Current therapies for chronic hepatitis caused by hepatitis C virus (HCV) are limited . DNA vaccination may constitute a new immunotherapeutic strategy for various hepatitis virus infections by promoting specific cellular and humoral immunity. In this review we present the advances in choice of antigen gene, vaccine adjuvants and the methods of intracellular delivery, unresolved questions and therapeutic potential of HCV DNA vaccine.

Objective To study the influence of ENH Ⅰ of HBV on immune response of HBV DNA vaccine. Methods DNA fragments of HBsAg and HBsAg-ENH Ⅰ region of HBV, after being amplified by PCR using the complete genome DNA of HBV adr subtype, were inserted into VR1012 vectors. The recombinant plasmids were transfected into COS-7 cells and HepG2 cells, and injected into Balb/C mice. The expression of COS-7 cells, HepG2 cells and the cellular and humoral immune response of mice were determined with Western blot, ELISA and ELSPOT. Results HBsAg was expressed by transfected HepG2 cells and COS-7 cells. The quantity of expression by HepG2 cells increased apparently when transfected by that combined with ENH Ⅰ. In transfected COS-7 cells, there was no significant difference in the expression of HBsAg between those transfected by two recombinant plasmids. The HBsAb and the HBsAg specific CTL were found in mice in the second week after immunization, and there was no marked difference between those immunized by two recombinant plasmids. Conclusions When inserted into HBV DNA vaccine, ENH Ⅰ can promote the expression of HBsAg in transfected HepG2 cells, but can not affect the expression of transfected COS-7 cells and the immune response of immunized Balb/C mice.

Ergosterol is an economically important metabolite produced by yeast. To improve the production of ergosterol by Saccharomyces cerevisiae YEH56 (pHXA42) from molasses, a cheap and regenerative material, different strategies were applied. First, Plackett-Burman design and central composite design were applied to screen the significant factors in fermentation medium using ergosterol yield (g/L) as the response value. Ergosterol yield reached 371.56 mg/L by using the optimal fermentation medium in shake-flask culture (total sugar in molasses 40 g/L, KH2PO4 1 g/L, K2HPO4 1.86 g/L, CuSO4 x 5H2O 17.5 mg/L, FeSO4 x 7H2O 13.9 mg/L, MgSO4 x 5H2O 12.3 mg/L, corn steep liquor 10 mL/L), which was increased by 29.5% compared with the initial culture. Second, ergosterol yield was increased by 62.1% using a pH-control strategy in a 5-L bioreactor. Third, ergosterol production was improved further by using molasses feeding strategy. After 38 h fermentation, ergosterol yield reached 1 953.85 mg/L, which was 3.2 times of that in batch fermentation. Meanwhile, ergosterol production rate was increased by 42.7% compared with that in the batch culture.
Culture Media ; Ergosterol ; biosynthesis ; Fermentation ; Industrial Microbiology ; Molasses ; Saccharomyces cerevisiae ; genetics ; growth & development ; metabolism

BACKGROUND:Fetal congenital malformation is an important cause of perinatal fetal death,in which neural tube defects (NTDs) in prenatal deformity screening is more common.In recent years,with the deterioration of environment and the increase in the number of elderly maternal,patients with NTDs are increasing,bringing serious social and family economic burden.Therefore,modern imaging methods are used to provide theoretical basis for prenatal screening NTDs.OBJECTIVE:To study the development of fetal spinal cord morphology by means of imaging,so as to provide reference for the diagnosis of prenatal screening.METHODS:A computer-based retrieval of CNKI,WanFang,VIP,CBM and PubMed databases was conducted for the report on the development of fetal spinal cord from 1959 to 2017,and their different imaging studies were summarized.RESULTS AND CONCLUSION:In view of the impact of radiation on pregnant women and the fetus,in order to better imaging,for different organizational structures using different detection methods.(1) X-ray and CT:due to radiation damage to pregnant women and fetuses,they are only used for the cadaveric spine ossification center development,X-ray has been abandoned,and CT has not seen a live report.(2) Ultrasound is easy to operate,and non-invasive for pregnant women and fetuses,which is the preferred method of inspection.(3) MRI,as an important supplement means of ultrasound,can provide imaging basis for the prenatal assessment of fetal spinal cord development and diagnosis of related diseases.(4) Noticeably,harm of radiation to fetus should be considered.

Aim To observe histopathological changes of hippocampus after acute epilepsy induced by penty-lenetetrazole (PTZ)in rats.Methods Five groups as control group,PTZ-induced 24 hours(h)group,PTZ-induced 72 hours group,PTZ-induced 1 20 hours group and PTZ-induced 1 44 hours group were designed.PTZ (64 mg·kg -1 )was administered with a single intrap-eritoneal injection for generalized tonic-clonic sei-zures in the current experiment.Control and PTZ trea-ted animals were sacrificed after specific time points. Brain was dissected out and then evaluated for neuro-pathological changes using Nissl staining and immuno-histochemical technique.Results In this study PTZ-induced hippocampal neuron status apoptosis occurred at 24 hours and was sustained for 1 44 hours after status epilepticus.Whereas,activated caspase-3 and AIF ap-peared at 24 hours and were sustained for 1 44 hours af-ter status epilepticus.Conclusion The results of this study show that the significant histopathological chan-ges of hippocampus appear in the vicinity of 1 20 hours after intraperitoneal injection of pentylenetetrazole.

