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Objective:To establish and validate a preoperative differentiateon model of intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular carcinoma (CHC) based on the inflammatory markers and conventional clinical indicators.Methods:The clinical data of 116 patients with ICC or CHC admitted to Henan Provincial People's Hospital from January 2018 to March 2023 were retrospectively analyzed, including 74 males and 42 females, aged (58.5±9.4) years old. The data of 83 patients were used to establish the differentiation model as the training group, including 50 cases of ICC and 33 cases of CHC. The data of 33 patients were used to validate the model as the validation group, including 20 cases of ICC and 13 cases of CHC. The clinical data including the platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), prognostic inflammatory index (PII), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were collected and analyzed. The receiver operating characteristic (ROC) curve was used to analyze the best cut-off values of PLR, SII, PII, PNI, NLR and LMR. Univariate and multivariate logistic regression analysis were used to determine the differential factors between ICC and CHC. The R software was used to draw the nomogram, calculate the area under the curve (AUC) to evaluate the model accuracy, and draw the calibration chart and the decision curve to evaluate the predictive efficacy of the model.Results:Univariate logistic regression analysis showed that liver cirrhosis, history of hepatitis, alpha fetoprotein, carbohydrate antigen 199, gamma-glutamyltransferase (GGT), PLR, PNI and inflammation score (IS) could be used to differentiate ICC from CHC (all P<0.05). The indicators identified in univariate analysis were included in multivariate logistic regression analysis. The results showed that absence of liver cirrhosis, GGT>60 U/L, PNI>49.53, and IS<2 indicated the pathology of ICC (all P<0.05). Based on the above four factors, a nomogram model was established to differentiate the ICC and CHC. The AUC of ROC curve of the nomogram model in the training and validation groups were 0.851 (95% CI: 0.769-0.933) and 0.771 (95% CI: 0.594-0.949), respectively. The sensitivities were 0.760 and 0.750, and the specificities were 0.818 and 0.769, respectively. The calibration chart showed that the predicted curve fitted well to the reference line. The decision curve showed that the model has a clear positive net benefit. Conclusion:The nomogram model based on inflammatory markers showed a good differentiation performance of ICC and CHC, which could benefits the individualized treatment.
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Objective:To construct a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma (ICC) based on the albumin-bilirubin index (ALBI), and to evaluate its predictive efficacy.Methods:From January 2016 to January 2020, 170 patients with ICC who underwent radical surgical resection at the People's Hospital of Zhengzhou University were retrospectively analyzed. There were 90 males and 80 females, aged (58.5±10.6) years old. Based on a ratio of 7∶3 by the random number table, the patients were divided into the training set ( n=117) and the internal validation set ( n=53). The training set was used for nomogram model construction, and the validation set was used for model validation and evaluation. Follow up was conducted through outpatient reexamination and telephone contact. The Kaplan-Meier method was used for survival analysis, and a nomogram was drawn based on variables with a P<0.05 in multivariate Cox regression analysis. The predictive strength of the predictive model was evaluated by analyzing the consistency index (C-index), calibration curve, and clinical decision curve of the training and validation sets. Results:Multivariate Cox regression analysis showed that carbohydrate antigen 19-9 (CA19-9) ≥37 U/ml ( HR=1.99, 95% CI: 1.10-3.60, P=0.024), ALBI≥-2.80 ( HR=2.43, 95% CI: 1.40-4.22, P=0.002), vascular tumor thrombus ( HR=2.34, 95% CI: 1.40-3.92, P=0.001), and the 8th edition AJCC N1 staging ( HR=2.18, 95% CI: 1.21-3.95, P=0.010) were independent risk factors affecting postoperative survival of ICC patients after curative resection. The predictive model constructed based on the above variables was then evaluated, and the C-index of the model was 0.76. Calibration curve showed the predicted survival curve of ICC patients at 3 years after surgery based on the model was well-fitted to the 45° diagonal line which represented actual survival. Clinical decision curve analysis showed that the model had a significant positive net benefit in both the training and validation sets. Conclusion:The nomograph model for survival rate after radical resection of ICC was constructed based on four variables: ALBI, CA19-9, vascular tumor thrombus, and AJCC N staging (8th edition) in this study. This model provided a reference for more accurate prognosis evaluation and treatment selection plan for ICC patients.
