Objective To compare the efficacy and safety of icotinib therapy alone versus icotinib combined with thoracic radiotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) patients with an activating epidermal growth factor receptor (EGFR) gene mutation.Methods A total of 83 patients with advanced NSCLC harboring an activating EGFR gene mutation was enrolled in this study.All the patients were randomly divided into 2 groups.Patients in group A (n =41) received thoracic radiotherapy (prescribed at 60-66 Gy) combined with icotinib (three times per day,125 mg once).Patients in group B (n =42) were given icotinib therapy alone (three times per day,125 mg once).Treatment was continued until disease progression or unacceptable toxicity or death.The primary end points were median progression-free survival (mPFS) and 12 month-PFS rate.The secondary end points included objective response rate (ORR),disease control rate (DCR) and adverse events.Results With a median follow-up of 18.2 months,mPFS was 15.2 months (95％ CI:12.2-17.4) in group A and 13.2 months (95％ CI:10.8-14.9) in group B (x2 =4.29,P=0.036).PFS rates of 12 months for group A and group B were 70.3％ and 61.2％,respectively.The ORR were 78.0％ vs.57.1％ (x2 =5.16,P =0.028),and the DCR were 95.1％ vs.92.9％ (P＞0.05) in groups A and group B,respectively.No grade 3-4 adverse events was observed in both groups except the rashes (4 cases in each group).Besides,10 patients had grade 1-2 radiation-related pneumonitis and 15 patients suffered grade 1-2 radiation-related oesophagitis in group A.Conclusions In advanced NSCLC patients with an activating EGFR gene mutation,the combination of thoracic radiotherapy and icotinib had achieved an improvement on ORR and PFS with good tolerance.Clinical trial registration Chinese clinical trial registry,ChiCTRINR-16010262.

[Objective] To observe NGF on cultured human retinal vascular endothelial cells (HRCEC) proliferation. [Methods] The MTT assay was used to analyze the impact of culture HRCEC on different factors (NGF concentration groups, NGF + K252a concentration groups, bFGF group, bFGF + K252a groups, the normal culture medium groups) in normal and hypoxic condition. [Results] With the increase of NGF concentration (20,50,100 ng/mL), HRCEC significantly increased (normal condition: 0.254±0.033,0.696±0.029, 1.136±0.051; hypoxic condition: 0.422±0.036, 0.798±0.044, 1.376±0.052, P< 0.05). Compared NGF + K252a group with the same concentration of NGF (100 ng/ml) group, HRCEC reduced (P<0.05), with increasing the concentration of K252a (50,100,200 nmol/L), the trend of HRCEC decreasing is become more significant (normal condition:0.864±0.067, 0.496±0.025, 0.202±0.078; hypoxic condition:K252a 1.042±0.047,0.700±0.065, 0.401±0.078, P<0.05). [Conclusion] NGF can promote the proliferation of HRCEC, the effect could be specifically blocked by TrkA inhibitor K252a.

Objective To observe the changes of cell cycle on cancer cells after dihydroartemisinin and X-ray irradiation. Methods Human HeLa cells of cervical cancer with p53 mutation was used and human SiHa cells of cervical cancer with wild p53 was used as control. Flow cytometry was used to detect the effect of dihydroartemisinin (20 and 100 μmol/L) and irradiation (6 Gy)on cell cycle. Western blot was used to measure the levels of cell cycle protein. Results G2 arrest was observed in irradiated HeLa cells, which the proportion of cells in G2 phase was increased from 14.45% to 73. 58% after 6 Gy X-ray irradiation, but it was abrogated by dihydroartemisinin from 73. 58% to 48.31%in HeLa cells, and it had no change on the SiHa cells. The elevated Weel protein and the lowered Cyclin B1 protein were observed with the G2 arrest severity. The expression of radiation-induced Weel protein was suppressed and the Cyclin B1 protein was increased after dihydroartemisinin treatment, which was in accordance with the abrogation of radiation-induced G2 delay. Conclusions The main effect of irradiation on cell cycle of p53 mutated HeLa cells is G2 arrest. Dihydroartemisinin could abrogate it, which is associated with the changes of Weel protein and Cyclin B1 protein. In Siha cells, the main effect of irradiation on cell cycle is G1 arrest, and dihydroartemisinin has no effect on it.

