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Objective:To investigate the relationship between KRAS gene mutation, programmed death receptor ligand 1 (PD-L1) expression and prognosis of first-line concurrent chemoradiotherapy in patients with locally advanced non-small cell lung cancer.Methods:The clinical data of 50 patients with locally advanced non-small cell lung cancer who were admitted to Nanping First Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients were treated with first-line concurrent chemoradiotherapy. Tissue samples of patients were obtained and paraffin embedded before treatment. Real-time fluorescence quantitative polymerase chain reaction was used to detect the type of KRAS gene mutation in tissues before treatment, and the expression of PD-L1 was determined by immunohistochemistry (the percentage of positive cells in tumor cells ≥1% was positive), and the relationship between KRAS gene status, PD-L1 expression and clinical characteristics and short-term efficacy of patients was analyzed. Patients were followed up for 1 year, and progression-free survival (PFS) curves were plotted by Kaplan-Meier method, and log-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to analyze the influencing factors of PFS.Results:Among the 50 patients, 11 (22.00%) were KRAS mutant, and 36 (72.00%) were PD-L1 positive. Among the 11 patients with KRAS mutation, there were 2 cases of codon 13 mutation and 9 cases of codon 12 mutation in exon 2. The objective response rate (ORR) and clinical control rate (DCR) were 76.00% (38/50) and 86.00% (43/50). There were no significant differences in patients' age, pathological type, TNM stage, ORR and DCR between KRAS mutant group and KRAS wild type group (all P > 0.05). The proportions of male patients [72.73% (8/11) vs. 38.46% (15/39)], patients with smoking history [90.91% (10/11) vs. 20.51% (8/39)] and patients with PD-L1 positive expression [100.00% (11/11) vs. 64.10% (25/39)] in KRAS mutant group were higher than those in KRAS wild type group (all P < 0.05). There were no significant differences in patients' age, pathological type, gender, smoking history, TNM stage, ORR and DCR between PD-L1 positive group and PD-L1 negative group (all P > 0.05). The median PFS time of patients in KRAS mutant group and wild type group was 8.75 and 11.32 months, and the difference in PFS between the two groups was statistically significant ( P = 0.039). The median PFS time of patients with PD-L1 positive and negative was 10.19 and 11.16 months, and there was no statistical significance in PFS between the two ( P = 0.116). Multivariate Cox regression analysis showed that KRAS gene mutation was an independent risk factor for PFS in patients with locally advanced NSCLC after first-line concurrent chemoradiotherapy ( HR = 1.449, 95% CI 1.071-1.196, P = 0.017). PD-L1 expression, smoking history and gender were not independent influencing factors for PFS (all P > 0.05). Conclusions:KRAS gene status is closely related to the prognosis of patients with locally advanced non-small cell lung cancer treated with first-line concurrent chemoradiotherapy, while PD-L1 expression is not.
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Objective To evaluate the effect of the different Child-Pugh classification on the recurrence and survival of hepatocellular carcinoma (HCC) recipients after liver transplantation. Methods Clinical data of 125 HCC recipients undergoing liver transplantation were retrospectively analyzed. The 3-year disease-free survival (DFS) and overall survival (OS) rates were calculated by Kaplan-Meier survival curve. The independent risk factors probably affecting the recurrence and survival of HCC recipients after liver transplantation were identified by using Cox's proportional hazards regression model. Results The median follow-up time was 25.6 months. The 3-year DFS and OS rates were 68.4% and 65.7% for all patients. The 3-year DFS and OS rates in 113 patients with Child-Pugh class A/B HCC were 68.6% and 66.2%, whereas 66.7% and 65.6% for 12 patients with Child-Pugh class C HCC with no statistical significance (all P>0.05). Cox's proportional hazards regression model demonstrated that vascular invasion (P=0.001)and the number of tumors>3 (P=0.025) were the independent risk factors for the postoperative recurrence of HCC in recipients undergoing liver transplantation. Alpha fetoprotein (AFP)>400μg/L (P=0.035), vascular invasion (P=0.031) and number of tumors>3 (P=0.008) were the independent risk factors affecting the survival of HCC patients. Conclusions The postoperative prognosis does not significantly differ between Child-Pugh class C and A/B HCC patients after liver transplantation. AFP, vascular invasion and number of tumors are the risk factors affecting the clinical prognosis of HCC patients after liver transplantation. Liver transplantation is an efficacious treatment for HCC patients with Child-Pugh class C.
