation ability significantly lower than that of control group ( P<0.05). With the increase of allicin concentration, the percentage of cells in the G1 and S phases gradually decreased ( P<0.05), the percentage of cells in the G2 phase and the apoptosis rate gradually increased ( P<0.05), and the cells were blocked in the G2/M phase. With the increase of allicin concentration, the protein expression levels of JAK2, STAT3, p-STAT3, PCNA and Bcl-2 were gradually down-regulated ( P<0.05), while the protein expression level of Bax was gradually up-regulated ( P<0.05), the ratio of p-STAT3/STAT3 was decreased ( P<0.05), and the ratio of Bax/Bcl-2 was increased ( P<0.05). There was no death, infection or abnormal gait in all the experimental animals. Dense scar tissue could be observed in the extradural area of the sham operation group and the epidural area of the control group, but there was obvious space between the epidural scar and the dura mater in the allicin group, and the density of collagen, the number of blood vessels, and the protein density of p-STAT3 were significantly lower than those in the control group ( P<0.05). Conclusion:Allicin inhibits angiogenesis and the severity of epidural scar after laminectomy, and the mechanism may be through inhibiting the JAK2/STAT3 signaling pathway of vascular endothelial cells.

15.
Article in Chinese | WPRIM | ID: wpr-882628

ABSTRACT

Objective:To investigate the effect of Qingre-Tongfu enema combined with noninvasive positive pressure ventilation on the ventilation function of elderly patients with severe pneumonia. Methods:A total of 60 elderly patients with severe pneumonia with syndrome of excess of Yangming fushi from September 2017 to August 2019 in the respiratory department of the First People’s Hospital of Dongcheng District, Beijing were randomly divided into two groups, 30 cases in each group. The control group was treated with western medicine to control infection and noninvasive positive pressure ventilation. The treatment group was treated with Qingre-Tongfu enema on the basis of the control group. The Traditional Chinese Medicine Syndrome score (TCMSSS), Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE-Ⅱ) and Clinical Pulmonary Infection Score (CPIS) were compared before and after treatment, The Pneumonia Severity Index (PSI) was compared. Serum procalcitonin (PCT) was detected by upconversion luminescence immunoassay, CRP was detected by double antibody sandwich ELISA, WBC was detected by automatic hematology analyzer; partial pressure of carbon dioxide (PaCO 2), oxygen saturation (SaO 2), partial pressure of oxygen (PaO 2) were detected by blood gas analyzer, oxygenation index (OI) and respiratory rate (RR) were calculated. The complications were investigated and the clinical efficacy was evaluated. Results:The total effective rate was 96.7% (29/30) in the treatment group and 73.3% (22/30) in the control group, with significant difference between the two groups ( χ2=4.706, P=0.030). After treatment, the levels of serum PCT, CRP and WBC in the treatment group were significantly lower than those in the control group ( t=15.359, 25.784 and 13.460, respectively, P<0.01); after treatment, the levels of SaO 2 [(93.18 ± 3.79)% vs. (88.78 ± 5.56)%, t=3.584], PaO 2 [(86.81 ± 4.01) mmHg vs. (80.01 ± 4.76) mmHg, t=5.975], OI [(285.53 ± 15.05) mmHg vs. (227.65 ± 12.37) mmHg, t=16.272] in the treatment group significantly were higher than those in the control group ( P<0.01); PaCO 2 [(43.28 ± 6.84) mmHg vs. (48.83 ± 7.66) mmHg, t=-2.956], RR [(22.00 ± 3.79) times/min vs. (26.30 ± 3.73) times/min, t=-4.434] in the treatment group were significantly lower than those in the control group ( P<0.05). After treatment, the scores of TCMSSS, APACHE-Ⅱ, CPIS and PSI in the treatment group were significantly lower than those in the control group ( t=41.310, 11.035, 8.399, 5.752, P<0.01). The treatment group in the course of antibiotics, mechanical ventilation time, hospital stay were significantly shorter than the control group ( P<0.01). Conclusion:Qingre-Tongfu enema combined with noninvasive positive pressure ventilation can improve the clinical symptoms of elderly patients with severe pneumonia, reduce inflammatory reaction, shorten the time of mechanical ventilation and antibiotic treatment, and improve the clinical efficacy.

16.
Article in English | WPRIM | ID: wpr-880866

ABSTRACT

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.


Subject(s)
Cancer-Associated Fibroblasts/metabolism , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glycolysis , Head and Neck Neoplasms , Humans , MicroRNAs/metabolism , Mouth Neoplasms/genetics , Phosphofructokinase-2/genetics , RNA, Long Noncoding/genetics , Signal Transduction , Tumor Microenvironment
17.
Chinese Journal of Lung Cancer ; (12): 108-111, 2021.
Article in Chinese | WPRIM | ID: wpr-880248