Objective To analyze the clinical and pathological features,diagnosis and differential diagnosis,treatment and prognosis of retroperitoneal angiomyolipoma (RAML).Methods The clinical data of 3 cases diagnosed with RAML,during 2012 to 2014 were studied.The expression of AE1/AE3,Vimentin,HMB45,Melan-A,S-100,SMA,CD10,CD34 and Ki-67 were detected by full automatic immunohistochemistry instrument.Four cases were followed up,the relevant published articles were reviewed as well.Results Four patients contained 3 female and 1 male.Three patients of them were found because of abdominal pain and discomfort symptom,1 case was found on examination.All of them more than 10 cm,and the boundary was not clear.Tumor resection + nephrectomy were used for treatment.Macroscopically,the tumor were consisted of fat,muscle cells and thick walled blood vessels.But they had different proportion.Immunohistochemically:AE1/AE3 negative; Vimentin,HMB45,Melan-A,SMA were positive; S-100 was positive in 3 cases and negative in 1 case; Ki-67 proliferation index were ＜5％.Conclusions The RAML is a rare benign retroperitoneal stromal tumor,which has a complex and diverse pathological organizations.The diagnosis can be made by special immune phenotype in combination with microscopic appearance.

Objective To study the radiosensitizing effect of caffic acid phenethyl ester(CAPE)on human cervical cancer HeLa cells.Methods MTT assay was used to measure the relation between the inhibition effect and CAPE concentrations by CAPE with different concentrations on HeLa cells for 24 hours.HeLa cells were divided into the control and experimental groups,both of which were given 0,2,4,6 and 8 Gy of 60Co γ-irradiation,respectively.The cell clones were counted.Meanwhile HeLa cells were divided into the control,CAPE,irradiation and combination groups.Flow cytometric analysis was adopted to detect the changes of cell cycle distribution induced by CAPE.Results The inhibition rate of CAPE acting on Hela cells increased with concentrations(F=126.49～3654.88,P＜0.01).HeLa cells cloning survival decreased with the increase of radiation dose(F=174.42～9422.81,P＜0.01).At the game radiation dose,HeLa cells cloning survival was less in experimental group than conlrol group(F=120.14～251.91,P＜0.01).The mean lethal dose(D0)(1.45 and 1.82 Gy)and the quasi-threshold dose(Dq)(1.89 and 3.21 Gy)of HeLa cells in experimental group decreased comparing with control group,SER was 1.26.Compared with the sole irradiation group,cells in G2/M phase of the CAPE group and the sole irradiation group increased(P＜0.01)while the combination group decreased(P＜0.01).Conclusions CAPE could increase the radiation sensitivity of HeLa cells by G2/M arrest and may be related to the inhibition of the sub-lethal damage repair.

Objective To investigate the efficacy and safety of whole brain radiotherapy combined with ectatinib hydrochloride in the treatment of non-small cell lung cancer (NSCLC) brain metastases. Methods A total of 44 patients with brain metastases from NSCLC from June 2013 to June 2017 were randomly divided into combination therapy group and radiotherapy group. The efficacy and safety between the two groups were compared. Results The median follow-up was 18.5 months. The mPFS of the combination therapy group and the radiotherapy group were 9.3 months and 6.6 months, respectively (log-rank P=0.006). The mPFS of the EGFR mutant and wild type in the combination group were12.2 months and 6.5 months (log-rank P=0.002). The mPFS of EGFR mutants and wild-type patients in the radiotherapy group were 6.4 months and 6.8 months, respectively (log-rank P=0.933). The mOS in the combination therapy group and the radiotherapy group were 14.2 months and 12.6 months, respectively (log-rank P=0.035). The mOS of the EGFR mutant and wild type in the combination group were 19.1 months and 12.7 months, respectively (log-rank P=0.006). The mOS of EGFR mutants and wild-type patients in the radiotherapy group were 12.6 months and 10.4 months, respectively (log-rank P=0.449).The ORR of the two groups was 78.3％ and 47.6％, respectively (log-rank P=0.035), and the DCR was 91.3％ and 85.7％, respectively (χ2=0.341, P=0.560).In terms of adverse reactions, the incidence of rash in the combined group was 56.5％, of which 3 cases were grade 3-4. The adverse reactions such as fatigue, nausea and vomiting, diarrhea, liver and kidney damage, and leukopenia were all grade 1-2, and there was no statistically significant difference between the two groups. Conclusion Ectinib hydrochloride combined with whole brain radiotherapy can improve the objective response rate of patients with non-small cell lung cancer with brain metastases, prolong the median local progression-free survival and median overall survival, and the patient's adverse reaction tolerance is good.

