Hepatitis C virus(HCV)is the major etiology of non-A,non-B hepatitis.At present,neither a vaccine nor any effective therapy is available.Multi-epitope DNA vaccine(minigenes/epigenes)is a novel nucleic acid vaccine which can induces high effective cellular and humoral immune responses and has good perspective in clearing Hepatitis C virus through screening and assembling optimal antigen epitope genes(T cell、B cell epitope included).It is advanced in covering more HCV subtypes,inducing comprehensive anti-HCV immune responses and reducing the negative influence caused by irrelevant,disturbing and suppressive sequence as far as possible through selecting the most potential protective epitopes in DNA vaccine design.The recent research progress on HCV compound multi-epitope DNA vaccine and future prospects were reviewed.

Objective:To detect the value of utilizing bpMRI in prostate biopsy in the detection of prostate cancer with PSA≤20ng/ml.Methods:The clinical data of 394 patients who underwent prostate biopsy in the First Affiliated Hospital of Nanjing Medical University from November 2017 to October 2019 were retrospectively analyzed. Of all the patients, 177 underwent modified systematic biopsy, named TRUS group, 217 patients accepted pre-biopsy bpMRI examination, undergoing modified systematic biopsy if Prostate Imaging Reporting and Data System (PI-RADS) score < 3 or MRI-TRUS cognitive fusion targeted prostate + systematic biopsy if PI-RADS score ≥ 3, named MRI group. The median age of TRUS group was 66 (61, 74) years old, prostate specific antigen (PSA) was 9.52 (7.26, 12.30) ng / ml, and prostate volume (PV) was 36.84 (28.95, 57.72)ml. The median age of MRI group was 66 (59, 72) years old, PSA was 8.84 (6.65, 12.16) ng/ml, and PV was 39.45 (29.25, 58.69)ml. There was no difference in above parameters between the two groups. The χ 2 test was used to compare the detection rate of prostate cancer and clinically significant prostate cancer (CsPCa) between the two groups. Results:There was no significant difference in the detection rates of prostate cancer between TRUS group and MRI group [51.41% (91/177) vs. 48.39% (105/ 217), P = 0.550], but the detection rates of CsPCa were significantly different [26.55% (47/177) vs. 36.41% (79/217), P = 0.037]. In patients with PSA ≤ 10 ng / ml, there was no significant difference in the detection rates of prostate cancer between the two groups [43.62% (41/94) vs. 43.08% (56/130), P = 0.936], but there was a significant difference in the detection rates of CsPCa [17.02% (16/94) vs. 28.46% (37/130), P = 0.047]. There was no significant difference in the detection rates of prostate cancer [60.24% (50/83) and 56.17% (48/87), P= 0.504] and the detection rates of CsPCa [37.35% (31/83) vs. 48.28% (42/87), P = 0.150] between the two groups. The total detection rates of the last two needles in TRUS group and MRI group were 23.16% (41/177) and 36.63% (86/217), respectively, with significant difference ( P=0.001); the detection rates of CsPCa in the last two needles were 11.86% (26/177) and 29.03% (63/ 217), respectively, with significant difference ( P < 0.001). In MRI group, the detection rates of prostate cancer in patients with PI-RADS score <3, 3, 4, 5 were 21.21% (7/33), 25.84% (23/89), 73.24% (52/71), 95.83% (23/24), respectively; the detection rates of CsPCa were 12.12% (4/33), 17.98% (16/89), 54.93% (39/71), 83.33% (23/24), respectively. Conclusions:In patients with PSA ≤ 20 ng / ml, prostate biopsy based on bpMRI may improve the detection of CsPCa, especially in patients with PSA ≤ 10 ng/ml.