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Objective To establish a non-venous bypass orthotopic liver transplantation model in Bama miniature pigs with high repeatability and stability. Methods Twelve Bama miniature pigs were randomly divided into the donor group (n=6) and recipient group (n=6). Pigs underwent non-venous bypass orthotopic liver transplantation. The time of anhepatic phase during operation was shortened, blood pressure during anhepatic phase was stably maintained, and management of anesthesia and body fluid during operation were strengthened. The operation time, anhepatic phase and survival status of the recipients were observed and recorded. The intraoperative heart rate, mean arterial pressure (MAP) and changes in arterial blood gas analysis were monitored. The perioperative liver function was evaluated. Results Among 6 Bama miniature pigs, 1 died from transplantation failure intraoperatively. The operation time of the remaining 5 pigs was (247±27) min and the time of anhepatic phase was (46±4) min. Three animals survived for more than 2 weeks. Compared with the preanhepatic phase, the heart rate of the animals was significantly faster, MAP was considerably reduced to (46±6) mmHg, blood pH value, base excess (BE) and HCO3- level were all significantly decreased and serum level of K+ was significantly elevated during the anhepatic phase (all P < 0.05). In the neohepatic phase, MAP of Bama miniature pigs was significantly increased, heart rate was dramatically slower.Blood pH value, BE, HCO3- level were significantly increased and serum level of K+ was significantly declined (all P < 0.05). During abdominal closure, MAP, blood gas indexes and serum level of K+ were almost recovered to those in the preanhepatic phase. Compared with preoperative levels, the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH)and alkaline phosphatase(ALP)were significantly increased after operation (all P < 0.05), the change in AST was the most obvious, and it gradually decreased at postoperative 2 d. The level of γ-gutamyl transferase(GGT) did not significantly elevated. The level of total bilirubin (TB) was evidently elevated at postoperative 5 d. Compared with the preoperative levels, the levels of total protein (TP) and albumin (ALB) were significantly decreased after operation (both P < 0.05), and began to gradually increase at postoperative 1 d. Conclusions The non-venous bypass orthotopic liver transplantation model of Bama miniature pig is convenient, with highly reproducible and survival rate, which can be utilized as a standardized liver transplantation model.
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Objective To investigate the effect of nuclear factor erythroid-2-related factor 2(Nrf2) on the anti-hypoxia and anti-apoptotic ability of mesenchymal stem cells(MSCs). Methods Human embryonic kidney cells(293FT) were transfected with recombinant plasmid which overexpressed Nrf2 and helper plasmid. High-titer lentivirus which overexpressed Nrf2 were obtained. MSCs were transfected with lentivirus with Nrf2 overexpression and empty lentiviral vector to establish Nrf2-MSCs which stably overexpressed Nrf2 (Nrf2 overexpression group) and green fluorescent protein (GFP)-MSCs(control group). The expression of green fluorescent in 2 groups was observed by fluorescence microscope. The expression level of Nrf2 protein in 2 groups was measured by Western Blot. The anti-hypoxia ability of 2 groups was observed by light microscope. The anti-apoptotic ability of 2 groups was measured by flow cytometry. Results Nrf2-MSCs which stably overexpressed Nrf2 were successfully established. Western Blot analysis revealed that the expression level of Nrf2 protein in the Nrf2 overexpression group was significantly higher than that in the control group(P<0.01). After 15 h hypoxia treatment, the cell activity in the Nrf2 overexpression group was significantly higher than that in the control group. Flow cytometry showed that the apoptosis rate in the Nrf2 overexpression group was (30.9±1.4)%, significantly lower than (61.3±1.3)% in the control group(P<0.05). Conclusions Nrf2-MSCs which can stably overexpress Nrf2 possess certain anti-hypoxia and anti-apoptotic ability in hypoxia environment.
