The ketogenic diet has been used for the treatment of epilepsy for 90 years, it also has been introduced to our country for more than 10 years.Its clinical efficacy has been recognized,but its antiepilepsy mechanisms are still unclear.This paper reviews its possible antiepilepsy mechanisms from the ion channels, neurotransmitters, neuroprotection, adenosine, mTOR signaling pathway and immune factors.

The function of the herpes simplex virus type 1(HSV-1)UL4 protein is still elusive. Our objective is to investigate the subcellular transport mechanism of the UL4 protein. In this study,fluorescence microscopy was employed to investigate the subcellular localization of UL4 and characterize the transport mechanism in living cells. By constructing a series of deletion mutants fused with enhanced yellow fluorescent protein(EYFP),the nuclear export signals(NES)of UL4 were for the first time mapped to amino acid residues 178 to 186. In addition,the N-terminal 19 amino acids are identified to be required for the granule-like cytoplasmic pattern of UL4.Furthermore,the UL4 protein was demonstrated to be exported to the cytoplasm through the NES in a chromosomal region maintenance 1(CRM l)-dependent manner involving RanGTP hydrolysis.

Objective To investigate the effects of inhalation of isoflurane at different time points on hypoxic-ischemic brain injury in neonatal rats.Methods One hundred and eighty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 6 groups (n =30 each):sham operation group (group Ⅰ),cerebral hypoxia/ischemia (H/I) group (group Ⅱ),and inhalation of isoflurane at different time point groups (groups Ⅲ-Ⅵ).Brain ischemia was induced by double ligation of left common carotid artery followed by inhalation of 8 ％ O2 + 92 ％ N2 for 2 h at 37 ℃.In groups Ⅲ,Ⅳ,Ⅴ and Ⅵ 1.5 ％ isoflurane was inhaled for 30 min starting from 0,3,6,12 h after H/I respectively,while the rats were exposed to 30％ O2 and 70％ N2 only in groups Ⅰ and Ⅱ.The survival rate at 7 days after H/I was recorded.The animals were sacrificed at 7 days after H/I.The brains were removed and the right and left cerebral hemispheres (CH) were weighed separately.The ratio between left/right CH was calculated.The density of normal neurons in ventral posterior inferior thalamic nucleus and posterior cingulate cortex in left and right CH were measured and the ratio of the density of normal neurons in the left to right CH was calculated.Results Compared with group Ⅰ,the weight of left cerebral hemisphere,ratio between left/right CH,and ratio of the density of normal neurons in the left to right CH were significantly decreased in other five groups (P ＜ 0.05).Compared with group Ⅱ,the weight of left cerebral hemisphere,ratio between left/right CH,and ratio of the density of normal neurons in the left to right CH were significantly increased in groups Ⅲ,Ⅳand Ⅴ (P ＜ 0.05).There were no significant differences in the indices nentioned above among groups Ⅲ,Ⅳand Ⅴ (P ＞ 0.05).There was no significant difference in the survival rate among groups Ⅱ-Ⅵ (P ＞ 0.05).Conclusion Inhalation of 1.5％ isoflurane for 30 min within 6 h after cerebral H/I can reduce the cerebral injury in neonatal rats.

Objective To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) an- tibody AE1/AE3 was applied to detect cytokeratin with Envision~(TM) method in routine pathological negative re- gion lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67% (4/6)in stage p-Ⅰ, p-Ⅱand p-Ⅲ, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the mierometastasis group in two groups, the survival rate difference was statistically significant. Comparing the annual survival rate and median sur- vival time in pCK-ⅢA stage with p-Ⅰ-Ⅱstage, pCK-ⅢA stage annual survival rate and median survival time was significantly different (P=0.020). Similarly, comparing the survival rate in pCK-ⅡB stage with p-ⅠB stage, pCK-ⅡB stage survival rate was significantly different(P=0.059). Comparing the survival time of pCK-ⅢA stage with p-Ⅲstage, pCK-ⅡB stage, with p-ⅡB stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions The rate of positive cytokeratin increase is ac- companied by the disease progress in NSCLC. Positive cytokeratin has disadvantagious prognosis. It is showed that pCK-N1 may be equal to p-N1 and pCK-N2 which also may be equal to p-N2. Micrometastasis may affect the UICC staging currently in use.