Objective To explore the changes of S - 100? protein in cerebrospinal fluid and serum of children with viral encephalitis and its clinical significance. Methods The levels of S - 100? protein of cerebrospinal fluid and serum of 36 children with viral encephalitis and 20 lumbar anesthesia children without central nervous system diseases were measured by enzyme - linked immunosor bent assay. Differences in the levels of cerebrospinal fluid and serum S-100? protein between children with and without coma, with and without convulsion, with and without sequelae in the case group were compared. Results S-100? protein levels of cerebrospinal fluid in the case group and control group were (0.641?0.390) and (0.037 ? 0.014) ?g/L( P

BACKGROUND: Some studies have presented that vascular endothelial growth factor and its receptor system may take part in onset and development of diabetic nephropathy (DN).OBJECTIVE: To further verify the interventional effects of irbesartan on vascular endothelial growth factor (VEGF) and its Flk-1 receptor expressions in kidney of diabetes mellitus (DM) rat, and the possible mechanism of irbesartan.DESIGN: Randomized control animal study.SETTING: West China Hospital of Sichuan University.MATERIALS: Eighteen male closed colony SD rats weighing 150-200 g were cared in standardization.METHODS: This study was performed at Laboratory of West China Hospital of Sichuan University from August 2006 to April 2007. All rats were randomly divided into a DN group, an irbesartan group and a normal control group, with 6 rats in each group. 10 g/L streptozotocin (55 mg/kg) was intraperitoneally injected to establish models; rats in the control group were administrated with the same dosage of citric acid buffer solution; rats in the irbesartan group were administrated with 3 mg/(kg·d) irbesartan after model establishment. VEGF and FIk-1 expressions were detected using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry technique; while, urine protein level, area and volume of renal glomerulus were detected, and correlations of data were analyzed.MAIN OUTCOME MEASURES: ①Renal pathological indicators, urine protein level, area and volume of renal glomerulus; ②VEGF and Flk-1 expressions;③renal immunohistochemical examination;④ correlation analysis.RESULTS:① Renal pathological examination by HE staining indicated that renal glomerulus was remarkably enlarged in the DN group; mesangial matrix was increased; mesangial cells were also increased; renal tubule was expanded. The lesions in the irbesartan group were milder compared to the DN group. Urine protein level in the DN group was significantly higher compared to the control group (P ＜ 0.01); renal weight/body mass, area and volume of renal glomerulus were significantly higher compared to the control group (P ＜ 0.01); urine protein level, renal weight/body mass, area and volume of renal glomerulus in the irbesartan group were significantly lower compared to the DN group (P ＜ 0.01). ② By the 16th week,VEGF and Flk-1 expressions in the DN group were significantly up-regulated compared to control group (P ＜ 0.05); while,VEGF and Flk-1 expressions in the irbesartan group were also up-regulated compared to the control group by the 16th week (P ＜ 0.05) but down-regulated compared to the DN group (P ＜ 0.05). ③ VEGF staining in the DN group was darker compared to control group (P ＜ 0.01), while the staining in the irbesartan group was also darker compared to the control group (P ＜0.01), but the staining in the irbesartan group was lighter compared to the DN group (P ＜ 0.01). Flk-1 staining was similar to the VEGF. ④ VEGF and Flk-1 were positively correlated, with urine protein level, area and volume of renal glomerulus (P ＜0.05).CONCLUSION: VEGF and its Flk-1 receptor play important roles in DN pathogenesis. Over expressions may cause renal injury, but irbesartan (angiotensin Ⅱ receptor antagonist) has the protective effects on kidney through inhibiting abnormal expression of VEGF and Flk-1.