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Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.
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Objective:To explore the relationship between affective temperament and the severity of depressive symptoms in medical college students.Methods:From October to November 2021, a questionnaire survey was conducted among 1 780 medical undergraduates from two medical colleges in Anhui Province.The Chinese version of temperament scale of Memphis, Pisa, Paris and San Diego autoquestionnaire (TEMPS-A) and the Chinese version of the Beck depression inventory (BDI-Ⅱ) were used to evaluate the affective temperament and depressive symptoms of medical college students, respectively.SPSS 23.0 software was used for statistical analysis of the data.Ordinal Logistic regression model was used to analyze the impact of affective temperament characteristics on the severity of depressive symptoms.Results:The detection of depressive symptoms among medical college students was 6.4% with mild depression, 7.4% with moderate and severe depression and 86.2% without depression.The scores of cyclothymic, depressive, irritable, hyperthymia and anxious temperaments in TEMPS-A were significantly different among medical college students with different levels of depressive symptoms (all P<0.05). There were statistically significant differences in the detection rates of depression symptoms among medical college students with different typical affective temperament characteristics(all P<0.05). Ordinal Logistic regression model analysis showed that typical cyclothymic temperament ( OR=5.05, 95% CI: 3.68-6.94), typical depressive temperament ( OR=7.69, 95% CI: 4.64-12.86), typical hyperthymia temperament ( OR=0.30, 95% CI: 0.15-0.58), and typical anxious temperament ( OR=2.41, 95% CI: 1.75-3.32) were influencing factors for the severity of depressive symptoms in medical college students. Conclusion:Affective temperament, especially typical depressive temperament, typical cyclothymic temperament and typical anxious temperament can affect the severity of depressive symptoms in medical college students.
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Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.
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Objective:To explore the status of coronavirus disease 2019 (COVID-19) vaccines, safety and the influencing factors of adverse reactions in maintenance hemodialysis (MHD) patients.Methods:The study was a retrospective study. The MHD patients vaccinated with COVID-19 vaccines in Tianjin city from January 2020 to July 2022 were enrolled in the study. The data of general information, vaccination situation, adverse reactions, and laboratory tests before and after vaccination were collected. Logistic regression analysis was used to analyze the risk factors of adverse reactions after vaccination.Results:A total of 7 375 patients were registered to receive hemodialysis treatment in Tianjin city, of whom 1 036 patients (14.05%) vaccinated with COVID-19 vaccines were enrolled from 53 hemodialysis centers in the study, with age of (54.00±13.27) years old (17-88 years old), and 676 males (65.25%). There were 171 patients (16.51%) receiving the first dose of vaccines only, 464 patients (44.79%) receiving two doses of vaccines, 401 patients (38.71%) receiving three doses of vaccines, and 67 patients (6.47%) had adverse reactions. No serious adverse reaction occurred. The number of neutrophils after vaccination was lower than that before vaccination ( P < 0.05), while the number of lymphocytes, alanine aminotransferase, glutamic oxaloacetic aminotransferase, and serum albumin after vaccination were higher than those before vaccination (all P < 0.05). Logistic regression analysis showed that age ( OR=0.967, 95% CI 0.946-0.990, P=0.005), previous allergic history ( OR=0.013, 95% CI 0.001-0.151, P < 0.001), serum uric acid ( OR=1.004, 95% CI 1.001-1.008, P=0.020), numbers of vaccinations administered ( OR=0.505, 95% CI 0.330-0.774, P=0.002), leukocytes ( OR=0.766, 95% CI 0.628-0.935, P=0.009) and lymphocytes ( OR=0.082, 95% CI 0.045-0.148, P < 0.001) were independently correlated with the incidence of adverse reactions. Conclusions:The proportion of MHD patients vaccinated with COVID-19 vaccines is 14.05%. The incidence of adverse reactions is 6.47%, and there is no serious adverse reaction. Age, previous allergic history, serum uric acid, and numbers of vaccinations administered, leukocytes and lymphocytes are independently correlated with the incidence of adverse reactions in MHD patients.