Objective:To observe the effect of attenuated-dose aflibercept in the treatment of retinopathy of prematurity(ROP).Methods:A non-randomized controlled study was conducted, and 76 eyes of 38 ROP pediatric patients treated in First Affiliated Hospital of Zhengzhou University from December 2018 to May 2020 were enrolled.According to the requirements of their guardians, the patients were divided into ranibizumab group with 42 eyes of 21 cases and attenuated-dose aflibercept group with 34 eyes of 17 cases, and received intravitreal injection of ranibizumab 0.025 ml (0.25 mg) or aflibercept 0.012 5 ml (0.5 mg) according to grouping respectively.Retcam fundus photography was used to observe the treatment response at 1 week, 2, 4 weeks and 2, 3, and 6 months after treatment, and the effective rate at the end of follow-up was calculated.The intraocular pressure was measured with Icare PRO magnetic rebound tonometer at 1 minute, 10, and 30 minutes after injection. The ocular and systemic complications were observed during the 6-month follow-up period.All the guardians signed the informed consent prior to treatment.This study was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2020-KY-228).Results:The effective rates of single ranibizumab and attenuated-dose aflibercept were 90.5% (38/42) and 88.2% (30/34), respectively, with no significant difference between the two groups ( χ2=0.10, P=0.75). The intraocular pressure of the ranibizumab group at 1 minute and 10 minutes after the operation were higher than those of the attenuated-dose aflibercept group, and the difference was statistically significant (both at P<0.01). The intraocular pressure recovered to the baseline level at 30 minutes after the operation.In the ranibizumab group, 4 eyes were ineffective after a single injection, among which 2 eyes were effective after second intravitreal injection of ranibizumab and 1 eye was effective after retinal laser photocoagulation treatment and 1 eye underwent vitrectomy due to the progress of retinal detachment one week after intravitreal injection, and the posterior retina reattached well.In the attenuated-dose aflibercept group, 4 eyes did not respond to treatment, of which 3 eyes were effective after second intravitreal injection of aflibercept, and 1 eye was effective after retinal laser photocoagulation.No ocular or systemic complications were observed during the followed-up period. Conclusions:Reduced dose of aflibercept is safe and effective in the treatment of ROP, and has little influence on intraocular pressure.

[ABSTRACT]OBJECTIVETo investigate the phoenix roebelenii pollen as the allergen of allergic rhinitis in Hainan Province and provide guidance for prevention and treatment of allergic rhinitits.METHODSA total of 2054 patients with allergic rhinitis were tested with the allergen of phoenix roebelenii pollen by skin prick test, and then choose 30 positive cases to give the nasal mucosa provocation test. RESULTSThe total positive rate of allergen of phoenix roebelenii pollen by skin prick test was 67.38% (1384/2054). The 30 cases with positive skin prick test were all positive in nasal mucosa provocation test and the cases in control group were all negative.CONCLUSIONPhoenix roebelenii pollen is an important allergen in Hainan Province. There is a correlation between skin prick test and nasal mucosa provocation test. The allergen skin prick test can provide clue for the patients to avoid the pathogenic allergens and for the specific immunotherapy.

ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4％,65.9％,21.0％ and 7.7％,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3％ and 28.7％,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.

Objective To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC).Methods Two hundred and one patients of stage Ⅳ NSCLC were enrolled from January,2003 to July,2010.Of the 182 patients eligible for analysis,The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75,respectively.Patients were treated by platinum-based chemotherapy,the median number of cycle was 4.The median dose to planning target volume of primary tumor (DTPTv) was 63 Gy.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years'follow up.Of 182 patients,the 1-,2-,and 3-year overall survival (OS) rate and median survival time (MST) was 41.0％,17.0％,10.0％ and 10.5 months,respectively ;with single-organ metastasis and multi-organ metastasis were 50％,20％,14％ and 13 months and 29％,12％,0％ and 8.5 months ( x2 =10.10,P =0.001 ),respectively; compared with multi-organ metastasis,the 1-,2-,and 3-year OS arte and MST of patients with bone,lung metastasis only was 58％,25％,16％ and 14 months (x2 =10.42,P=0.001 ) and 49％,21％,21％ and 11 months (x2 =6.39,P=0.011 ) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49％,8％,0％ and 12 months and 29％,12％,0％ and 8 months,respectively;x2 =0.71,P =0.401 ) ;the 1-,2-,and 3-year OS rate and MST was 63％,23％,19％ and 15 months and 42％,15％,0％ and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy ( x2 =6.47,P =0.011 ) ; for patients under the same metastasis and 4 - 5 cycles of chemotherapy,no matter whether single-organ or multiple-organ metastases,the 1 -,2-,3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy ( DTPTV ＜ 63 Gy ) ( 71％,25 ％,25％ and 16.8 months and 33％,17％,0％ and 10.5 months,respectively;x2 ＝4.73,P =0.030 ;54％,21％,0％ and 14.3 months and 29％,10％,0％ and 7.6 months,respectively,x2 =8.16,P =0.004).The MST of liver metastases was 6 months,there was significantly difference when comparing with non liver matastasis ( x2 =17.21,P =0.000).Conclusions It is very important to treat stage Ⅳ NSCLC with CCTTRT,especially patients with single-organ metastasis.Liver metastases is a unfavorable prognostic factor.

Objective To evaluate the overall survival and safety among patients for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to July 2010,201 patients with stage Ⅳ NSCLC were included.All patients were treated with CCTTRT.Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity.One hundred and eighty-two patients were eligible for survival analysis.All patients received platinum-based two-drug chemotherapy.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV ) was 63 Gy.Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria.Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Cox regression model was used to examine the effect of CCTTRT on overall survival.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up,respectively.Of the 182 patients eligible for survival analysis,further stratified analysis showed that the 1-,2-and 3-year overall survival rate and median survival time (MST) was 54％,20％,13％ and 14.3 months,respectively for patients treated with concurrent 4 -5 cycles chemotherapy and CCTTRT,and 66％,23％,19％ and 16.1 months,respectively for those treated with 4 -5 cycles chemotherapy and DTPTV ≥ 63 Gy.Under similar chemoradiotherapy intensity,the MST of patients with single organ metastasis was significantly longer than that with multiple organ metastases ( 13.0 months versus 8.5 months,x2 =10.10,P =0.001 ).For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy,MST of patients treated with DTPTV≥63 Gy was significantly longer than those treated with DTPTV ＜63 Gy[14.9 months vs.8.4 months (x2 ＝20.48,P =0.000) and 16.1 months vs.8.8 months ( x2 =11.75,P =0.001 )].For patients with single organ metastasis,MST was 16 months for those treated with DTPTV ≥63 Gy and 9 months for those with DTPTV ＜63 Gy (x2 =10.51,P=0.000) ;for patients with multiple organ metastasis,it was 11 months and 7 months,respectively ( x2 =7.90,P =0.005 ).Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243,P=0.019) and improved KPS (β =1.268,P=0.000) were independent factors for survival.For the whole group,45％ patients had Grade 2 -3 gastrointestinal toxicity,35.0％ grade 3- 4 leukopenia,18％ grade 3- 4 thrombocytopenia.15.0％ grade 3- 4 anemia,9.5％ Grade 2 - 3 radiation pneumonia and 13.4％ radiation esophagitis,respectively.Conclusions For stage Ⅳ NSCLC,CCTTRT can prolong survival time with acceptable toxicity.Radiotherapy to thoracic primary tumor should be under consideration.

Objective To evaluate the importance of three-dimensional radiotherapy for elderly patients of stage Ⅳ non-small cell lung cancer (NSCLC).Methods Comparing with treatment outcome of ≥65 years 67 patients and ＜ 65 years 134 patients using concurrent chemotherapy and thoracic threedimensional radiotherapy during 2003 to 2010 years.Survival analysis was taken by Kaplan-Meier method.The multivariate prognosis was analyzed by Cox model.Results The follow-up was 97.8％.The percentage of ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy were 30％ and 55％,and with 42％ and 49％ patients with radiotherapy ≥63 Gy.The median survival time (MST) were 17 months and 14 months (x2 =0.76,P =0.384) for ≥65 years and ＜ 65 years patients accepted with concurrent 4-5 cycles chemotherapy concurrent ≥63 Gy radiotherapy respectively.The MST and 1-,2-,3year overall survival rate were 17 months and 8 months,65％ and 23％,30％ and 13％,24％ and 9％(x2 =7.90,P =0.005) for whole groups patients treated with chemotherapy concurrent ≥63 Gy and ＜ 63 Gy radiotherapy.And the MST of patients ≥ 63 Gy was significantly longer than those with ＜ 63 Gy either concurrent chemotherapy any cycles (x2 =9.54,P =0.023).The MST were 14 months and 8 months (x2 =1.82,P=0.178),17 months and 17 months (x2 =0.47,P=0.492) for ≥ 65 years and ≥ 63 Gy radiotherapy patients accepted with concurrent 4-5 cycles and 2-3 cycles chemotherapy concurrent respectively.Multivariate analysis showed local response (β =0.600,P =0.003) and numbers of tumor metastasis (β =0.670,P =0.040) were independent factors for survival.Conclusions For a part of elderly patients of stage Ⅳ NSCLC,concurrent chemotherapy and thoracic three-dimensional radiotherapy can prolong survival time with acceptable toxicity.Perhaps radiotherapy is more important.