A simple model organism Caenorhabditis elegans has contributed substantially to the fundamental researches in biology. In an era of functional genomics, nematode worm has been developed into a multi-purpose tool that can be exploited to identify disease-causing or disease-associated genes, validate potential drug targets. This, coupled with its genetic amenability, low cost experimental manipulation and compatibility with high throughput screening in an intact physiological condition, makes the model organism into an effective toolbox for drug discovery. This review shows the unique features of C. elegans, how it can play a valuable role in our understanding of the molecular mechanism of human diseases and finding drug leads in drug development process.
Animals ; Caenorhabditis elegans ; Drug Discovery ; Drug Evaluation, Preclinical

Objective To explore the roles of macrophage inflammatory protein-1?(MIP-1?)in hypoxic-ischemic encephalopathy(HIE)of newborn infarnts.Methods Serum samples were obtained in 24,72 h and 7 d after birth respectively from 34 newborn infants with HIE,and 20 newborn infants without HIE as control group.Enzyme-linked immunosorbent assay(ELISA)method was used to determine the serum concentrations of MIP-1?.Results Levels of MIP-1? in newborn infants with HIE [(12.47?2.51)ng/L]were significantly higher than that of newborn infants without HIE [(8.63?2.63)ng/L](P0.05).Conclusions MIP-1? are involved in HIE of neonates,and the more severe damage,the higher levels in serum,which suggests that,as an inflammatory mediator,the MIP-1? may play an important role in involvement of brain hypoxic-ischemic damage.

Objective:To construct a DNA vaccine co-expressing the HBV compound multi-epitope antigen gene, the hIL-12 and the anti-HBV siRNA genes, and to express this DNA vaccine in HepG2 cells. Methods:The HBV multi-epitope antigen gene was designed and synthesized before it was fused with enhanced green fluorescent protein(EGFP) gene, and cloned into the multi-clone site(MCS) of the eukaryotic expression vector pVAX1. The expressinig units of hIL-12 and siRNA were cloned into the BspH I and Mlu I site of pVAX1 respectively. Then the recombinant plasmid pVAX1-siHBV-HB-EGFP-hIL12 was transiently transfected HepG2 cells. The expression of HBV compound multi-epitope gene was observed through EGFP report gene. The expression of hIL-12 was analyzed by ELISA and the effects of anti-HBV siRNA was confirmed with rtPCR . Results: The analysis of enzyme digestion and sequencing both demonstrated that the trible-expressing HBV DNA vaccine has been constructed successfully. The green fluorescent image was detected in the transfected cells which could confirm the expression of the multi-epitope antigen gene. The amount of hIL-12 secretion was 1289pg/ml in supernatant at 48h after transfection and 1712pg/ml at 72h after transfection. The mRNA amount of HBV S gene, which was the siRNA target, had been obviously knockdown. Conclusion: The DNA vaccine co-expressing the HBV compound multi-epitope antigen gene, the hIL-12 and the siRNA genes was constructed and transiently expressed in HepG2 cells, and siRNA had shown us a good anti-HBV effect. It laid a foundation of further study on anti-HBV effect of the new DNA vaccine.

Objective To evaluate the application value of X-ray,echocardiogram,pulmonary perfusion scintigraphy,EBCT,Magnetic resonance Pulmonary angiography in diagnosis of PTE.Methods Twenty-five consecutive patients clinically diagnosed of having PTE were examined from july 2003 through March 2004. Patients underwent X-ray chest plain film, echoeardiogram, electronic beam computed tomographie (EBCT)angiography,ventilation-perfusion (V-P)seintigraphy,Magnetic resonance Pulmonary angiography (MRPA)and puhnonary angiography according to a strict diagnostic protocol.Two of the independent readers reviewed the pulmonary angiography and record all of the lobe and segmental involved in PTE and compared with other image method.Results Pulmonary angiography:all of the patients success underwent the technique,the pulmonary artery branch with PTE was in 556 of 775 branches (71.7%). Chest radiography had hints of diagnosis in 12 of 25 patients.Nine patients diagnosed with echocardiogram. Right heart enlargement was in 21,and pulmonary hypertension in 18.V-P scintigraphy revealed 247 segmental involved with PTE of 500 (52.0% ),and the sensitivity was 64.66% compare with the pulmonary angiography.There were 523 pulmonary branches involved PTE with EBCT pulmonary angiograpy of 775 branches,and the sensitivity was 94.06%.MRPA: 8 of 10 patients succeed in the technique, 155 branches of 248 were detected with PTE(62.5% ),the sensitivity was 81.29%.Conclusions EBCT is a high sensitivity method in diagnosis of PTE.Chest radiography and echocardiogram are the first-line modality of PTE.V-P scintigrapby is the valid compensation in diagnosis subsegmental pulmonary artery with PTE when EBCT miss diagnosis.Gd-CE-MRPA may be the second-line modality in diagnosis of PTE.

Objective To study the iodine nutritional status of population living in Tibetan pastoral areas,in order to provide a scientific basis for prevention and control of iodine deficiency disorders.Methods Drinking water samples were collected to test iodine content in agricultural town(Kajiaman) and pastoral area(Zuogaiduoma town) of Hezuo in Gannan Tibetan autonomous prefecture.Thirty of child-bearing age,pregnant and breastfeeding women were selected,respectively,and 90 male adults aged 20-50 from these families(1 from each family) and 90 children aged 8-10 (30 people in each age group) from local schools were randomly sampled at the same time,and urinary iodine (UI) was measured randomly.Edible salt and main food samples were collected to test iodine content from the 10 families of the three types of women,respectively,and they were asked to recall its family intake of food species in the past 24 h excluding spices.The water iodine was determined using arseniccerium redox method (GB/T 5750.1-2006) ; UI with ammonium persulfate digestion-arsenic cerium catalytic spectrophotometric method (WS/T 107-2006) ; salt iodine used direct determination method(GB/T 13025.7-1999); and food iodine with alkali the gray arsenic cerium contact colorimetry.All these work were done in May,2011.Results The average of water iodine was (1.63 ± 0.14)μg/L in agricultural areas and (2.08 ±1.90)μg/Lin pastoral areas of the 10 water samples tested,respectively.The median urinary iodine(MUI) among women of pregnant,lactating and child-bearing age,male adults and children was 141.99,126.65,253.33,258.07,191.0μg/L,respectively,in agricultural areas and 137.26,97.36,126.16,159.48,285.07 μg/L,respectively,in pastoral areas.The difference of MUI in lactating,male adults and children between pastoral and agricultural areas was statistically significant.The proportion of UI ＜ 50 μg/L was less than 20％,and ＜ 100 μg/L was less than 50％ among all population except lactating woman and pregnant women in pastoral areas.The iodized salt coverage rate was 100％(30/30) in agricultural areas and 90％(27/30) in pastoral areas,and the salt iodine was (32.1 ± 7.8)mg/kg in agricultural areas and (32.3 ± 6.0)mg/kg in pastoral areas,respectively.The food structure in agricultural areas was mainly potato,naked oat fruit,cabbage and so on,the average dietary iodine content was 285.7 μg/kg,and in pastoral areas was mainly chow mein,wheat flour,ghee,yogurt,barley and so on,the average dietary iodine content was 51.1 μg/kg.Conclusions There is no iodine deficiency in general in the population in Tibetan areas with low water iodine.However,iodine nutrition of pregnant women can not be guaranteed.It is recommended that classified guidance measures be taken to ensure the sustainable elimination of iodine deficiency disorders in the Tibetan minority areas.

A total of 101 patients undergoing operations for malignant gastrointestinal tumors (stage Ⅱ to Ⅲ) were enrolled and randomly assigned to receive intraperitoneal hyperthermal chemotherapy plus intravenous chemical injection (treatment group, n=51) or routine intravenous chemical injection (control group, n=50). Our results indicated that the recurrence rate and the metastatic rate in the treatment group were significantly lower than those in the control group (25.5% vs. 50.0%, 13.7% vs. 30.0%, both P< 0. 05), although the 3-and 5 year-survival rates were significantly higher (both P < 0. 05). Our data suggest that intraperitaneal hyperthermal chemotherapy plus general chemotherapy after surgery for malignant gastrointestinal tumors could effectively reduce tumor recurrence and metastases and improve long-term survival.