Objective: To prepare an inactivated hepatitis A vaccine using a attenuated strain of hepatitis A virus (HAV) H2 and to analyze its immunizing dose, so as to provide the reference for development and production of inactivated hepatitis A vaccines. Methods: Human embryonic lung diploid cells (KMB17) were infected with attenuated HAV H2 strain to proliferate the virus, then the cells containing viruses were harvested, extracted and purified. The obtained virus concentrate was prepared into vaccine bulk and test vaccines with 1 280 EU/mL antigen content. Vaccine testing was carried out according to the inactivated hepatitis A vaccine standards specified in the Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). A total of 110 mice were randomly divided into 11 groups, including 5 dose groups (80, 160, 320, 640 and 1 280 EU/dose) of the test vaccine and the reference vaccine, as well as the adjuvant control group. Mice were immunized twice by intraperitoneal injection, their serum HAV antibodies were detected, and the geometric mean titer (GMT) and positive conversion rate of antibodies were analyzed to evaluate the immunising dose of the vaccine. Results: The antigen content and viral titer of the virus harvest solution were 5 120 EU/mL and 8.33 lgCCID50/mL, respectively. The removal rate of foreign protein reached 98.05% and the recovery rate of antigen was 66.25%. The test vaccine met the requirements of Part Ⅲ of the Pharmacopoeia of the People's Republic of China (2020 edition). The GMTs of HAV antibodies in the test vaccine and the reference vaccine dose groups after the second immunization were more than twice higher than those after the first immunization. Regardless of primary immunization or secondary immunization, the GMTs (log2) of HAV antibodies in the test vaccine groups with doses of 160 EU/dose and above were higher than those in the 80 EU/dose group (all P<0.05), while there was no statistically significant differences between the dose groups of 160 EU/dose and above (all P>0.05). The antibody positive conversion rate of 160 EU/dose and above of the test vaccine was 100.00% after the secondary immunization. Conclusions The inactivated hepatitis A vaccine of attenuated H2 strain tested in this study demonstrates strong immunogenicity in mice, suggesting its potential as a candidate vaccine. The preliminary analysis indicates an immunizing dose of 320 EU/dose for children and 640 EU/dose for adults.

Objective To investigate whether catalpol affects senile plaque formation and spatial learning and memory ability in the amyloid-β protein precursor/presenilin 1 (APP/PSI) double transgenic mice.Methods Three month-old APP/PS1 double transgenic mice were randomly divided into catalpoltreated and saline-treated groups (n =10),with C57 mice of the same age and genetic background as normal control group (n =10).The catalpol (in a dose of 5 mg · kg-1 · d-1) and the same amount of saline were peritoneally injected into Alzheimer' s disease (AD) model mice for 3 weeks.Immunohistochemical staining was performed to examine senile plaques in the brain of AD model mice,and Morris water maze was used to assess the spatial learning and memory abilities of the mice.Results Compared with the saline-treated AD model mice (6.0 ±0.6),the number of senile plaques of catalpol treated AD mice significantly decreased (2.3± 0.7; t =3.500,P =0.025); Mice in each groups had similar latency and path length to reach platform in visible platform test; In hidden platform test,catalpol-treated mice had a significant lesser latency and path length compared with saline-treated mice,furthermore,catalpol-treated mice had much more platform-crossing times (6.4 ± 0.8) than saline-treated mice (2.9 ± 0.4 ; t =5.592,P =0.001).Conclusion Catalpol can significantly decrease the senile plaque formation and improve the spatial learning and memory abilities of APP/PS1 double transgenic mice.

Objective To quantitate coronary tortuosity and provide favorable conditions for understanding the hemodynamic effects caused by coronary tortuosity.Methods We obtained all images from 72 patients who received coronary computed tomo-graphy scanning.After image post-processing,we extracted the medial axis of three main coronary vessel and analysed its coordi-nates on three dimensions.Then we calculated the tortuosity coefficient of coronary artery.Results Tortuosity coefficient was 6.66±7.54 in anterior descending,13.43±12.85 in left circumflex,and 1 7.61 ±7.67 in right coronary artery.We had proved its validity by the changes in morphology with simulated shapes.Conclusion We proposed a new method for quantitating coronary tor-tuosity,by computed tomography coronary imaging.The measurement results would not be affected by projection plane,vessel length or other artificial factors.