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Objective:To analyze the expression of mucin 1 (MUC1) and Ki67 in intrahepatic cholangiocarcinoma (ICC), and to explore the correlations between the expression of MUC1 and Ki67 and the clinicopathological features and prognosis of ICC patients.Methods:Clinical data of 398 patients with ICC admitted to Henan Provincial People's Hospital from January 2013 to March 2020 were retrospectively analyzed. A total of 104 patients were included in this study, including 67 males and 37 females, aged (56.6±9.3) years. Immunohistochemistry was used to detect the expression of MUC1 and Ki67 in cancer tissues. Univariate and multivariate Cox regression analysis were used to study the prognostic factors of ICC patients.Results:The expression of MUC1 was low in 65 patients and high in 39 patients. Ki67 expression was low in 52 patients and high in 52 patients. High expression of MUC1 was correlated with lymph node metastasis ( P<0.05), while high expression of Ki67 was correlated with tumor nodes number, lymph node metastasis and vascular invasion (all P<0.05). Multivariate analysis showed that ICC patients with high MUC1 expression ( HR=2.321, 95% CI: 1.420-3.792, P<0.001) and high Ki67 expression ( HR=2.012, 95% CI: 1.247-3.247, P=0.004) showed a poor prognosis after hepatectomy. ICC patients with high MUC1 expression ( HR=1.664, 95% CI: 1.058-2.618, P=0.028) and high Ki67 expression ( HR=1.883, 95% CI: 1.168-3.035, P=0.009) had a poor prognosis after hepatectomy. Conclusion:High expression of MUC1 and Ki67 is correlated with tumor growth and metastasis. MUC1 and Ki67 are independent risk factors for prognosis of ICC patients after hepatectomy.
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Objective:To investigate the application value of peripheral blood circulating tumor cell (CTC) classification in the prediction of preoperative microvascular invasion of hepato-cellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinico-pathological data of 102 HCC patients who were admitted to Zhengzhou University People's Hospital from September 2018 to September 2020 were collected. There were 71 males and 31 females, aged from 29 to 80 years, with a median age of 57 years. Observation indicators: (1) surgical situations; (2) results of CTC detection and microvascular invasion in HCC patients; (3) results of CTC classification and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC; (4) influencing factors for microvascular invasion in HCC; (5) comparison of clinicopathological features in HCC patients with different cell counts in mesenchymal phenotype of CTC (M-CTC). Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the nonparametric rank sum U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. The receiver operating characteristic (ROC) curve was used to determine the best cut-off value for the risk of microvascular invasion in patients. Univariate and multivariate analysis were performed using the Logistic regression model. Results:(1) Surgical situations. All 102 patients underwent surgery successfully, including 17 cases undergoing local hepatectomy, 43 cases under-going segmentectomy, 22 cases undergoing hepatic lobectomy, 13 cases undergoing hemilectomy and 7 cases undergoing enlarged hemilectomy. The operation time and the volume of intraoperative blood loss were 235(147,293)minutes and 300(110,500)mL of the 102 patients, respectively. (2) Results of CTC detection and microvascular invasion in HCC patients. Of 102 patients, there were 36 casas with epithelial phenotype of CTC (E-CTC), 86 cases with hybrid phenotype of CTC (H-CTC), 30 cases with M-CTC, respectively, and the total CTC (T-CTC) were positive in 89 cases. Results of postoperative pathological examination showed that there were 40 cases with micro-vascular inva-sion and 62 cases without microvascular invasion in the 102 patients. Of the 40 patients with micro-vascular invasion, the count of E-CTC, H-CTC, M-CTC and T-CTC were 0(0,1) per 5 mL, 4(2,5) per 5 mL, 1(0,2) per 5 mL and 5(3,8) per 5mL, respectively. The above indicators of the 62 cases without microvascular invasion were 0(0,1) per 5 mL, 3(1,5) per 5 mL, 0(0,0) per 5 mL and 3(2,6) per 5 