Objective To explore the prevention and treatment strategies for pancreatic fistula and pancreatic fistula combined with hemorrhage after pancreaticoduodenectomy.Methods We retrospectively reviewed 90 cases of pancreaticoduodenectomy at Guangdong Provincial People's Hospital from August 2019 to December 2022.According to whether postoperative pancreatic fistula occurred,the 90 patients were divided into a postoperative pancreatic fistula group(n=35)and a postoperative non-pancreatic fistula group(n=55).Among the 35 patients with postoperative pancreatic fistula,they were further categorized into two subgroups based on the presence of hemorrhage:the pancreatic fistula with hemorrhage group(n=10)and the pancreatic fistula without hemorrhage group(n=25).Chi-square test or Fisher's exact test was used for univariate analysis.Variables with statistical dif-ferences were selected for stepwise regression variable screening.Multivariate Logistic regression analysis was used to determine the independent risk factors for the occurrence of pancreatic fistula and postoperative pancreatic fistula with hemorrhage.Results All 90 patients successfully completed the pancreaticoduodenectomy.The incidence of postoperative pancreatic fistula was 38.9%(35/90).Significant differences were observed in pancreatic duct diam-eter(P=0.013),intraoperative blood loss(P=0.045),anastomosis type(P=0.045),and residual pancreatic texture(P=0.10)between the two groups(P<0.05).Multivariate logistic regression analysis revealed that soft pancreas texture,pancreatic duct diameter<3 mm,intraoperative blood loss≥300 mL,and pancreaticojejunostomy were independent risk factors for postoperative pancreatic fistula.Among patients with postoperative pancreatic fistula,multivariate logistic regression analysis identified pancreatic fistula volume>100 mL and duration of postop-erative pancreatic fistula>7 days as independent risk factors for hemorrhage.Conclusions The risk of pancreatic fistula after pancreatoduodenectomy is relatively high.Attention to preoperative pancreatic duct diameter and standardized evaluation of pancreatic texture can help identify postoperative pancreatic fistula.Careful hemostasis during operation and avoidance of early postoperative hemorrhage can reduce the incidence of grade B and C pan-creatic fistulas.Patients with pancreatic fistula should be warned of the occurrence of combined hemorrhage when the fistula volume is greater than 100ml and the duration of postoperative pancreatic fistula is greater than 7 days.

In recent years, the genome editing technologies based on the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) have developed rapidly. The system can use homologous directed recombination (HDR) to achieve precise editing that it medicated, but the efficiency is extremely low, which limits its application in agriculture and biomedical fields. As an emerging genome editing technology, the CRISPR/Cas-mediated DNA base editing technologies can achieve targeted mutations of bases without generating double-strand breaks, and has higher editing efficiency and specificity compared with CRISPR/Cas-mediated HDR editing. At present, cytidine base editors (CBEs) that can mutate C to T, adenine base editors (ABEs) that can mutate A to G, and prime editors (PEs) that enable arbitrary base conversion and precise insertion and deletion of small fragments, have been developed. In addition, glycosylase base editors (GBEs) capable of transitioning from C to G and double base editors capable of editing both A and C simultaneously, have been developed. This review summarizes the development, advances, advantages and limitations of several DNA base editors. The successful applications of DNA base editing technology in biomedicine and agriculture, together with the prospects for further optimization and selection of DNA base editors, are discussed.
Agriculture ; CRISPR-Cas Systems/genetics* ; DNA/genetics* ; Gene Editing ; Technology

Objective:To evaluate the persistence of HBsAg-specific antibodies eight years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to primary immunization.Methods:From August to September 2009, rural communities in Zhangqiu district of Ji'nan city were selected as the study site. The subject's inclusion criteria were 18 to 49 years old, local resident population, without HBV infection history and HepB vaccination history, and good health status. Antibodies against hepatitis B surface antigen (anti-HBs) were detected in adults following the standard primary vaccination. Those who were non-responders (anti-HBs titer <10 mIU/ml) were revaccinated with three doses of HepB and included in the study. Blood samples were collected from all of them at one month (T 1), two years, four years, and eight years after revaccination. The three indexes of anti-HBs, hepatitis B surface antigen (HBsAg), together with antibody against hepatitis B core antigen (anti-HBc), were measured by chemiluminescence microparticle immunoassay (CMIA). Results:The proportion of subjects with anti-HBs titers ≥10 mIU/ml was 85.12% (549/645) at T 1, 60.60% (283/467) at two years, 55.90% (199/356) at four years and 55.09% (222/403) at eight years after revaccination. The first two years' annual decline rates, three to four years and five to eight years, were 15.62%, 3.96%, and 0.36%. The GMC of anti-HBs was 153.92 mIU/ml at T 1, 21.43 mIU/ml at two years, 15.02 mIU/ml at four years, and 13.68 mIU/ml at eight years. In the first two years, three to four years and five to eight years, the annual decline rate of GMC was 62.69%,16.28%, and 2.31%, respectively. Multivariable analysis showed that the titer of anti-HBs at T 1 was independently associated with the persistence of anti-HBs at eight years after revaccination. Compared with anti-HBs titer <100 mIU/ml , those whose anti-HBs titers were 100-mIU/ml and ≥1 000 mIU/ml at T 1 had a higher positive rate of anti-HBs ( OR=14.13, P<0.001; OR= 62.91, P<0.001) and a higher probability of anti-HBs titer ( β=1.88, P<0.001; β=3.24, P<0.001) at 8 years after revaccination. Nobody was found seroconversion of HBsAg, and the anti-HBc positive rate was 14.14% (57/403). Conclusions:Following revaccination with three doses of HepB in adults who were non-responsive to primary immunization, anti-HBs titers declined rapidly within the first four years. They then maintained a stable level after the fifth year. More than half still kept anti-HBs protective titer at eight years after revaccination. The immunity persistence was associated with anti-HBs titer at one month after revaccination.

Objective To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization. Methods A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively. Results Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95%CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI:12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively. Conclusion The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.

Objective To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization. Methods A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low-responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively. Results Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95%CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI:12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti-HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was≥1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was ≤99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was≥1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively. Conclusion The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination.