Approximately 70% epilepsy may be associated with genetic etiology. To date, more than 2 900 genes related to epilepsy have been reported, and genotype-phenotype association in epilepsy has received increasing attention. Explaining how mutations in the same gene can lead to different diseases or phenotypes remains challenging. Sub-molecular mechanisms, including functional structural domains, amino acid substitutions, isoforms, and monoallelic/biallelic mutations, provide new perspectives for deciphering genotype-phenotype association in epilepsy. This review summarizes the role of sub-molecular mechanisms in genotype-phenotype association in epilepsy, to provide new strategies for clinical diagnosis and precise treatment of epilepsy.

Approximately 70% epilepsy may be associated with genetic etiology. To date, more than 2 900 genes related to epilepsy have been reported, and genotype-phenotype association in epilepsy has received increasing attention. Explaining how mutations in the same gene can lead to different diseases or phenotypes remains challenging. Sub-molecular mechanisms, including functional structural domains, amino acid substitutions, isoforms, and monoallelic/biallelic mutations, provide new perspectives for deciphering genotype-phenotype association in epilepsy. This review summarizes the role of sub-molecular mechanisms in genotype-phenotype association in epilepsy, to provide new strategies for clinical diagnosis and precise treatment of epilepsy.

Objective:To compare and analyze the efficacy and safety of intraoperative radiotherapy (IORT) combined with conventional therapy (surgery combined with radiochemotherapy) and conventional therapy alone for pancreatic cancer.Methods:Literature review was conducted from PubMed, Cochrane Library, Web of Science, Embase, Chongqing VIP, CNKI, Wanfang Data and China Biomedical Literature Service System (SinoMed). The literatures that met the inclusion criteria were screened and the data were extracted. Meta-analysis was carried out by RevMan 5.4 software.Results:A total of 11 studies consisting of 813 patients were included. According to the combined results, compared with conventional therapy, IORT combined with conventional therapy could improve the overall survival rate of pancreatic cancer ( HR=0.66, 95% CI=0.54-0.81, Z=4.03, P<0.001), and did not increase the treatment-related side effects ( OR=1.00, 95% CI=0.69-1.46, Z=0.01, P=0.99), but failed to bring benefit to the local control rate ( HR=0.56, 95% CI=0.31-1.01, Z=1.93, P=0.05). Conclusions:The overall survival rate in the IORT combined with conventional therapy group is significantly better than that in the conventional therapy group. No significant difference is found in the treatment-related adverse reactions between two groups. IORT combined with conventional therapy is worthy of clinical application.

Objective:To investigate the effect of heat shock protein 90 (Hsp90) inhibitor PU-H71 combined with X-ray on radioresistant human cervical cancer cells.Methods:The expression levels of Hsp90 gene between cervical cancer tissues and adjacent tissues were analyzed by bioinformatics. Radioresistant cervical cancer cell lines HeLa RR and SiHa RR were obtained by fractional irradiations (2 Gy per fraction, 30 fractions). The cell lines were divided into the control group (treated with dimethyl sulfoxide), irradiation alone group, PU-H71 group (treated with 0.5 μmol/L PU-H71), and PU-H71+irradiation group (irradiation at 24 h after treatment with 0.5 μmol/L PU-H71). Cell survival was detected by clonal formation assay. Immunofluorescence assay was used to detect γH2AX foci at 1, 6, and 24 h after cell treatment. The expression level of Rad51 protein at 1, 2, 6, 12, and 24 h after cell treatment was detected using Western blot. The expression level of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) was measured at 2 h after cell treatment. Cell apoptosis at 48 h after cell treatment was assessed by flow cytometry. Results:PU-H71 enhanced the sensitivity of radioresistant cervical cancer cells to X-ray. Compared with the irradiation alone group, the radiation sensitization ratios (SER) of HeLa RR and SiHa RR cells at 10% survival were 1.36 and 1.27, and the apoptosis rates were increased by approximately 72.1% and 63.1% in the PU-H71+irradiation group, respectively. PU-H71 delayed the duration of γH2AX foci induced by X-ray, inhibited the phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), thus preventing non-homologous end joining (NHEJ) repair and delaying homologous recombination repair.Conclusion:PU-H71 increases the radiosensitivity of radioresistant cervical cancer cells by inhibiting the repair pathway of DNA double-strand break, which is expected to be a radiosensitizer to enhance the efficacy of radiotherapy for cervical cancer.

