Transcriptional regulation based on transcription factors is an effective regulatory method widely used in microbial cell factories. Currently, few naturally transcriptional regulatory elements have been discovered from Saccharomyces cerevisiae and applied. Moreover, the discovered elements cannot meet the demand for specific metabolic regulation of exogenous compounds due to the high background expression or narrow dynamic ranges. There are abundant transcriptional regulatory elements in plants. However, the sequences and functions of most elements have not been fully characterized and optimized. Particularly, the applications of these elements in microbial cell factories are still in the infancy stage. In this study, natural regulatory elements from Medicago truncatula were selected, including the transcription factors MtTASR2 and MtTASR3, along with their associated promoter P_roHMGR1, for functional characterization and engineering modification. We constructed an inducible transcriptional regulation tool and applied it in the regulation of heterologous β-carotene synthesis in S. cerevisiae, which increased the β-carotene production by 7.31 folds compared with the original strain. This study demonstrates that plant-derived transcriptional regulatory elements can be used to regulate the expression of multiple genes in S. cerevisiae, providing new strategies and ideas for the specific regulation and application of these elements in microbial cell factories.
Medicago truncatula/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Transcription Factors/genetics* ; beta Carotene/biosynthesis* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Metabolic Engineering/methods* ; Regulatory Elements, Transcriptional/genetics* ; Plant Proteins/genetics*

Objective To investigate the clinical features of patients with China Liver Cancer Staging(CNLC)stage Ⅲhepatocellular carcinoma(HCC)achieving five-year sustained complete remission(CR)after local treatment combined with systemic therapy,as well as potential contributing factors,and to provide a reference for optimizing the treatment of advanced HCC.Methods A retrospective analysis was performed for the clinical data of six patients with CNLC stage Ⅲ HCC who were treated in Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2016 to December 2019 and achieved five-year sustained CR.Baseline characteristics,treatment modalities,and follow-up data were summarized,and a literature review was performed.Results The six patients had a mean age of 58.3±10.1 years,among whom five had stage Ⅲa HCC and one had stage Ⅲb HCC,and all patients had a history of hepatitis.The mean preoperative MELD score was 8.2±0.8 for the six patients,and there were five patients with Child-Pugh class A liver function and one with Child-Pugh class B liver function.All patients underwent transcatheter arterial chemoembolization,followed by sequential targeted drug therapy after surgery,with sorafenib for four patients and lenvatinib for two patients.Four patients with main portal vein tumor thrombus also received 125I seed implantation,one patient with the single-nodule type underwent radiofrequency ablation,and three patients received immunotherapy with camrelizumab.The median time to AFP normalization was 6 months,the median time from treatment to CR was 5.5 months,and the median follow-up time was 63 months.Conclusion Good liver function at baseline,an early and rapid reduction in AFP,and the combination of local treatment and systemic therapy are key factors for achieving long-term CR in patients with advanced HCC.Multi-center large-scale studies are needed in the future to further explore prognostic factors and optimize treatment regimens.

Objective To investigate the DSA imaging characteristics and efficacy of interventional treatment for post-pancreaticoduodenectomy hemorrhage(PPH),and to analyze the factors influencing recurrent bleeding following successful interventional hemostasis.Methods Clinical data of patients who underwent interventional treatment for PPH between January 2013 and December 2022 were retrospectively analyzed.All patients underwent DSA examination,and interventional therapy was the primary treatment option for patients with positive findings.Statistical analysis was performed on DSA angiography manifestations,bleeding sites,success rate of interventional treatment and hemostasis effectiveness.Univariate and multivariate logistic regression analysis were used to analyze the independent risk factors for rebleeding after interventional treatment for PPH.Results A total of 139 patients with PPH were included in this study.All 139 patients underwent DSA examination,with a positive rate of 82.01％(114/139)in the first examination.Major angiographic manifestations included contrast agent extravasation,pseudoaneurysm,and disrupted vascular architecture;bleeding sites included gastroduodenal artery in 45 cases(39.47％),hepatic artery in 22 cases(19.30％),and superior mesenteric artery in 32 cases(28.07％).107 patients underwent interventional treatment(81 embolization and 26 stenting),with a success rate of 91.59％(98/107).The independent risk factors for recurrent bleeding after interventional treatment in patients with PPH included preoperative bleeding(P＜0.001)and pancreatic fistula(P=0.041).Conclusion Interventional procedures for PPH can be efficient in diagnosis and treatment,with a high success rate and effective hemostasis.However,it should be noted that some patients remain at risk of recurrent bleeding after successful interventional hemostasis.