OBJECTIVE To invest igate the distribution of pathogenic bacteria and the antibiotic susceptibility of otitis media in plateau areaandto guide clinical drug application rationally. METHODS Middle ear secretions were collected from 218 inpatients and outpatients(220 ears) with otitis media in our department from December 2016 to January 2018 and were performed by isolation and identification of pathogenic bacteriaand drug sensitivity test. RESULTS 1. 152 strains of microbes were isolatedincluding 125 casesof bacterial infection and 8 cases of fungal infection. 2. The gram-positive bacteria in middle ear effusions of chronic suppurative otitis media was higher than those of cholesteatoma, of which Staphylococcus aureuswas the most frequently isolated pathogen. While Pseudomonas aeruginosa was the highest in cholesteatoma. 3. The antibiotic sensitivity of pathogenic bacteria varies from strain to strain. CONCLUSION Staphylococcus aureusand Pseudomonas aeruginosa were the main pathogenic bacteria. Common pathogenic bacteria were resistance to penicillin and levofloxacin, which were commonly used in clinic. Therefore, bacterial culture should be carried out and rational drug use should be guided.

Objective:To compare the efficacy and safety of unilateral biportal endoscopy (UBE) and microendoscopic discectomy (MED) in the treatment of lumbar spinal stenosis by Meta-analysis.Methods:PubMed, Web of Science, CNKI and Wanfang Data were searched from their establishment to January 2021 for all the studies on UBE and MED in the treatment of lumbar spinal stenosis. The data extracted were authors, year of publication, study design, subject characteristics, sample size, surgical protocol, age, sex ratio, duration of surgery, length of hospital stay, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI). The Meta-analysis was conducted with software Revman 5.3 to analyze the operation time, hospital stay, complication rate, waist and lower extremity VAS scores and ODI scores at preoperation, early postoperation and the last follow-up. The quality of the case-control studies included was evaluated using the Newcastle Ottawa Scale (NOS) while the methodological quality and risk of bias of the randomized controlled studies (RCT) included were evaluated using the Cochrane Bias Risk Assessment Tool.Results:Finally, 7 studies were included, 6 in English and one in Chinese. There were 2 RCTs and 5 case-control studies. There were 251 patients in the UBE group and 224 patients in the MED group. Compared with the MED group, the UBE group had a significantly shorter hospital stay ( MD=-2.28, 95% CI: -3.42 to -1.14, P<0.001), and a significantly lower VAS score for early postoperative low back pain ( MD=-0.80, 95% CI:-1.44 to -0.16, P=0.01). There were no significant differences between the 2 groups in operation time, complication rate, waist VAS scores at preoperation or the last follow-up, lower extremity VAS or ODI scores at preoperation, early postoperation or the last follow-up, or dural dilatation area ( P>0.05). Conclusions:In the treatment of lumbar spinal stenosis, compared with MED, UBE is superior in early relief of low back pain and hospital stay after operation, but shows no significant difference in long-term efficacy or safety.

Objective: This study was to analyze the association of lipid parameters with insulin resistance of Chinese elderly population in different glycemic status. Methods: Data were from China National Chronic Diseases and Nutrition Survey (2015). A total of 15 535 participants aged 60 and above who had completed survey questionnaire, physical examination, fasting blood biochemistry and insulin measurements were included in this study. According to the American Diabetes Association (2010) criteria, the participants were divided into normal glucose regulation, pre-diabetes, newly-diagnosed diabetes and previously-diagnosed diabetes. Multivariable logistic regression was preformed to assess the effects of lipid parameters on insulin resistance in different glycemic among the elderly population. Results: The proportion of normal glucose regulation, pre-diabetes, newly-diagnosed diabetes and previously-diagnosed diabetes was 50.46% (n=7 839), 22.19% (n=3 448), 12.46% (n=1 937) and 14.88% (n=2 311), respectively. The risk of insulin resistance increased with the elevated per quartile of triglycerides (TG) (OR=1.48,95%CI: 1.35-1.62), non-high-density lipoprotein cholesterol (Non-HDL)/HDL-C (OR=1.23, 95%CI: 1.12-1.35) and TG/HDL-C (OR=1.50, 95%CI: 1.36-1.65) and decreased with the elevated per quartile of HDL-C (OR=0.83, 95%CI: 0.76-0.90) after multivariate adjustment among normal glucose regulation participants. As for pre-diabetes participants, the risk of insulin resistance increased with the elevated per quartile of TG (OR=1.26, 95%CI: 1.14-1.39) and TG/HDL-C (OR=1.38, 95%CI: 1.24-1.54) and decreased with the elevated per quartile of HDL-C (OR=0.79, 95%CI: 0.71-0.87). The risk of insulin resistance increased with the elevated per quartiles of TG/HDL-C (OR=1.29, 95%CI: 1.12-1.48) among newly-diagnosed diabetes. As for previously-diagnosed diabetes, the risk of insulin resistance increased with the elevated per quartile of TG, Non-HDL/HDL-C and TG/HDL-C with adjusted OR(95%CI) about 1.28 (1.16-1.41), 1.37(1.21-1.55) and 1.51 (1.33-1.72) repsectivley and decreased with the elevated per quartile of HDL-C (OR=0.77, 95%CI: 0.67-0.87). Conclusion The relationship between lipid parameters and insulin resistance presented diversely in different glycemic status. The elderly with normal glucose regulation and previously-diagnosed diabetes should pay close attention to the change of TG/HDL-C, TG, HDL-C and Non-HDL/HDL-C. As for prediabetes participants, the TG/HDL-C, TG and HDL-C level change should be focused.

