Reducing the mother-to-child transmission of hepatitis B virus(HBV)is crucial for achieving HBV elimination.Launched in July 2015 at the Great Hall of the People in Beijing,China,the"Zero Hepatitis B Mother-to-Child Transmission Project"(Shield Project)is a public welfare initiative integrating scientific prevention and applied research and aims to perform standardized management of pregnant women with hepatitis B using the mobile application of"Shield Project",in order to further reduce or eliminate the mother-to-child transmission of HBV.At present,the Shield Project has expanded nationwide,offering detailed implementation strategies,successful practices,and reliable data to support the global effort to eliminate the mother-to-child transmission of HBV.This article introduces the implementation strategies and outcomes of the Shield Project in four representative cases,in order to provide strong evidence for further understanding and preventing the mother-to-child transmission of HBV.

Stroke is one of the main diseases endangering the health and life of the middle-aged and elderly,and in recent years it shows a younger trend.It has the characteristics of high incidence,mortality and disability rate.Atherosclerosis is the main intervention target for stroke prevention and treatment.CircRNA is highly expressed in the cerebrovascular system and plays an important regulatory role in the pathogenesis of ischemia-reperfusion and ischemic stroke.This paper reviews the mechanism of circRNA and miRNA molecular network in the pathophysiological process of atherosclerosis,ischemic stroke and ischemia-reperfusion injury,so as to provide theoretical support for the application of circRNA in gene diagnosis and drug treatment of atherosclerotic ischemic stroke.

Objective To evaluate the application value of golden angle radial sparse parallel(Grasp)sequence in contrast-enhanced MRI of liver.Methods The imaging data of 30 patients who underwent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid contrast-enhanced MRI of liver were collected.With the same equipment,images were collected by Grasp sequence and breath-hold sequence separately,with an interval of less than 3 months.The subjective and objective scores of the late arterial phase and portal venous phase images were evaluated.Results There were no significant differences in all subjective scores of the late arterial phase and portal venous phase images between the two sequences(P＞0.05).The signal-to-noise ratio(SNR)of the late arterial phase images in the Grasp sequence was lower than that in the breath-hold sequence(148.4±52.8 vs 195.6±68.4),and the difference was statistically significant(P＜0.01).Although the SNR of the portal venous phase in the Grasp sequence was lower than that in the breath-hold sequence,the difference was not statistically significant(P＞0.05).There was no statistical difference in the other objective scores between the two sequences(P＞0.05).Conclusion The image quality of Grasp sequence in contrast-enhanced MRI of liver can meet the diagnositic requirements,and it is suitable for patients with poor breath-hold capacity,which has important application value.

【Objective】 To understand the status of COVID-19 vaccination among elderly adults in long-term care facilities and analyze the influencing factors so as to provide scientific basis for improving the policy of COVID-19 vaccination. 【Methods】 The socio-demographic characteristics, disease-related data, disability, and COVID-19 vaccination status of 575 elderly adults who resided in long-term care facilities in Shaanxi Province were collected via Sojumpin in January 2022. Factors that affected non-vaccinated elderly adults were analyzed by using the SPSS 25.0 software. 【Results】 Of the included 575 participants, 199 (34.6%) were not vaccinated against COVID-19. Univariate analysis showed that COVID-19 vaccination was associated with age, room type, length of stay, marital status, number of children, chronic diseases (i.e., diabetes, stroke, dementia), disability degree, and long-term medication use. Logistic regression analysis demonstrated that age of 90 years or above (OR=4.25), triple room (OR=6.17), moderate disability (OR=2.94), severe disability (OR=6.67), long-term medication use (OR=1.81), and stroke (OR=1.74) were independent risk factors for not injecting COVID-19 vaccine. 【Conclusion】 The COVID-19 vaccination coverage rate of elderly adults in long-term care facilities needs to be improved, and more attention should be paid to the high-risk groups (e.g., who are older, and have disability, long-term medication use, or stroke).