ABSTRACT

BACKGROUND@#Lung cancer is the highest incidence of cancer in the world, which seriously threatens human health. Early diagnosis and treatment of lung cancer is particularly important for the survival of lung cancer patients. Serum tumor markers have been widely used as an important method for early diagnosis of tumor. However, there are few early diagnostic markers for lung cancer. Therefore, the aim of this study was to investigate the expression level of Lipocalin-2 and its clinical significance in serum of patients with lung cancer.@*METHODS@#The serum levels of Lipocalin-2 in 60 lung cancer patients and 63 healthy people were detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between the expression level of Lipocalin-2 and the clinical characteristics of lung cancer was analyzed.@*RESULTS@#The expression level of Lipocalin-2 in peripheral blood serum of patients with lung cancer was significantly higher than that of healthy people, and the difference was statistically significant (P<0.001). The expression of Lipocalin-2 in patients with lung cancer was related to the differentiation, stage and lymph node metastasis of pathological tissues, and the difference was statistically significant (P<0.05). The expression level of Lipocalin-2 in serum of patients with poorly differentiated lung cancer was higher than that of patients with well differentiated lung cancer; the expression level of Lipocalin-2 in serum of patients with lymph node metastasis was higher than that of patients without lymph node metastasis; the expression level of Lipocalin-2 in patients with clinical stage III + IV lung cancer was significantly higher than that of patients with clinical stage I + II lung cancer, and the differences were statistically significant (P<0.05).@*CONCLUSIONS@#Lipocalin-2 is highly expressed in serum of patients with lung cancer, which is related to pathological differentiation, stage and lymph node metastasis. It is expected to become a potential new tumor marker for clinical diagnosis of lung cancer.

18.
Article in English | WPRIM | ID: wpr-879675

ABSTRACT

Throughout the past 2020, the pandemic COVID-19 has caused a big global shock, meanwhile it brought a great impact on the public health network. Trauma emergency system faced a giant challenge and how to manage trauma under the pandemic of COVID-19 was widely discussed. However, the trauma treatment of special population (geriatric patients and patients taking anticoagulant drugs) has received inadequate attention. Due to the high mortality following severe traumatic hemorrhage, hemostasis and trauma-induced coagulopathy are the important concerns in trauma treatment. Sepsis is another topic should not be ignored when we talking about trauma. COVID-19 itself is a special kind of sepsis, and it may even be called as serious systemic infection syndrome. Sepsis has been become a serious problem waiting to be solved urgently no matter in the fields of trauma, or in intensive care and infection, etc. This article reviewed the research progress in areas including trauma emergency care, trauma bleeding and coagulation, geriatric trauma and basic research of trauma within 2020.


Subject(s)
COVID-19 , Community Networks , Disseminated Intravascular Coagulation/therapy , Emergency Medical Services , Female , Health Services for the Aged , Hemorrhage/therapy , Hemostasis , Humans , Male , Pandemics , Public Health , Sepsis/therapy , Time Factors , Trauma Centers , Wounds and Injuries/therapy
19.
Article in English | WPRIM | ID: wpr-879664

ABSTRACT

The year 2020 is an extremely unusual year. The world lost more than one million lives due to the attack of COVID-19. Economic production has been greatly reduced, and daily activities are largely restricted. Luckily the work of Chinese Journal of Traumatology (CJTEE) has not been adversely affected. 2020 is a harvest year for the journal, which (1) was included in the high-quality academic journals by China Association for Science and Technology; (2) cover of each issue is newly designed; (3) submission increased by about 60% with more countries and regions covered; (4) usage in the ScienceDirect database exceeded a million; (5) the CiteScore rises to more than 2.0 the first time. This study reviewed the articles published in the year 2020 by CJTEE.


Subject(s)
COVID-19 , China , Humans , Periodicals as Topic , Science/organization & administration , Societies, Scientific/organization & administration , Technology/organization & administration , Time Factors , Traumatology/organization & administration , Wounds and Injuries/etiology
20.
Chinese Medical Journal ; (24): 2061-2070, 2020.
Article in English | WPRIM | ID: wpr-826420

ABSTRACT

BACKGROUND@#The effects of oral contrast agents (OCAs) on dosimetry have not been studied in detail. Therefore, this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer.@*METHODS@#From 2008 to 2016, computed tomography (CT) images were obtained from 33 rectal cancer patients administered OCA with or without intravenous contrast agent (ICA) and 14 patients who received no contrast agent. CT numbers of organs at risk were recorded and converted to electronic densities. Volumetric-modulated arc therapy plans were designed before and after the original densities were replaced with non-enhanced densities. Doses to the planned target volume (PTV) and organs at risk were compared between the plans.@*RESULTS@#OCA significantly increased the mean and maximum densities of the bowels, while the effects of ICA on these parameters depended on the blood supply of the organs. With OCA, the actual doses for PTV were significantly higher than planned and doses to the bowel increased significantly although moderately. However, the increase in the volume receiving a high-range doses was substantial (the absolute change of intestine volume receiving ≥52 Gy: 1.46 [0.05-3.99, cubic centimeter range: -6.74 to 128.12], the absolute change of colon volume receiving ≥50 Gy: 0.34 [0.01-1.53 cc, range: -0.08 to 3.80 cc]. Dose changes due to ICA were insignificant. Pearson correlation showed that dose changes were significantly correlated with a high intestinal volume within or near the PTV (ρ > 0.5, P  0.3, P < 0.05).@*CONCLUSIONS@#Contrast agents applied in simulation cause underestimation of doses in actual treatment. The overdose due to ICA was slight, while that due to OCA was moderate. The bowel volume receiving ≥50Gy was dramatically increased when OCA within the bowel was absent. Physicians should be aware of these issues if the original plan is barely within clinical tolerance or if a considerable volume of enhanced intestine is within or near the PTV.

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