mL, respectively. There were significant differences in the count of M-CTC and T-CTC between patients with and without microvascular invasion ( Z=-4.83, -2.96, P<0.05). (3) Results of CTC classi-fication and the best cut-off value of CTC classification in the prediction of microvascular invasion in HCC. The ROC curve showed that best cut-off value of M-CTC and T-CTC counts in the prediction of microvascular invasion in HCC were 1 per 5 mL and 4 per 5 mL, respectively, with the area under curve, the corresponding specificity, sensitivity were 0.70 (95% confidence interval as 0.60-0.81, P<0.05), 75.8%, 62.9% and 0.67 (95% confidence interval as 0.57-0.78, P<0.05), 60.0%, 72.5%, respec-tively. (4) Influencing factors for microvascular invasion in HCC. Result of univariate analysis showed that alpha fetoprotein (AFP), aspartate aminotransferase (AST), tumor diameter, tumor number, tumor margin, Barcelona clinic liver cancer staging, M-CTC counts and T-CTC counts were related factors influencing microvascular invasion in HCC ( odds ratio=3.13, 0.43, 4.92, 5.65, 2.54, 2.93, 8.25, 4.47, 95% confidence interval as 1.34-7.33, 0.19-0.98, 2.09-11.58, 2.35-13.63, 1.13-5.75, 1.27-6.74, 3.13-21.75, 1.88-10.61, P<0.05). Result of multivariate analysis showed that tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL were independent risk factors influencing microvascular invasion in HCC ( odds ratio=2.97, 4.14, 4.36, 95% c onfidence interval as 1.01-8.70, 1.14-15.02, 1.36-13.97, P<0.05). (5) Comparison of clinicopathological features in HCC patients with different cell counts in M-CTC. The 102 HCC patients were divided into the high M-CTC group of 30 cases with M-CTC counts ≥1 per 5 mL and the low M-CTC group of 72 cases with M-CTC counts <1 per 5 mL, according to the best cut-off value of M-CTC counts. Cases with hepatitis, cases with AFP >400 μg/L, cases with AST >35 U/L, cases with irregular tumor margin, cases with tumor diameter >5 cm, cases with tumor number as multiple and cases with micro-vascular invasion were 22, 17, 13, 21, 18, 16 and 22 in the high M-CTC group of 30 cases. The above indicators were 35, 18, 48, 26, 25, 21 and 18 in the low M-CTC group of 72 cases. There were significant differences in the above indicators between the high M-CTC group and the low M-CTC group ( χ2=5.25, 9.42, 4.80, 9.79, 5.55, 5.35, 20.75, P<0.05). Conclusions:The epithelial-mesen-chymal phenotype of peripheral blood CTC can be used to predict the preoperative microvascular invasion in HCC. Tumor diameter >5 cm, tumor number as multiple and M-CTC counts ≥1 per 5 mL are independent risk factors influencing microvascular invasion in HCC patients.
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Objective:To determine the risk factors for development of combined hepatocellular-cholangiocarcinoma (CHC) and intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with ICC or CHC confirmed by pathology at Henan Provincial People's Hospital from January 2012 to December 2018 were retrospectively analyzed. Of 225 patients with ICC or CHC, there were 90 males and 135 females, aged (58.7±10.4) years old. Based on the pathological type, there were 172 patients in the ICC group and 53 patients in the CHC group. The healthy control group was selected from 450 individuals who underwent routine health examination in the same hospital, and there were 189 males and 261 females, aged (56.7±9.3) years old. Univariate and multivariate logistic regression were used to analyze the risk factors of ICC and CHC.Results:The risk factors of ICC included hepatitis B surface antigen (HBsAg) (+ )/hepatitis B core antibody (anti-HBc) (+ ) ( OR=9.373, 95% CI: 4.784-18.363, P<0.001), hepatitis C virus antibody (HCV-Ab) (+ ) ( OR=7.151, 95% CI: 1.195-42.776, P=0.031), diabetes mellitus ( OR=3.118, 95% CI: 1.733-5.612, P<0.001) and hepatolithiasis ( OR=18.650, 95% CI: 5.210-66.767, P<0.001). The risk factors of CHC included HBsAg (+ )/anti-HBc(+ )( OR=54.891, 95% CI: 17.434-172.822, P<0.001) and HCV-Ab (+ ) ( OR=37.785, 95% CI: 5.720-249.611, P<0.001). Conclusion:HBV infection, HCV infection, hepatolithiasis, diabetes mellitus and cirrhosis were risk factors for ICC. HBV and HCV infection were risk factors of CHC.