Objective:To learn about the levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in bone tissue of rats with different types of skeletal fluorosis and analyze their correlation.Methods:Thirty 4-week-old SPF grade healthy SD rats were selected. After adaptive feeding for 1 week, the rats were divided into control group (4 ml·kg -1·bw deionized water + standard maintenance diet), osteosclerosis group [20 mg·kg -1·bw sodium fluoride (NaF) + standard maintenance diet], and osteoporosis/osteomalacia group (20 mg·kg -1·bw NaF + low-calcium and low-protein partial diet) according to their body weight (100 - 120 g) by random number table method, with 10 rats in each group, half male and half female; gavaged 6 days each week and the experimental period was 5 months. At the end of the experiment, samples of rat heart blood and lower limb femur were collected. The contents of serum methyl donor S-adenosylmethionine (SAM) and its metabolite S-adenosylhomocysteine (SAH) in serum, and the levels of 5-mC and 5-hmC in bone tissue were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was used to determine the expression of DNA methyltransferase (DNMTs) and DNA hydroxymethylase (TETs) in bone tissue of rats. The correlation between serum SAM content, SAM/SAH ratio and bone tissue 5-mC level, and between the bone tissue 5-mC level and 5-hmC level was analyzed. Results:Serum SAM [11.03 (7.06, 18.63), 3.96 (2.32, 9.09), 3.91 (2.35, 4.46) nmol/L], SAH content [(4.69 ± 0.55), (5.41 ± 1.13), (13.90 ± 1.09) ng/L], SAM/SAH ratio [2.58 (1.54, 4.12), 0.62 (0.52, 1.69), 0.14 (0.13, 0.15)] and bone tissue 5-mC [103.39 (97.37, 109.35), 52.50 (50.19, 68.13), 55.03 (49.97, 59.57) ng/L], 5-hmC levels [(32.61 ± 8.84), (56.96 ± 8.48), (20.34 ± 6.22) ng/L] in the control group, osteosclerosis group and osteoporosis/osteomalacia group were compared, and the differences were statistically significant beween three groups ( H/ F = 12.81, 284.24, 21.85, 19.37, 55.23, P < 0.01). Compared with the control group, the content of SAM, the ratio of SAM/SAH, the level of 5-mC in the osteosclerosis group and osteoporosis/osteomalacia group, and the level of 5-hmC in the osteoporosis/osteomalacia group were lower ( P < 0.05), while the content of SAH in the osteoporosis/osteomalacia group and the level of 5-hmC in the osteosclerosis group were higher ( P < 0.05). Compared with the osteosclerosis group, the content of SAH in the osteoporosis/osteomalacia group was higher, while the ratio of SAM/SAH and the level of 5-hmC were lower ( P < 0.05). Western blot showed that there were statistically significant differences in the expression levels of DNMT1, DNMT3A, DNMT3B, TET1 and TET2 protein in bone tissue of rats in the control group, osteosclerosis group, and osteoporosis/osteomalacia group ( F = 285.45, 345.58, 239.83, 311.52, 318.24, P < 0.001). Among them, the expression levels of DNMT1, DNMT3A and DNMT3B protein in the osteosclerosis group and osteoporosis/osteomalacia group were lower than those in the control group, and the expression levels of DNMT1, DNMT3A and DNMT3B protein in the osteosclerosis/osteomalacia group were lower than those in the osteosclerosis group ( P < 0.05); the expression levels of TET1 and TET2 protein in osteosclerosis group were higher than those in the control group and osteoporosis/osteomalacia group, and the expression levels of TET1 and TET2 protein in the osteoporosis/osteomalacia group were lower than those in the control group ( P < 0.05). The results of Spearman rank correlation analysis showed that the content of SAM and the ratio of SAM/SAH in the control group, osteosclerosis group and osteoporosis/osteomalacia group were positively correlated with the level of 5-mC in bone tissue ( rs = 0.89, 0.92, 0.81, 0.73, 0.87, 0.73, P < 0.05). The levels of 5-mC and 5-hmC in bone tissue of rats in each group were negatively correlated ( rs = - 0.69, - 0.68, - 0.72, P < 0.05). Conclusions:The level of 5-mC in bone tissue of osteosclerotic fluorosis rats is low, and the level of 5-hmC is high, while those of osteoporosis/osteomalacia fluorosis rats are lower. The difference of 5-mC level in bone tissue of rats with different types of skeletal fluorosis is not significant, which may be related to the difference of 5-hmC level in bone tissue.

Objective:To investigate the combined effect of fluoride exposure and low nutrition on osteogenesis and osteoclastic differentiation in rats.Methods:SD rats were divided into four groups by the method of random number table, namely normal nutrition group, low nutrition treatment group, fluoride exposure group and co-treatment of fluoride and low nutrition group according to 2 × 2 factorial experimental design, 8 rats in each group, half male and half female. Five months after the experiment, immunohistochemistry was used to test the expression levels of femoral alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL). Analysis of variance of factorial design was used to determine the interaction between fluoride exposure and low nutrition on osteogenesis and osteoclastic differentiation.Results:The immunohistochemical results of bone tissue showed that there were significant differences in the expression levels of osteogenesis differentiation markers ALP and Runx2 between different groups ( F = 25.98, 17.77, P < 0.001). Compared with normal nutrition group (0.005 2 ± 0.002 7, 0.003 1 ± 0.001 4), the expression levels of ALP and Runx2 in fluoride exposure group were higher (0.019 5 ± 0.005 0, 0.014 4 ± 0.004 4, P < 0.05). There was no significant difference between low nutrition treatment group (0.002 6 ± 0.001 8, 0.004 4 ± 0.003 2) and co-treatment of fluoride and low nutrition group (0.003 6 ± 0.000 7, 0.002 9 ± 0.000 8, P > 0.05). The expression levels of ALP and Runx2 in co-treatment of fluoride and low nutrition group were lower than those of fluoride exposure group ( P < 0.05). There were significant differences in the expression level osteoclastic differentiation marker of RANKL and the ratio of RANKL/OPG ( F = 10.50, 31.05, P < 0.001). Among them, the RANKL/OPG ratio (0.115 3 ± 0.039 5) in fluoride exposure group was lower than that in normal nutrition group (1.426 3 ± 0.777 2), and the RANKL expression level and RANKL/OPG ratio (0.019 5 ± 0.007 7, 7.258 7 ± 3.674 3) in co-treatment of fluoride and low nutrition group were higher than those in normal nutrition group (0.004 4 ± 0.002 5, 1.426 3 ± 0.777 2, P < 0.05). However, there was no significant difference in the RANKL expression level and RANKL/OPG ratio (0.004 0 ± 0.001 9, 2.022 3 ± 0.753 7) in low nutrition treatment group ( P > 0.05). The expression level of RANKL and the ratio of RANKL/OPG in the co-treatment of fluoride and low nutrition group were higher than those in low nutrition treatment group and fluoride exposure group ( P < 0.05). The 2 × 2 analysis of variance of factorial design showed that fluoride exposure and low nutrition had interaction on ALP, Runx2, RANKL expression levels and RANKL/OPG ratio ( F = 4.38, 19.39, 22.12, 108.00, P < 0.05), antagonistic effect on ALP and Runx2 expression, synergistic effect on RANKL expression and RANKL/OPG ratio. Conclusions:In rat bone tissue, fluoride exposure promotes osteogenesis differentiation, inhibits osteoclastic differentiation dominated by active osteogenic function. The interaction between fluoride and low nutrition on osteogenesis and osteoclastic differentiation is antagonistic osteogenesis differentiation and synergistic promotion of osteoclastic differentiation. Normal nutrition conditions are material basis of osteogenesis differentiation, and low nutrition is the inducement of enhanced osteoclastic differentiation.