Objective:To investigate the effect of neoadjuvant chemotherapy on the safety of laparoscopic D 2 radical resection and prognosis of patients with locally advanced gastric cancer. Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 351 patients with locally advanced gastric cancer who underwent laparos-copic D 2 radical resection in the Second Affiliated Hospital of Air Force Medical University from December 2016 to December 2021 were collected. There were 256 males and 95 females, aged (58±9)years. Of the 351 patients, 124 cases undergoing neoadjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, 227 patients undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) effect evaluation of neoadjuvant chemotherapy; (3) intraoperative and postoperative situations; (4) postoperative histopathological examinations; (5) follow-up. Propensity score matching was done by the 1∶1 nearest neighbor matching method. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measure-ment data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curves, and the Log-Rank test was used for survival analysis. Results:(1) Propensity score matching conditions and comparison of general data of patients between the two groups of patients after matching. Of 351 patients, 154 cases were successfully matched, including 77 cases in the neoadjuvant chemotherapy group and 77 cases in the adjuvant chemotherapy group. The elimination of gender, age, preoperative body mass index, clinical T staging and clinical N staging confounding bias ensured comparability between the two groups after propensity score matching. (2) Effect evaluation of neoadjuvant chemotherapy. Of the 77 patients receiving neoadjuvant chemotherapy, none of patient achieved complete response, 26 patients achieved partial response, 46 patients showed stable disease, 5 patients had progression of disease, showing the objective response rate as 33.8%(26/77) and the disease control rate as 93.5%(72/77). There were 15 males and 11 females sensitive to neoadjuvant chemotherapy, while 46 males and 5 females not sensitive, showing a significant difference between them ( χ2=11.05, P<0.05). (3) Intra-operative and postoperative situations. The operation time, volume of intraoperative blood loss, cases with intraoperative blood transfusion, time to postoperative first flatus, time to postoperative first liquid food intake, duration of postoperative hospital stay, cases with postoperative immediate complications, cost of hospital stay were (308±71)minutes, 100(range, 20?600)mL, 5, 3.0(range, 2.0?10.0)days, 4.0(range, 2.0?12.0)days, 9.0(range, 4.0?31.0)days, 7, 7.96(7.37,8.58) ten thousand yuan in patients of the neoadjuvant chemotherapy group, versus (296±67)minutes, 100(range, 20?500)mL, 4, 3.5(range, 1.0?14.0)days, 4.0(range, 2.0?15.0)days, 8.0(range, 5.0?45.0)days, 11, 8.18(7.52,9.19) ten thousand yuan in patients of the adjuvant chemotherapy group, showing no signifi-cant difference in the above indicators between the two groups ( t=1.13, Z=?0.37, χ2=0.12, Z=?1.26, ?0.33, ?0.70, χ2=1.01, Z=?1.04, P>0.05). (4) Postoperative histopathological examinations. Results of postoperative histopatho-logical examinations showed that all 154 patients achieving R 0 resection. Cases with pathological T staging as stage T1, stage T2, stage T3, stage T4, cases with pathological N staging as stage N0, stage N1, stage N2, stage N3, number of positive lymph nodes, cases with human epidermal growth factor receptor 2 (negative, positive) were 3, 7, 5, 62, 27, 19, 19, 12, 1(range, 0?28), 59, 18 in patients of the neoadjuvant chemotherapy group, versus 0, 0, 2, 75, 17, 15, 21, 24, 3(range, 0?31), 44, 33 in patients of the adjuvant chemotherapy group, showing significant differences in the above indicators between the two groups ( Z=?3.39, ?2.55, ?3.12, χ2=6.60, P<0.05). (5) Follow-up. Of the 154 patients, 143 patients were followed up for 37(range, 5?69)months. The 3-year overall survival rate and 3-year disease-free survival rate was 72.1% and 70.0%, respectively, in patients of the neoadjuvant chemotherapy group, versus 74.8% and 76.6% in patients of the adjuvant chemo-therapy group, showing no significant difference in the above indicators between the two groups ( χ2=0.14, 0.60, P>0.05). Conclusions:Compared to postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not bring additional surgical risks, but can reduce the tumor stage of patients who underwent laparoscopic D 2 radical resection for locally advanced gastric cancer. However, it does not show any advantage in improving survival of patients.

Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.