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Plasma cell disorders are a group of heterogeneous diseases originating from plasma cells, including multiple myeloma, plasma cell leukemia and light-chain amyloidosis, etc. Monoclonal plasma cells are detected in bone marrow and affected tissues, monoclonal immunoglobulin or components are detected in serum or urine, and some end-organs are injured. Plasma cell disorders accompanied by t(11;14) have unique biological characteristics and unsatisfactory response to proteasome inhibitors. With t(11;14) translocation, the expressions of cyclin D1 and anti-apoptotic protein bcl-2 are relatively high, which lead to the occurrence of plasma cell disorders and have implications for the prognosis of disease. Venetoclax is a bcl-2 inhibitor, and its single agent or combined with other drugs has achieved good efficacy in treatment of plasma cell disorders with t(11;14). This article reviews the progress of bcl-2 inhibitors in treatment of plasma cell disorders.
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Objective:To investigate the application value of fusion indocyanine green fluorescence imagine (FIGFI) in laparoscopic common bile duct reexploration.Methods:The clinical data of 65 patients who underwent laparoscopic common bile duct reexploration at Henan Province People′s Hospital from Jan 2015 to Dec 2019 were collected. According to the operational manner, the patients were divided into the conventional laparoscopic group (control group, 35 patients) and the FIGFI laparoscopic group (study group, 30 patients). The intraoperative and postoperative data were analyzed.Results:Operation time, time to identify extrahepatic bile duct, intra operative blood loss, and conversion to open surgery were (195.7±9.2) min vs (147.2±9.3) min, (39.3±3.7) min vs (21.8±1.8) min, (203.2±34.6) ml vs (108.9±32.1) ml, 8 vs 1, between the control group and the study group, respectively ( P<0.05). Postoperative cholangitis, bile leakage, intra abdominal infection, pancreatitis, and hospital stay were 11vs 2, 9 vs 2, 8 vs 1, 8 vs 1, (13.5±0.9) d vs (7.4±0.9) d, between the control group and the study group, respectively ( P<0.05). There was no statistically difference in case of residual stones (5 vs 3) and gastrointestinal fistula (3 vs 1) between the control group and the study group, respectively ( P>0.05). Conclusions:FIGFI provides real-time visualization of the extrahepatic biliary tract while doing laparoscopic common bile duct reexploration.
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Objective:To investigate the predictive value of portal vein (PoV) blood circulating tumor cells (CTCs) count in patients with pancreatic cancer on the postoperative prognosis.Methods:The data of 58 patients receiving radical resection of pancreatic cancer and PoV CTCs detection at People's Hospital of Zhengzhou University from Aug 2018 to Jun 2020 were collected. According to the cut-off value of PoV CTCs>10/5 ml made by receiver operating characteristic curve (ROC), patients were divided into high CTCs group and low CTCs group and the differences in clinicopathological parameters and prognosis of the two groups were compared.Results:Postoperative progression-free survival rate of the low CTCs group was higher than that of the high CTCs group ( χ 2=12.97, P<0.001).Univariate COX regression analysis showed that tumor diameter >4 cm, lymph node invasion, TNM staging, CTCs>10/5 ml, postoperative CA199>37 U/m were risk factors for postoperative prognosis. Multivariate COX regression analysis demonstrated that TNM stage ( OR=2.782, P=0.024), CTCs count >10/5 ml ( OR=2.583, P=0.047), postoperative CA199>37 U/m ( OR=3.775, P=0.004) were the independent risk factors of prognosis. Conclusion:A higher PoV CTCs count was a risk factor for poor prognosis of patients with pancreatic cancer after radical resection.