Objective:To compare the economic characteristics of the four artificial liver models [plasma exchange, half-dose plasma exchange combined with double plasma adsorption (DPMAS), pre-equal amount of plasma exchange followed by DPMAS, and pre-DPMAS followed by equal amount of plasma exchange] in the treatment of liver failure.Methods:A decision tree model was established with the Treeage pro 2011 software. The cost-effectiveness ratio and incremental cost-effectiveness value of four different treatment modalities were calculated and compared in patients with liver failure at early, mid and late stages, respectively. The sensitivity analysis of the model was performed using data from the preliminary research results of these groups.Results:The cost-effectiveness ratio and incremental cost-effectiveness value of patients treated with artificial liver therapy with half-dose plasma exchange combined with DPAMS plan in early stage liver failure were 89 547.79 and 34 665.34, which was lower than per capita GDP, so the increased cost had cost-effective advantages. In the middle and late stage of liver failure, the cost-effectiveness ratio and incremental cost-effectiveness value of pre-DPMAS followed by equal plasma exchange plan was 122 865.5 and 284 334.97, and 70 744.55 and 75 299.48, respectively, which was less than three times of per capita GDP. The increased cost was acceptable and had economic advantages. The sensitivity analysis results showed that the basic analysis results were reliable.Conclusion:Half-dose plasma exchange combined with DPAMS plan is the most cost-effective treatment for early liver failure, while pre-DPMAS followed by equal plasma exchange plan is the most economical treatment for mid and late stage liver failure.

Objective:This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies.Methods:A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed.Results:Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis ( r=0.547, P<0.001). Conclusions:The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

OBJECTIVE: To explore the genetic characteristics of idic(X)(p11.22) in Turner syndrome (TS). METHODS: Two fetuses suspected for sex chromosome abnormalities or ultrasound abnormalities were selected from Chengdu Women's and Children's Central Hospital in October 2020 and June 2020, and amniotic fluid samples were collected for G-banded chromosomal karyotyping analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH). RESULTS: The two fetuses were respectively found to have a karyotype of 45,X[47]/46,X,psu idic(X)(p11.2)[53] and 46,X,psu idic(X)(p11.2). CMA found that both had deletions in the Xp22.33p11.22 region and duplications in the p11.22q28 region. FISH showed that the centromeres in both fetuses had located on an isochromosome. CONCLUSION The combination of karyotyping analysis, FISH, and CMA is useful for the delineation of complex structural chromosomal aberrations. High-resolution CMA can accurately identify chromosomal breakpoints, which can provide a clue for elucidating the mechanism of chromosomal breakage and rearrangement.
Female ; Pregnancy ; Humans ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Sex Chromosome Aberrations ; Centromere ; Prenatal Diagnosis

Objective:To investigate the efficacy and diagnostic accuracy of changes in cytokine levels before and after non-biological artificial liver (referred to as ABL) treatment in patients with acute-on-chronic liver failure (ACLF) in order to establish a basis for treatment timing selection and short-term (28d) prognosis.Methods:90 cases diagnosed with ACLF were selected and divided into a group receiving artificial liver treatment (45 cases) and a group not receiving artificial liver treatment (45 cases). Age, gender, first routine blood test after admission, liver and kidney function, and procalcitonin (PCT) of the two groups were collected. The 28-day survival of the two groups was followed-up for survival analysis. The 45 cases who received artificial liver therapy were further divided into an improvement group and a deterioration group according to the clinical manifestations before discharge and the last laboratory examination results as the efficacy evaluation indicators. Routine blood test, coagulation function, liver and kidney function, PCT, alpha fetoprotein (AFP), β-defensin-1 (HBD-1), 12 cytokines and other indicators were analyzed and compared. A receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic efficacy of the short-term (28 d) prognosis and an independent risk factors affecting the prognosis of ACLF patients. According to different data, Kaplan-Meier method, log-rant test, t-test, Mann-Whitney U test, Wilcoxon rank-sum test, χ2 test, Spearman rank correlation analysis and logistic regression analysis were used for statistical analysis. Results:The 28-day survival rate was significantly higher in ACLF patients who received artificial liver therapy than that of those who did not receive artificial liver therapy (82.2% vs. 61.0%, P<0.05). The levels of serum HBD-1, alpha interferon (IFN-α) and interleukin-5 (IL-5) after artificial liver treatment were significantly lower in ACLF patients than those before treatment ( P<0.05), while liver and coagulation function were significantly improved compared with those before treatment ( P<0.05), and there was no statistically significant difference in other serological indexes before and after treatment ( P＞0.05). Before artificial liver treatment, serum HBD-1 and INF-α levels were significantly lower in the ACLF improvement group than in the deterioration group ( P<0.05) and were positively correlated with the patients' prognosis (deteriorating) ( r=0.591, 0.427, P<0.001, 0.008). The level of AFP was significantly higher in the improved ACLF group than that in the deterioration group ( P<0.05), and was negatively correlated with the prognosis (deteriorating) of the patients ( r=-0.557, P<0.001). Univariate logistic regression analysis showed that HBD-1, IFN-α and AFP were independent risk factors for the prognosis of ACLF patients ( P=0.001, 0.043, and 0.036, respectively), and that higher HBD-1 and IFN-α levels were associated with lower AFP level and a deteriorating prognosis. The area under the curve (AUC) of HBD-1, IFN-α, and AFP for short-term (28d) prognostic and diagnostic efficacy of ACLF patients was 0.883, 0.763, and 0.843, respectively, and the sensitivity and specificty was 0.75, 0.75, and 0.72, and 0.84, 0.80, and 0.83, respectively. The combination of HBD-1 and AFP had further improved the diagnostic efficiency of short-term prognosis of ACLF patients (AUC=0.960, sensitivity and specificity: 0.909 and 0.880 respectively). The combination of HBD-1+IFN-α+AFP had the highest diagnostic performance, with an AUC of 0.989, sensitivity of 0.900, and specificity of 0.947. Conclusion:Artificial liver therapy can effectively improve the clinical symptoms and liver and coagulation function of patients with ACLF; remove cytokines such as HBD-1, IFN-α, and IL-5 in patients with liver failure; delay or reverse the progression of the disease; and improve the survival rate of patients. HBD-1, IFN-α, and AFP are independent risk factors affecting the prognosis of ACLF patients, which can be used as biological indicators for evaluating the short-term prognosis of ACLF patients. The higher the level of HBD-1 and/or IFN-α, the higher the risk of disease deterioration. Therefore, artificial liver therapy should be started as soon as possible after the exclusion of infection. In diagnosing the prognosis of ACLF, HBD-1 has higher sensitivity and specificity than IFN-α and AFP, and its diagnostic efficiency is greatest when combined with IFN-α and AFP.