ObjectiveTo analyze the feasibility， reliability and validity of the disability assessment for dementia scale for the elderly. MethodsA total of 290 dementia patients from 17 survey sites in 13 districts and counties of Chengdu were enrolled by convenient sampling method， and they were assessed using demographic data inventory， Mini-Mental State Examination （MMSE）， Neuropsychiatric Inventory （NPI）， Physical Self-Maintenance Scale （PSMS） and disability assessment for dementia scale for the elderly. Cronbach's α coefficient， Spearman-Brown coefficient， Guttman split-half coefficient and test-retest reliability were used to evaluate the internal consistency of above scales. Criterion-related validity of the scale was analyzed based on MMSE， NPI and PSMS. ResultsA total of 276 patients （95.17%） completed valid questionnaires. The intraclass correlation coefficient of the total score and each dimension were between 0.828~0.976， the Spearman-Brown coefficient were between 0.790~0.917， the Guttman split-half coefficient were between 0.812~0.857， and the Cronbach’s α coefficient were between 0.737~0.886. The cognitive function dimension score was positively correlated with the MMSE score （r=0.948， P<0.01）， the mental behavior symptom dimension score was positively correlated with the NPI score （r=0.893， P<0.01）， and the daily living ability dimension score was positively correlated with the PSMS score （r=0.997， P<0.01）. The dimensions scores were positively correlated with the total score of the scale （r=0.634~0.841， P<0.05）. ConclusionDisability of dementia assessment scale has good feasibility， reliability and validity， which is a reliable tool to assess senile dementia and disability.

Objective: To evaluate the efficacy of ginsenoside Rg3(GRg3) in the treatment of acute radiation proctitis in rat models. Methods: On the 7^th day after 21.5 Gy irradiation, 100 rats were divided into the control group (normal saline, n=20), GRg3 group (gavage of 20 mg/kg, 40 mg/kg and 80 mg/kg GRg3, n=20 for each dose) and Smecta mixture enema group (n=20). After 2 weeks, all rats were anesthetized with chloral hydrate (3 ml/kg) and approximately 5 ml of blood sample was collected from the abdominal aorta prior to sacrifice. The rectal tissues were taken and prepared for detection of Bax and NF-κB contents and HE staining to observe the pathological changes of the rectal tissues. After the blood samples were centrifuged, the supernatants were collected for ELISA to detect the serum levels of IL-2, IL-6, TNF-α and MPO in each group. Results: In the GRg3 group, the serum inflammatory cytokines, serum MPO concentration and the concentration of Bax and NF-κB in the intestinal tissues of rats were decreased along with the increasing dose of GRg3. These parameters in the high-dose GRg3 group were significantly lower than those in the saline group (all P<0.05), whereas did not significantly differ from those in the Smecta mixture enema group (all P>0.05), suggesting that GRg3 exerted good therapeutic effect on acute radiation proctitis in rat models. Conclusions GRg3 can significantly reduce the concentration of inflammatory cytokines, Bax and NF-κB in the intestinal tissues of rat models with acute radiation proctitis, which is more efficacious than the normal saline. GRg3 can be used to treat acute radiation proctitis in rat models.

Objective To systematically review the efficacy and safety of postoperative radiotherapy and postoperative chemotherapy for patients with endometrial cancer,which may give support for clinical proper selection.Methods The randomized controlled trials (RCTs)comparing postoperative radiotherapy with post-operative chemotherapy for patients with endometrial cancer were searched in EMBase,PubMed,Cochrane Library,Chinese Biomedical Literature Data,China National Knowledge Infrastructure,and VIP database from the inception to August 201 5.Two reviewers independently assessed the quality of included studies and extrac-ted data.We analyzed the statistic data using RevMan 5.1 software.Results Three RCTs concluding 1 1 21 patients were included.Meta analysis showed that there were no significant differences between the two groups in five-year survival rate (RR =0.94,95%CI:0.80-1 .1 0,Z =0.77,P =0.440),five-year progression-free survival rate (RR =0.98,95%CI:0.90-1 .07,Z =0.52,P =0.61 0)and recurrence rate (RR =1 .06, 95%CI:0.91 -1 .24,Z =0.75,P =0.450),but there were significant differences between the two groups in grade 3-4 thrombocytopenia (RR =0.1 3,95%CI:0.07-0.27,Z =5.62,P <0.000 01 )and grade 3-4 neu-tropenia (RR =0.01 ,95%CI:0.00-0.03,Z =8.27,P <0.000 01 ).Subgroup analysis showed that there were significant differences between the two groups in five-year survival rate (RR =0.79,95%CI:0.68-0.91 , Z =3.1 5,P =0.002)and five-year progression-free survival rate (RR =0.82,95%CI:0.69-0.97,Z =2.31 ,P =0.020)for patients with Ⅲ-Ⅳ stage endometrial cancer.Conclusion Current evidence indicates that compared with postoperative radiotherapy,postoperative chemotherapy may improve the survival rate for pa-tients with advanced stage endometrial cancer.The long-term curative effects still need to be confirmed by RCTs with high quality and large sample.