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2,5-dimethylpyrazine (2,5-DMP) is of important economic value in food industry and pharmaceutical industry, and is now commonly produced by chemical synthesis. In this study, a recombinant Escherichia coli high-efficiently converting L-threonine to 2,5-DMP was constructed by combination of metabolic engineering and cofactor engineering. To do this, the effect of different threonine dehydrogenase (TDH) on 2,5-DMP production was investigated, and the results indicate that overexpression of EcTDH in E. coli BL21(DE3) was beneficial to construct a 2,5-DMP producer with highest 2,5-DMP production. The recombinant strain E. coli pRSFDuet-tdh(Ec) produced (438.3±23.7) mg/L of 2,5-DMP. Furthermore, the expression mode of NADH oxidase (NoxE) from Lactococcus cremoris was optimized, and fusion expression of EcTDH and LcNoxE led to balance the intracellular NADH/NAD⁺ level and to maintain the high survival rate of cells, thus further increasing 2,5-DMP production. Finally, the accumulation of by-products was significantly decreased because of disruption of shunt metabolic pathway, thereby increasing 2,5-DMP production and the conversion ratio of L-threonine. Combination of these genetic modifications resulted in an engineered E. coli Δkbl ΔtynA ΔtdcB ΔilvA pRSFDuet-tdhEcnoxELc-PsstT (EcΔkΔAΔBΔA/TDH(Ec)NoxE(Lc)-PSstT) capable of producing (1 095.7±81.3) mg/L 2,5-DMP with conversion ratio of L-threonine of 76% and a yield of 2,5-DMP of 28.8% in 50 mL transformation system with 5 g/L L-threonine at 37 °C and 200 r/min for 24 h. Therefore, this study provides a recombinant E. coli with high-efficiently catalyzing L-threonine to biosynthesize 2,5-DMP, which can be potentially used in biosynthesis of 2,5-DMP in industry.
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Escherichia coli/genetics , Lactococcus , Metabolic Engineering , Pyrazines , ThreonineABSTRACT
Objective:To analyze the clinicopathological features, diagnosis and treatment of neuroendocrine carcinoma of gallbladder (GB-NEC).Methods:The clinical data of 17 patients with GB-NEC confirmed by postoperative pathology managed at the People's Hospital of Zhengzhou University from March 2013 to January 2020 were analyzed retrospectively. There were 9 males and 8 females, with an age of (68.9±11.2) years. The clinical and follow-up data were analyzed.Results:The main clinical manifestations were abdominal pain ( n=9, 52.9%), anorexia ( n=5, 29.4%), jaundice ( n=2, 11.8%), abdominal mass ( n=2, 11.8%), and asymptomatic ( n=2, 11.8%). Radical resection of gallbladder carcinoma was performed in 9 patients, and palliative resection in 8 patients. Postoperative chemotherapy was given to 4 patients. Postoperative pathology showed small cell type in 11 patients and large cell type in 6 patients. Immunohistochemical staining showed synaptophysin positivity in 17 patients (100.0%), chromogranin A positivity in 12 (70.6%), Ki67 positivity in 17 patients (100%, >50% was defined as positive). All 17 patients were followed-up from 78 to 745 days, with a median of 237 days. At the time of censor of this study, 13 patients had died. The 1-and 2-year cumulative survival rates were 26.5% and 19.9%, respectively. The 1- and 2-year cumulative survival rates of radical gallbladder carcinoma resection ( n=9) were 44.4% and 33.3%, respectively. Eight patients underwent palliative resection, and the longest follow-up time was 276 days. Conclusion:This study showed the incidence of GB-NEC was low. There was no specific clinical manifestations, and the diagnosis mainly depended on immunohistochemistry. Patients with GB-NEC had high expressions of Ki67 and had poor prognosis. Early radical resection was helpful to improve survival of these patients.
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Objective:This study aimed to compare the clinical outcomes of laparoscopic pancreaticoduodenectomy (LPD) versus open pancreaticoduodenectomy (OPD).Methods:The clinical data of 386 patients who successfully underwent pancreaticoduodenectomy at the People's Hospital of Zhengzhou University from June 2017 to December 2019 were retrospectively analyzed. According to the different surgical methods, patients were divided into the LPD group ( n=122) and the OPD group ( n=264). The differences in operation time, intraoperative blood loss, postoperative hospital stay, postoperative complications, postoperative oncology survival outcomes and prognosis between groups were compared. Results:Of 386 patients in this study, there were 232 males and 154 females, aged (57.8±11.0) years. The operation time of the LPD group was (330.69±80.55) min which was significantly longer than that of the OPD group (241.13±77.24) min. The intraoperative blood loss 300.00(200.00, 400.00) ml was also significantly less than the OPD group 400.00(262.50, 500.00) ml, and the length of postoperative stay in the LPD group (12.21±5.24) d was significantly less than the OPD group (16.61±6.63) d, (all P<0.05). There were 36 patients (29.51%) in the LPD group and 81 patients (30.68%) in the OPD group who developed postoperative complications, with no significant difference between groups ( P>0.05). Postoperative oncology outcomes showed that the number of lymph nodes dissected in the LPD group was significantly more than that in the OPD group [(12.65±5.03) vs (10.07±5.09)], ( P<0.05). There were no significant differences between the two groups in tumor pathology type, size, degree of differentiation and R 0 resection rates (all P>0.05). All patients were followed up for 6-36 months, with a median follow-up of 20 months. The survival rates of patients with malignant tumors after following-up for more than 1 year in the LPD group was 84.72%(61/72), that in the OPD group was 85.81%(133/155), with no significant difference between groups ( P>0.05). Conclusion:LPD was safe and feasible with its advantages of minimally invasiveness.
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Seven indole alkaloid glycosides containing a 1'-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (-) were isolated from an aqueous extract of leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of -, two simple roles to assign location and/or configuration of -glycopyranosyloxy and 1'-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of - is discussed. Compounds and and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of and (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC 64.7 μmol/L (ribavirin, IC 54.3 μmol/L), however, the individual or was inactive. Preliminary structure-activity relationships were observed.
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Objective:To investigate the effects of abdominal aortic calcification (AAC) progression on outcomes in maintenance hemodialysis (MHD) patients.Methods:Patients who were on MHD between Jun. 2014 and Oct. 2014 in the dialysis center of the Second Hospital of Tianjin Medical University and finished the AAC examination at baseline and two years later were included prospectively. The progression of AAC by AAC score (AACs) at baseline and two years later was evaluated. According to the change of AACs, the patients were divided into rapid AAC progression group and non-rapid AAC progression group. The effect of AAC progression on outcomes in MHD patients in the follow-up period was investigated. Kaplan-Meier analysis was used to compare their survival rates. Multivariable Cox regression model was used to determine the risk factors of all-cause mortality, cardiovascular mortality and cardiovascular events.Results:A total of 111 MHD patients were included, including 51 males and 60 females, aged (52.24±12.69) years. Baseline AAC prevalence was 45.9% (51/111), and median AACs was 0 (0, 5); After 2 years, the prevalence of AAC was 78.4% (87/111), and the median AACs was 6 (2, 11). There were 54 cases in the AAC rapid progression group (AACs change value>2) and 57 cases in the non-rapid AAC progression group (AACs change value≤2). The median follow-up duration was 27.9(27.1, 28.0) months. Kaplan-Meier analysis showed that patients in rapid AAC progression group had a higher risk of mortality as compared to patients in non-rapid AAC progression group (Log-rank χ2=5.695, P=0.017). Multivariate Cox regression analysis demonstrated that high baseline AACs ( HR=1.135, 95% CI 1.001-1.286, P=0.048), hypoalbuminemia ( HR=0.789, 95% CI 0.640-0.972, P=0.026) were independent risk factors for all-cause mortality in MHD patients. High baseline AACs ( HR=1.187, 95% CI 1.038-1.356, P=0.012), low spKt/V ( HR=0.103, 95% CI 0.013-0.801, P=0.030) were independent risk factors for cardiovascular mortality in MHD patients. Low spKt/V ( HR=0.018, 95% CI 0.003-0.115, P<0.001), hypoalbuminemia ( HR=0.736, 95% CI 0.608-0.890, P=0.002) were independent risk factors for cardiovascular events in MHD patients. Conclusions:Abdominal aortic calcification progression may increase the risk of cardiovascular events and death in MHD patients. Severity of AAC, adequacy of dialysis, and nutritional status are predictors of outcomes in MHD patients.
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Objective:To investigate the induction mechanism of cisplatin on hepatoma senescence.Methods:2 μg/ml cisplatin was applied to affect hepatocellular carcinoma cell line HepG2. Cell proliferation of tumor cells was detected by MTS method. The cell cycle was detected by flow cytometry. The RT-PCR and Western blot were used to detect the expression of senescence regulation genes, p19 and p21. The expression of p21 was detected by cell immunofluorescence. Nude mouse model of human hepatocellular carcinoma was intraperitoneally injected with specific drug to measure the growth, metastasis of tomor and expression of p21 protein.Results:Cell proliferation rate in cisplatin group was lower than that of the control group( t=8.958, P<0.05). Flow cytometry showed the percentage of G 2 phase were19.90%±0.42%, 12.57%±0.84% in the cisplatin and control group, respectively. Cells were arrested in G 2 phase ( t=14.415, P<0.05). In the cisplatin group and control group, the relative expression of p19 were(2.23±0.05), (1.00±0.02); the relative expression of p21 were (3.26±0.11), (1.00±0.02). The expression of p19 and p21 increased(respectively t=43.750, 56.541, all P<0.05). The tumor size of cisplatin group was smaller than that of the control group, and the expression level of p21 protein was higher than that of the control group ( P<0.05). Conclusion:Cisplatin can induce senescence of hepatocellular carcinoma cells through the p19/p21 pathway.
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Objective To investigate the clinical effect of three-dimensional laparoscopic splenectomy for massive splenomegaly secondary to liver cirrhosis.Methods The clinical data of 67 patients who underwent laparoscopic splenectomy for massive splenomegaly at Henan Province People's Hospital from Jan 2013 to Dec 2018 were collected.Results Operation time,volume of intraoperative blood loss and blood transfusion,number of patients with intraoperative blood transfusion,and conversion to laparotomy were in favor of 3D group,with statistically differences (t =12.900,18.255,19.711,x2 =10.747,0.685,P ＜ 0.05).Postoperative intraabdominal bleeding,pancreatic fistula,and postoperative hospital stay in 2D group were more than those in 3D group,with statistically differences (x2 =3.511,4.527,t =12.969,P ＜ 0.05).All patients were followed up for 5 to 60 months.Portal thrombosis occurred in 6 patients vs 5 patients,respectively (x2 =0.028,P ＞ 0.05) and resolved with oral coumarin.Conclusions Three-dimensional laparoscopic splenectomy can provide more realistic visual effects of surgical procedures and has an obvious advantage in laparoscopic splenectomy for massive splenomegaly secondary to liver cirrhosis.
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Objective To study the effects of different parenteral nutrition on acute inflammatory response,immune cells and lipid metabolism in patients after pancreaticoduodenectomy.Methods Eighty patients after pancreaticoduodenectomy were divided into study group and control group,with 40 cases in each group.Structural fat emulsion was used in study group and medium/long chain fat emulsion in control group.The changes of acute inflammation,immune cells and lipid metabolism were compared between the two groups.Results (1)The levels of C-reactive protein (CRP) and serum prostaglandin E2 (PGE2) in the two groups were significantly higher on the first day after operation than those before operation.The difference between the two groups was statistically significant (P ＜ 0.05).The level of CRP and PGE2 decreased to the preoperative level on the seventh day after operation,but the decline rate in the study group was significantly faster than that in the control group (P ＜ 0.05).(2) The levels of CD3 +,CD4 +,CD8 +,CD4 +/CD8 + in the study group were significantly higher than those in the control group (P ＜ 0.05).(3) After 3-7 days of intravenous parenteral nutrition infusion,the blood lipid level was significantly lower in study group (P ＜ 0.05).Conclusion Structural fat emulsion alleviates the inflammatory reaction in patients after pancreaticoduodenectomy,promotes the recovery of immunity,significantly reduces the level of blood lipids.