OBJECTIVE: To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models. RESULTS: The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C. CONCLUSION Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.
Humans ; Factor XII/genetics* ; Pedigree ; Mutation ; Mutation, Missense ; Heterozygote ; Factor XII Deficiency/genetics*

Objective To explore the appropriate target ranges of blood glucose in intensive insulin therapy (ⅡT) for acute hyperglycemia following traumatic brain injury (TBI).Methods A randomized,open-label and controlled clinical trial was performed on 208 patients,admitted to our hospitals from Junuary 2014 to Sepember 2016.They were divided into ⅡT group (n=156),who were subdivided into slight (10.1-13.0 mmol/L),moderate (7.1-10.0 mmol/L),and strict (4.4-7.0 mmol/L) control blood glucose groups (n=52),and non-ⅡT group (n=52).Survival analysis 6 months after treatment was performed by Kaplan-Meier method.Modified Rankin scale (mRS) scores and Barthel index (BI),Glasgow Outcome scale (GOS) scores,concentrations of lactic acid in cerebrospinal fluid (CSF) and glycosylated hemoglobin,Glasgow coma scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ) scores,Length of staying in intensive care unit (ICU) and incidence of adverse events were compared between the patients from different groups at different treatment times.Results Blood glucose level within 7 d of admission in patients ofⅡT group was in target ranges.The survival rate of patients from slight and moderate control blood glucose groups was significantly higher than that in the non-ⅡT group and strict control blood glucose group 6 months after treatment (x2=4.237,P=0.040;x2=5.621,P=0.018).As compared with those in the non-ⅡT group and strict control blood glucose group,the mRS scores 3 months after treatment were significantly decreased,and GOS scores and BI one,3 and 6 months after treatment were significantly increased in patients from slight and moderate control blood glucose groups (P＜0.05).As compared with that in the non-ⅡT group,and slight and moderate control blood glucose groups,the glycosylated hemoglobin level 7 d after treatment was significantly decreased in strict control blood glucose group (P＜0.05).As compared with those in the non-ⅡT group and strict control blood glucose group,the concentration of lactic acid in CSF 7 d after treatment,APACHE Ⅱ scores 7 and 14 d after treatment,length of staying in ICU and incidence of adverse events were significantly decreased in patients from slight and moderate control blood glucose groups (P＜0.05).The mean value of blood glucose in slight and moderate control blood glucose groups was (8.40±0.39) mmol/L.Conclusion Proper ⅡT improves the outcomes of TBI patients and (8.40±0.39) mmol/L are established as the target ranges in ⅡT for TBI.

Objective To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. Methods The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. Results The frequencies of HLA-A*0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4％vs 0.6％,χ2=10.788, P=0.001, Pc=0.016;7.5％vs 0％,χ2=69.850, P<0.0001);the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4％vs 16.1％,χ2=9.845, P=0.002, Pc=0.044;0％vs 3.1％,χ2=18.520, P<0.001). Conclusion The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.

Objective To study the relationship between HLA allele frequencies in peripheral blood mononuclear cells (PBMCs) and the susceptibility to tuberculosis in southern Chinese population. Methods The polymorphisms of HLA-A and HLA-DRB1 loci in the PBMCs were analyzed in 294 patients with active tuberculosis using polymerase chain reaction-sequence based typing (PCT-SBT). The allele frequencies in the patients were compared with the data from 644 control southern Chinese subjects obtained from the online database Allele Frequencies in Worldwide Population. Results The frequencies of HLA-A*0101 and HLA-DRB1*1454 alleles in the patient cohort with pulmonary tuberculosis were significantly higher than those in the control group (2.4％vs 0.6％,χ2=10.788, P=0.001, Pc=0.016;7.5％vs 0％,χ2=69.850, P<0.0001);the frequencies of HLA-DRB1*1202 and HLA-DRB1*1401 alleles were significantly lower in this patient cohort than in the control group (10.4％vs 16.1％,χ2=9.845, P=0.002, Pc=0.044;0％vs 3.1％,χ2=18.520, P<0.001). Conclusion The frequencies of HLA-A and HLA-DRB1 alleles are correlated with the susceptibility to active tuberculosis in this southern Chinese population. HLA-A*0101, HLA-DRB1*1454 and the other 3 alleles are likely susceptible genes to tuberculosis, while HLA-DRB1*1202, HLA-DRB1*1401 and the other 4 alleles can be protective genes in this population.