Objective To investigate the effect of pregnancy on the potency of bupivacaine for spinal anesthesia in rats. Methods Female non-pregnant SD rats weighing 180-220 g and 17 day pregnant SD rats weighing 350-400 g were used in this study. The rats ( 18 non-pregnant, 18 pregnant) in which PE-10 catheter were successfully placed without complications were selected. The 18 non-pregnant rats were randomly divided into 3 groups (n =6 each): control group (group C), 2% bupivacaine group (group B2 ) and 4% bupivacaine group (group B4). The 18 pregnant rats were also randomly divided into 3 groups (n = 6 each): control group (group PC),2% bupivacaine group (group PB2 ) and 4% bupivacaine group (group PB4 ). Group C and PC received intrathecal (IT) normal saline 30 μl, and the other 4 groups received 2% or 4% bupivacaine 30 μl intrathecally. Analgesia was determined using the taifllick latency (TFL) before IT administration (baseline), and at 10 min, 20 min,30 min, 1 h, 2 h, 4 h, 1 d, 2 d, 3 d and 4 d after IT administtation. The percentage of the maximal possible effect (MPE) was calculated. Hind-limb motor function (MF) was also assessed. Results Compared with the baseline value, MPE at 10 min-2 h after administration and MF scores at 10 min-1 h after administration were significantly increased in group B2, MPE at 10 min-4 h after administration and MF scores at 10 min-1 h after administration were significantly increased in group B4;MPE at 10 min-1 d after administration and MF scores at 10 min2 h were significantly increased in group PB2 and MPE at 10 min-1 d after administration and MF scores at 10 min4 h were significantly increased in group PB4 ( P ＜ 0.05 ). Conclusion Pregnancy can enhance the potency of bupivacaine for spinal anesthesia in rats.

Objective To evaluate the toxicity and efficacy of carbon ion radiotherapy for cutaneous malignant melanoma. Methods Form December 2006 to May 2009, 13 patients with superficial malignant melanoma were treated with carbon ion radiotherapy in the Institute of Modern Physics, Chinese Academy of Sciences. The total dose was 60 -66 GyE in 6 -12 fractions within 6 -12 days. The disease was Stage Ⅱ_a in 2, Ⅱ_b in 3, Ⅱ_c in 5, and Ⅲ_c in 3 patients. The toxicities were assessed according to the Radiation Therapy Oncology Group (RTOG) criteria, and the efficacy was evaluated with WHO criteria. Results The median follow-up time was 13.5 months (range, 1 -25 months) and the follow-up rate was 100%. Of the 13 patients, 10(77%) achieved complete remission (CR), and 3(23%) partial remission (PR). The overall response rate (RR) was 100%, and the median survival time was 21.3 months (95% CI, 18. 1 -24.5 months). The grade 0, 1,2 and 3 skin reaction occurred in 3, 6, 2 and 2 patients, respectively. The hematologic toxicities were mild. Conclusions Carbon ion radiotherapy is a safe and effective treatment for cutaneous malignant melanoma.

Objective The study is designed to evaluate the difference in identification for depression and clinical effectiveness of its treatment between psychiatrists and non-psychiatric Dhysieians at out-patient departments of general hospitals and to analyze its related factors.Methods Totally,680 patients who visited psychiatric clinics in nine general hospitals of Shanghai at first time were screened by psychiatrists using Composite International Diagnostic Interview(CIDI)for depression and the screening resuhs were compared to the diagnosis made by non-psychiatric physicians as goal-keepers there.Altogether 297 patients with depression were recruited and assessed using Hamilton Depression Rating Scale(HAMD)and Hamilton Anxiety Rating Scale(HAMA).A self-made questionnaire for basic information was used to assess the ability for identification of depression in non-psychiatric physicians of general hospitals.Results Psychiatrists identified depression correctly in 337 of 680 patients who visited psychiatric clinics in general hospitals at their first visit,but non-psychiatric physicians only identified 216 patients,with statistically significant difference(χ2=30.73,P=0.000).A consistent agreement on depression diagnosis between the findings by psychiatrists and by CIDI was reached with Kappa of 0.774,but Kappa for that between the findings by non-psychiatric physicians and CIDI was 0.439.Effectiveness of treatment for depression by psychiatrists was better than that by non-psychiatric physicians,with higher total score and scores for each item of HAMD four,eight and 12 weeks after treatment,respectively(P＜0.05 or P＜0.01).Length of professional work of non-psychiatric physicians and annual time for professional training in management of mental disorders associated with their ability of identification for depression(P＜0.05).Conclusion Ability of non-psychiatric physicians to identify alQd cope with depression in the psychiatric department of general hospitals was insufficient,suggesting that more importance should be attached to the management of service quality at psychiatric department of general hospitals.