OBJECTIVE To evalu ate relat ed researches about the cost- benefit of pharmaceutical care in medical institutions with cost- benefit analysis，in order to provide evidence-based basis for related policy decisions and provide methodological reference for the cost- benefit evaluation of pharmaceutical care in the future. METHODS Retrieved from PubMed ，Embase，the Cochrane Library ，CBM，Wanfang database ，VIP and CNKI ，cost-benefit analysis was used to evaluate the researches about the cost-benefit of pharmaceutical care in medical institutions. Two researchers independently screened the research and extracted data according to the “Consolidated Health Economic Evaluation Reporting Standards Checklist ”. The quality of included studies was scored and evaluated systematically. RESULTS A total of 46 studies from 17 countries were included. Most of them came from the United States （21.74％），China（19.57％）and France （8.70％）. Average score of 46 literature was 14.30，of which 1 literature was excellent ，5 literature were good ，25 literature were qualified and 14 literature were unqualified. There were 25 research protocols of prospective study type ；the type of pharmaceutical care involved mostly was pharmaceutical monitoring （60.87％）， followed by prescription review （23.91％），medication reconciliation （8.70％）and outpatient pharmacy （6.52％）were less. The median cost-benefit ratio of pharmaceutical care was 5.05 （3.08，11.28）. CONCLUSIONS Pharmaceutical care shows good economic value ，and pharmacists have played an important role in saving medical resources ，but the design level and report quality of the existing studies need to be improved.

OBJECTIVE： To evaluate the clinical efficacy and economics of α-lipoic acid injection alone or combined with Mecobalamin injection versus Mecobalamin injection in the adjunctive treatment of diabetic peripheral neuropathy （DPN）. METHODS： Retrieved from PubMed， Cochrane Library， Embase， CNKI， VIP， CBM and Wanfang database， using “mecobalamin” “α-lipoic acid” and“diabetic peripheral neuropathy”as Chinese retrieval words， “Thioctic acid” “α-lipoic acid” “Methylcobal” “Mecobalamin” “Diabetic peripheral neuropathy” as English retrieval words， relevant randomized controlled trials （RCTs） were collected during the date of database establishment to Aug. 30th， 2018. Meta-analysis was conducted for total response rate. From the perspective of health care providers， cost-effectiveness analysis was used for economic evaluation and sensitivity analysis was conducted by a 15％ fluctuation of cost and total response rate. RESULTS： Totally 13 RCTs were included， involving 1 131 patients. The results of Meta-analysis showed that the total response rate of two-drug combination therapy in the treatment of DPN was higher than that of mecobalamin alone [RR＝1.41， 95％CI（1.28， 1.55）， P＜0.000 01]； that of α-lipoic acid injection alone in the treatment of DPN was higher than that of mecobalamin injection alone [RR＝1.35， 95％CI（1.25，1.47）， P＜0.000 01]， with statistical significance. Results of cost-effectiveness analysis showed that the cost-effectiveness ratio （CER） of Mecobalamin injection was 211.38 yuan， and CER of two-drug combination and α-lipoic acid injection alone were 1 484.42 and    1 383.49 yuan， respectively. The incremental cost-effectiveness ratio （ICER） were 4 589.52 and 4 638.82 yuan， which were all lower than per capita GDP in 2017. Sensitivity analysis showed that the cost-effectiveness analysis results kept stable. CONCLUSIONS： Compared with Mecobalamin injection， α-lipoic acid injection combined with Mecobalamin injection in the adjunctive treatment of DPN show high total response rate and economics.

Nonalcoholic steatohepatitis (NASH) has become the second leading cause of hepatitis and can further progress to liver fibrosis, liver cirrhosis, and even liver cancer; however, the detailed pathogenesis of NASH remains unclear, and there is still a lack of effective therapeutic drugs. MicroRNAs (miRNAs) are a class of non-coding, post-transcriptionally regulated, and highly conserved small RNAs in the body and play an important role in a variety of liver diseases. This article mainly reviews the role of miRNAs in the development and progression of NASH.