Objective:To apply patent metrics to analyze the distribution, development trends, and characteristics of patents related to orthokeratology lenses for assisted wearing, providing a reference for the research and development of such patents.Methods:Patents related to orthokeratology lenses for assisted wearing were retrieved by computer from the China National Intellectual Property Administration database, incopat, Derwent Innovations Index, Free Patents Online, Organisation Africaine de la Propriété Intellectuelle, and IP Australia. The search timeframe was from the establishing of these databases until March 8, 2024. Patent metrics methods, word frequency analysis, and high-frequency word co-occurrence analysis were used for data analysis.Results:A total of 60 relevant patents were selected. The development of orthokeratology lens-assisted wearing patents began relatively late but has shown a strong growth trend, reaching a peak around 2015. Chinese patents accounted for the largest share (91.7%, 55/60) , with Zhejiang Province, Beijing City, Jiangsu Province, Guangdong Province, and Shanghai City having the highest number of patents. The majority of the applicants were enterprises. The research focus in this field is on mechanical assistance patents for lens wearing, with cutting-edge technologies focusing on monitoring the displacement of lenses relative to the pupil and providing timely feedback and guidance.Conclusions:This study, using patent metrics, word frequency analysis, and high-frequency word co-occurrence analysis, provides a reference for patent applications and product development in orthokeratology lens-assisted wearing in nursing.

Objective To investigate the clinical features of patients with China Liver Cancer Staging(CNLC)stage Ⅲhepatocellular carcinoma(HCC)achieving five-year sustained complete remission(CR)after local treatment combined with systemic therapy,as well as potential contributing factors,and to provide a reference for optimizing the treatment of advanced HCC.Methods A retrospective analysis was performed for the clinical data of six patients with CNLC stage Ⅲ HCC who were treated in Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2016 to December 2019 and achieved five-year sustained CR.Baseline characteristics,treatment modalities,and follow-up data were summarized,and a literature review was performed.Results The six patients had a mean age of 58.3±10.1 years,among whom five had stage Ⅲa HCC and one had stage Ⅲb HCC,and all patients had a history of hepatitis.The mean preoperative MELD score was 8.2±0.8 for the six patients,and there were five patients with Child-Pugh class A liver function and one with Child-Pugh class B liver function.All patients underwent transcatheter arterial chemoembolization,followed by sequential targeted drug therapy after surgery,with sorafenib for four patients and lenvatinib for two patients.Four patients with main portal vein tumor thrombus also received 125I seed implantation,one patient with the single-nodule type underwent radiofrequency ablation,and three patients received immunotherapy with camrelizumab.The median time to AFP normalization was 6 months,the median time from treatment to CR was 5.5 months,and the median follow-up time was 63 months.Conclusion Good liver function at baseline,an early and rapid reduction in AFP,and the combination of local treatment and systemic therapy are key factors for achieving long-term CR in patients with advanced HCC.Multi-center large-scale studies are needed in the future to further explore prognostic factors and optimize treatment regimens.

Objective To systematically review the influencing factors of postoperative delirium in liver transplant recipients,providing a basis for future clinical intervention studies.Methods Literature were searched on the influencing factors of postoperative delirium in liver transplant recipients published in the China Biology Medicine disc(CBM),Wanfang Data,China National Knowledge Infrastructure(CNKI),VIP Information,PubMed,Cochrane Library,CINAHL,Web of Science and EMBASE databases from their inception to February 28,2025.The influencing factors of postoperative delirium were extracted and analyzed in liver transplant recipients.Results A total of 12 articles were included.The influencing factors of postoperative delirium in liver transplant recipients included patient factors(body mass index,history of preoperative alcohol abuse,history of infection within 2 months before surgery,preoperative hepatic encephalopathy,proportion of preoperative macrovesicular steatosis,preoperative model for end-stage liver disease score,acute physiology and chronic health evaluation II score,preoperative blood ammonia,preoperative total bilirubin,preoperative serum creatinine),surgical factors(long anhepatic period during surgery),treatment factors(perioperative medication use,prolonged intubation time,use of donation after cardiac death grafts),and postoperative related factors(elevated postoperative aspartate aminotransferase,postoperative sepsis,use of postoperative immunosuppressive drugs).Conclusions Postoperative delirium in liver transplant recipients is influenced by multiple factors.A multidimensional assessment and preventive strategy are required.Future research need focus on dynamic monitoring and personalized intervention plans of postoperative delirium.