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Objective To evaluate the clinical efficacy of application of hepatitis B surface antigen (HBsAg)-positive donor liver in adult liver transplantation. Methods Clinical efficacy of 28 recipients with liver diseases induced by virus B hepatitis (hepatitis B) undergoing liver transplantation using HBsAg-positive donor liver from July 2012 to October 2015 was retrospectively analyzed. Clinical prognosis and postoperative complications of the recipients were summarized. The changing features of serum levels of HBsAg and hepatitis B virus (HBV) DNA was investigated. Results After liver transplantation, 28 recipients were orally administered with entecavir to prevent the recurrence of hepatitis B. During perioperative period, 2 recipients died from sepsis and acute heart failure. During postoperative follow-up, 2 cases died from the recurrence of hepatocellular carcinoma (liver cancer). The remaining 24 patients were followed up for 12-26 months. Throughout the follow-up, 24 recipients were positive for serum HBsAg. After treatment, the titre of HBV DNA was significantly declined to <1×102 copies/mL at postoperative 12 months. No graft dysfunction induced by hepatitis B recurrence occurred in 24 recipients alive. Conclusions As a marginal donor liver, HBsAg-positive liver graft is safe for liver transplantation in the recipients with hepatitis B-related liver diseases. Postoperatively, anti-HBV treatment should be strengthened and intimate follow-up should be delivered.
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Objective To analyze the effection of improved three-dimensional conformal radiotherapy (3D-CRT) to the dose of target area of local advanced non-small-cell lung cancer (NSCLC) and observe the therapeutic efficacy and toxity.Methods 81 patients with local advanced NSCLC were collected and treated.The diameter of tumor exceed 5 cm.52 patients were squamous carcinoma.24 patients were adencarcinoma.5 patients were adenosquamous carcinoma.63 patients were onstage of Ⅲ A,18 patients were Ⅲ B.The patients were randomized into two groups,the first group was unmodified planning of 3D-CRT group (T1 group,39 patients),the second group was modified planning of 3D-CRT group (T2 group,42 patients).The 31 patients of T1 group (79.5 ％) received radiotherapy and chemotherapy.Toties quoties was 2 Gy.The fractions were 26-30.The total dose was 52-60 Gy.The 31 patients of T1 group (73.8 ％) received radiotherapy and chemotherapy.Toties quoties was 2 Gy.The fractions were 30-35.The total dose was 60-70 Gy.Results The 1-,2-,3-year overall survive rates of T1 group were 56.4 ％,33.3 ％,28.4 ％,the 1-,2-,3-year local control survive rates were 38.4 ％,28.2 ％,20.5 ％,and the median survive time was 17 months.The 1-,2-,3-year overall survive rates of T2 group were 61.9 ％,35.7 ％,28.5 ％,the 1-,2-,3-year local control survive rates were 47.6 ％,40.4 ％,30.9 ％,and the median survive time was 19 months.The significant difference was found for the local control survive rates between T1 and T2 group (P ＜ 0.05).No significant difference was found for the overall survive rates and the median survive time between T1 and T2 group (P ＞ 0.05).Conclution Improved 3D-CRT can advance local control survive rate and living quality to local advanced NSCLC.Meanwhile,it also increases survive rate of 1-year,but can not increase long-time survival rate.
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OBJECTIVE@#To study MSCT perfusion imaging of nasopharyngeal cancer and its differentiated diagnosis.@*METHOD@#Thirty cases with nasopharyngeal cancer performed multi-detector CT perfusion examination. Among them, there were 6 cases of 25 post-radiotherapy patients performed perfusion imaging with CT scan. Nasopharynx perfusion parameters include blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS).@*RESULT@#Compared with normal region of nasopharynx, BF, BV and PS in nasopharyngeal cancer increased significantly, while MTT has not significant difference between these two areas.@*CONCLUSION@#Nasopharynx perfusion parameters (BF, BV and PS) measured with CT were significantly altered in nasopharyngeal cancer. There was important appliance value in differentiated diagnosis of nasopharyngeal malignant neoplasms and evaluation of outcome of radiotherapy of nasopharyngeal cancer.