Objective:To establish a protein-protein interaction (PPI) network of 5 microRNA (miRNA) target genes differentially expressed in the plasma of coal-burning fluoride exposed population, and to screen genes and gene modules with important roles.Methods:Five miRNA (hsa-miRNA-3131, hsa-miRNA-4516, hsa-miRNA-6501-5p, hsa-miRNA-10b-5p, hsa-miRNA-4683) target genes differentially expressed in the plasma of coal-burning fluoride exposed population screened by our previous study were mapped to the STRING online database (https://string-db.org), and the PPI network was screened. The Cytoscape v3.6.0 software was used to visualize the PPI network, the topological attribute values degree and betweenness centrality were obtained by the NetworkAnalyzer plug-in, and the central node was filtered in the network (the node with the highest degree and the highest betweenness centrality). At the same time, the maximal clique centrality (MCC) analysis method in the CytoHubba plug-in was used to determine the important nodes in the PPI network. The cluster analysis was conducted by the MCODE plug-in, and the gene modules were screened in the PPI network. The protein names contained in the gene modules were submitted online to the KOBAS v3.0 database (http://kobas.cbi.pku.edu.cn/), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the gene modules selected by the MCODE plug-in.Results:The PPI network of target genes was consisted of 1 035 nodes and 4 346 edges. The degree (101) and betweenness centrality (0.010 723 89) of ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) were the highest, which was the central node of the PPI network. According to MCC analysis, UBA52 was an important node in the PPI network. The top 5 gene modules were selected from the PPI network, and the highly enriched gene pathways in the KEGG pathway enrichment analysis of the 5 gene modules included ubiquitin mediated proteolysis, spliceosome, endocytosis, neuroactive ligand-receptor interaction and vesicular transport.Conclusion:The PPI network of 5 miRNA target genes differentially expressed in the plasma of people exposed to coal-burning pollution of fluoride is successfully established, and the UBA52 gene and the 5 main pathways of gene modules are selected.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Objective:To evaluate the clinical efficacy of human-like collagen scar repair gel in the treatment of proliferative hypertrophic scar.Methods:The clinical effect of smear-like silicone ointment on patients with hypertrophic scars after prolonged injury or 4-6 months after surgery, the difference of curative effects between 3-18 years old juvenile group and 19-45 years old adult group, were analyzed by multicenter randomized controlled clinical study. Among them, 58 cases were treated with human-like collagen scar repair gel, 39 cases in adult group and 19 cases in minor group; 30 cases were using Silicone Gel, 20 cases in adult group and 10 cases in minor group. The differences in scar color, thickness, blood vessel distribution, softness, patient's self-conscious symptoms, clinical efficacy scores and adverse reactions were analyzed before and after application of the products at 4, 8, 12 and 24 weeks.Results:The scores of the two groups before treatment were slightly higher than those of the control group except the softness and thickness score test group ( P<0.05). There was no significant difference in the remaining parameters ( P>0.05). The efficacy scores at the 4th, 8th, 12th and the 24th week after application of the two groups showed that there were significant differences in the therapeutic indicators after treatment for different time ( P<0.05) and age grouping. There was no significant difference between juvenile group and adult group ( P>0.05). There was a statistically significant difference in the time points of different clinical evaluation scores ( P<0.05). There was no interaction between the evaluation time and the experimental control group and age group ( P>0.05); and not affected by group or age grouping ( P>0.05), no adverse reactions occurred in either group. Conclusions:Human-like collagen scar repair gel is safe and effective in the treatment of proliferative hypertrophic scar, and the clinical efficacy is not inferior to Silicone gel.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.