Objective To systematically review the influencing factors of postoperative delirium in liver transplant recipients,providing a basis for future clinical intervention studies.Methods Literature were searched on the influencing factors of postoperative delirium in liver transplant recipients published in the China Biology Medicine disc(CBM),Wanfang Data,China National Knowledge Infrastructure(CNKI),VIP Information,PubMed,Cochrane Library,CINAHL,Web of Science and EMBASE databases from their inception to February 28,2025.The influencing factors of postoperative delirium were extracted and analyzed in liver transplant recipients.Results A total of 12 articles were included.The influencing factors of postoperative delirium in liver transplant recipients included patient factors(body mass index,history of preoperative alcohol abuse,history of infection within 2 months before surgery,preoperative hepatic encephalopathy,proportion of preoperative macrovesicular steatosis,preoperative model for end-stage liver disease score,acute physiology and chronic health evaluation II score,preoperative blood ammonia,preoperative total bilirubin,preoperative serum creatinine),surgical factors(long anhepatic period during surgery),treatment factors(perioperative medication use,prolonged intubation time,use of donation after cardiac death grafts),and postoperative related factors(elevated postoperative aspartate aminotransferase,postoperative sepsis,use of postoperative immunosuppressive drugs).Conclusions Postoperative delirium in liver transplant recipients is influenced by multiple factors.A multidimensional assessment and preventive strategy are required.Future research need focus on dynamic monitoring and personalized intervention plans of postoperative delirium.

Objective:To apply patent metrics to analyze the distribution, development trends, and characteristics of patents related to orthokeratology lenses for assisted wearing, providing a reference for the research and development of such patents.Methods:Patents related to orthokeratology lenses for assisted wearing were retrieved by computer from the China National Intellectual Property Administration database, incopat, Derwent Innovations Index, Free Patents Online, Organisation Africaine de la Propriété Intellectuelle, and IP Australia. The search timeframe was from the establishing of these databases until March 8, 2024. Patent metrics methods, word frequency analysis, and high-frequency word co-occurrence analysis were used for data analysis.Results:A total of 60 relevant patents were selected. The development of orthokeratology lens-assisted wearing patents began relatively late but has shown a strong growth trend, reaching a peak around 2015. Chinese patents accounted for the largest share (91.7%, 55/60) , with Zhejiang Province, Beijing City, Jiangsu Province, Guangdong Province, and Shanghai City having the highest number of patents. The majority of the applicants were enterprises. The research focus in this field is on mechanical assistance patents for lens wearing, with cutting-edge technologies focusing on monitoring the displacement of lenses relative to the pupil and providing timely feedback and guidance.Conclusions:This study, using patent metrics, word frequency analysis, and high-frequency word co-occurrence analysis, provides a reference for patent applications and product development in orthokeratology lens-assisted wearing in nursing.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

In recent years, with the development of organ preservation, surgical techniques, perioperative management and immunosuppression regimens, the success rate of liver transplantation and survival rate of the recipients have been significantly enhanced. Liver transplantation has become the optimal treatment for patients with end-stage liver disease. However, biliary complications still commonly occur after liver transplantation, especially biliary anastomotic stricture. Severe biliary anastomotic stricture will not only increase the cost of treatment, but also lead to graft loss and even affect the survival rate of recipients. Therefore, timely diagnosis and treatment of biliary anastomotic stricture play a significant role in improving the survival rate of liver transplant recipients. In this article, the risk factors, clinical symptoms, diagnosis and treatment of biliary anastomotic stricture after liver transplantation were reviewed, aiming to provide novel ideas for the research, diagnosis and treatment of biliary anastomotic stricture after liver transplantation, and further enhance clinical efficacy of liver transplantation and the quality of life of recipients.