Hepatocellular carcinoma has a high morbidity and mortality, which has seriously harmed human health. Several targeted therapies have been approved for the first- and second-line treatment of advanced hepatocellular carcinoma. The emergence of immunotherapy has brought the treatment of hepatocellular carcinoma into a new era. Targeted and immunotherapeutic agents have synergistic effects in mechanism, also the combination of these two therapies has been clinically beneficial to patients with advanced hepatocellular carcinoma. At the same time, in addition to the systemic therapy of targeted combined immunological, applying appropriate local therapy can provide a longer survival period or even a chance of cure for that some patients. The authors introduce the diagnosis and treatment of a case of advanced hepatocellular carcinoma who achieved pathological complete remission by first-line immunotherapy combined with anti-angiogenesis targeted therapy.

Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer (SCLC) specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E (n= 5) ,V600A (n= 2) ,V600M (n= 1) ,D594G (n= 1),G464E (n= 1),K601R (n= 2) and S605N (n= 1).KRAS mutation was detected in 6 cases including G12C (n= 3),G12A (n= 1),G12D (n=1) andG13D (n= 1).PIK3CA mutation was observed in 4 samples including E545G (n= 2) and H1047R (n= 2).Besides,NRAS mutation (Q61R) was detected in 1 case and MEK1 mutation (D61Y) was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was (10.30±0. 751) months (95％CI:8. 829-11. 771 months),significantly shorter than (12.80±0. 543) months (95％CI:11. 736-13. 864 months) of their counterparts without gene mutation (P=0. 011). Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

Objective To explore the regulation and mechanism of Cav1.2 current by KCNE1. Methods Transient transfection was used to transfer Cav1.2 channel plasmids separately or together with KCNE1 plasmids into HEK293 cells. The experiment was divided into 2 groups (15 cells in each group):Cav1.2 group, Cav1.2+KCNE1 group.The whole-cell patch clamp technique was used to record Cav1.2 current and gating dynamics. Results After co-transfection of KCNE1 with Cav1.2, Cav1.2 current decreased significantly. At 0 mV, peak current density of Cav1.2 was reduced from (-14.8±2.5) pA/pF to (-7.5±1.6) pA/pF (n=15, P<0.01). Based on the gate control mechanism, it is found that the regulation of Cav1.2 current by KCNE1 mainly makes the steady-state inactivation curve of the channel shifted to a more negative direction, thus accelerating the inactivation. Meanwhile, the recovery process of the channel after inactivation is slowed down and the recovery time constant was prolonged. Conclusions The KCNE1 subunit can reduce the current density of Cav1.2 by changing the channel inactivation and recovery process.

Epidermal growth factor receptor (EGFR) is a multi-functional receptor distributed throughout the metazoa. Study on its ligands so far remained mainly on mammals, including how ligands are processed into active forms, their interaction with EGFR, and the signaling pathway they induce. However, in invertebrates, ligands are more divergent among species. Currently, except for Drosophila, less is known about the insect EGFR ligands. Here, we identified two EGFR ligands in Bombyx mori by homology search, domain prediction, analysis of the potential translation initiation sequence and construction of phylogenetic tree, termed as BmEGF-1 and BmEGF-2. BmEGF-1 shows the greatest similarity to Drosophila Spitz and their Rhomboid-recognition motifs are highly identical. BmEGF-2 is a homolog to Drosophila Vein. Then we purified BmEGF-1 extracellular domain expressed in E. coli, and performed pull-down assay with BmEGFR extracellular domain secreted by Sf9 cells. The result confirmed their interaction. Lastly, we found the phosphorylation level of ERK and p38 MAPK was elevated after expression of BmEGF-1 in BmE cells, which suggested that BmEGF-1 is not only able to activate the canonical ERK signaling pathway, but may participate in other cellular processes by inducing p38 MAPK signaling pathway. Our study provides reference to further study of the biological function of BmEGF in silkworm.

Objective T o investigate the expression of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (H C N 4) and connexin43 (C x43) in the sinoatrial node of electric shock death. Meth-ods As experim ental group, 34 cases of electric shock death who had definite current m ark evidence were selected from pathology departm ent of X uzhou M edical C ollege from 2010 to 2013. As the control group, 20 cases of fatal severe craniocerebral injury in traffic accidents were chosen. T he expressions of H C N 4 and C x43 in the sinoatrial node were observed by im m unohistochem ical technology. Results H C N 4 positive cells expressed in the cell m em brane and cytoplasm of the sinoatrial node. C x43 positive cells expressed in the cell m em brane and cytoplasm of T cells and m yocardial cells. T he expression of H C N 4 was significantly higher than that of the control group (P<0.05) and the expression of C x43 was signifi-cantly lower than that of the control group (P<0.05). Conclusion T he changes of H C N 4 and C x43 ex-pressions in the sinoatrial node illustrate electric shock death m ight be related to the abnorm alities of cardiac electrophysiology and conduction.

PurposeTo probe into the feasibility of small field of view intravoxel incoherent motion (IVIM) MRI in the grading of cervical cancer before surgery.Materials and Methods Twenty-three patients with cervical cancer confirmed pathologically underwent preoperative conventional MRI and IVIM sequence scan [IVIM sequence included 10 b value (0-1500 s/mm2)]. Based on postoperative pathological cell morphology the patients were divided into well differentiated group (10 cases) and moderately or poorly differentiated group (13 cases). Then the parameters such as the ADC standard, D value, D* value and f value were calculated in each group according to double exponential function analysis. The data in the two groups were compared and nonparametric test to see whether they had normal distribution.Results Compared with the well differentiated group, the moderately or poorly differentiated group had statistically lower ADC standard value and D value (t=140.5 and 129.5,P<0.05); the area under the D value curve was 0.965 and 0.854, respectively. The sensitivity and specificity of well differentiated group and moderately or poorly differentiated group were 88.9%, 100.0% and 77.8%, 81.8%, respectively. There was no difference in either D* value or f value between the two groups (t=-0.184 and 1.072,P>0.05).Conclusion Small field of view IVIM MRI is feasible in predicting the differentiation of tumor in the preoperative grading of cervical cancer.

Objective To study the effects of toys for laboratory animals on reproductive performance and growing development of experimental mice.Methods ICR mice were fed with toys, the informations of reproductive performance and growing development were recorded.Results All the data of reproductive performance of the test group were higher than the control group except the number of newborn mice, and showed significant difference ( P <0.05 ) .The data of growing development of the test group were higher than the control group too, but showed no significant difference ( P >0.05).Conclusion Toys for laboratory animals have good effects on reproductive performance and growing development of mice, and suggested to be used into the process of experimental mice raising.

Objective To study whether the green fluorescent protein ( GFP) gene can be successfully expressed in green fluorescent nude mice and the tissue distribution characteristics.Methods Small animal imaging system and RT-PCR assay were used to detect the GFP tissue distribution and fluorescence expression level.Results The GFP can be expressed in multiple tissues in green fluorescent nude mice.A higher expression was observed in the pancreas, heart, brain, and skin.Conclusion Exogenous GFP can be stably expressed and inherited in green fluorescent nude mice, with the highest expression in the pancreas.

Objective:To determine the immunological effects of a new type adjuvant CTA 1-DD/IgG.Methods:Intranasal im-munization of BALB/c mice with OVA in combination with adjuvant CTA 1-DD or CTA1-DD/IgG.Blood samples were subjected to OVA-specific IgG Abs detection and IgG subclass profiles assessment using ELISA.Splenic plasma cells secreting anti-OVA Abs were detected by ELISPOT.Results:CTA1-DD/IgG showed stronger activity in inducing OVA-specific IgG Abs and splenic Abs-secreting cells compared with CTA1-DD.The enhancement of IgG1,IgG2a and IgG2b Abs were observed,and the ratio IgG2a/IgG1 were >1 in both groups.Conclusion: CTA1-DD/IgG can exert enhanced adjuvant effects compared with CTA 1-DD.Mixed IgG subclasses are induced,indicating a more balanced Th1/Th2 response.

Objective To study the extracranial scalp electroencephalography ( EEG ) and intracranial electrocorticography (ECoG) of closed colony New Zealand white rabbits .Methods To record the extracranial scalp EEG and intracranial ECoG of closed colony New Zealand white rabbits , and to compare and analyze the results of those two scanning methods .Results EEG was characteristic of 9-12 c/sαwave and 16-20 c/sβwave with an amplitude of 30-100μV as the basic rhythm .ECoG showed 10-12 c/s αwave and 16-20 c/s βwave with an amplitude of 200-300 μV as the basic rhythm.Anesthesia could attenuate the electrocerebral activity , cause brain tissue hypoxia , and induce δ wave and slow θ wave in ECoG .Conclusions EEG method is a simple , non-invasive and convenient operation , and can be made in rabbits without anesthesia .The recorded EEG waveform is highly consistent with that of ECoG , and may be used as an alternative to the traditional ECoG in neurofunctional studies .