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De-Yi Liu,1,* Yi-Nan Li,1,* Jia-Yi Wu,1,2 Zhen-Xin Zeng,1 Yang-Kai Fu,1 Han Li,1 Xiang-Ye Ou,1 Zhi-Bo Zhang,3 Shuang-Jia Wang,4 Jun-Yi Wu,1,2 Mao-Lin Yan1,2 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepato-Biliary-Pancreatic and Vascular Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217130 ; +86 591-88217140, Fax +86 591-87557768, Email 1248087863@qq.com; yanmaolin74@163.comPurpose: The prognosis of hepatocellular carcinoma (HCC) with extrahepatic metastases (EM) is poor. The efficacy and safety of transcatheter arterial chemoembolization combined with lenvatinib plus anti-programmed cell death 1 inhibitors (triple therapy) for HCC with EM remains unclear. In this study, we aimed to determine the efficacy and safety of triple therapy in HCC patients with EM.Patients and Methods: This study retrospectively reviewed HCC patients with EM who received triple therapy and analyzed their survival rate using the Kaplan–Meier method. Univariate prognostic analysis of each data point was performed using the Log rank test, and multivariate prognostic analysis was performed using the Cox proportional risk regression model.Results: Among 60 HCC patients with EM who underwent triple therapy, the most common sites of metastasis were as follows (in descending order): the lungs (n=27), lymph nodes (n=22), and bones (n=10). After triple therapy, the median progression-free survival and median overall survival were 6 and 18.63 months, respectively. The 6-month, 1-year, and 2-year cumulative survival rates were 87.7%, 68.6%, and 26.8%, respectively. In the multivariate analysis, neutrophil-to-lymphocyte ratio (NLR) ≥ 4 and alpha-fetoprotein (AFP) level ≥ 400 ng/mL were independently associated with overall survival.Conclusion: Our findings revealed that triple therapy is an effective, well-tolerated regimen for HCC patients with EM. AFP level and NLR are prognostic risk factors for triple therapy in this patient population.Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, lenvatinib, alpha-fetoprotein, neutrophil-to-lymphocyte ratio

Zhong-Tai Lin,1,2,* Shao-Ming Wei,1,3,* Jun-Yi Wu,1,3,* Zhi-Bo Zhang,4 Shuang-Jia Wang,5 Jian-Yin Zhou,6 Meng-Chao Luo,1,3 Zhen-Xin Zeng,1 Xiang-Ye Ou,1 Yang-Kai Fu,1 Han Li,1 De-Yi Liu,1 Jia-Yi Wu,1,3 Mao-Lin Yan1,3 1The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 5Department of Hepato-Biliary-Pancreatic and Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China; 6Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Yi Wu; Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 0591-88217140, Fax +86 0591-87557768, Email tyhjwjy@163.com; yanmaolin74@163.comBackground: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery.Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts.Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229– 1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119– 1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092– 0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079– 0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373– 4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147– 372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent.Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.Keywords: unresectable, hepatocellular carcinoma, conversion therapy, adjuvant therapy, recurrence-free survival, overall survival

Shu-Qun Li,1– 3,* Jun-Yi Wu,1,2,* Jia-Yi Wu,1,2,* Huang Xie,4,* Jin-Hai Li,1,2 Zhen-Xin Zeng,1,2 Yang-Kai Fu,1,2 De-Yi Liu,1,2 Han Li,1,2 Wei-Zhao Chen,1,2 Jing-Yao Huang,4 Mao-Lin Yan1,2 1Department of Hepatobiliary Pancreatic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, 450001, People’s Republic of China; 4Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Lin Yan; Jing-Yao Huang, Tel +86 591-88217130 ; +86 13705962563, Fax +86 591-87557768 ; +86 591-87113828, Email yanmaolin74@163.com; hjy999@126.comPurpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4).Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan–Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.Results: Median follow-up duration was 18 (4.0– 26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8– 30.5) months, whereas the median PFS was 14.5 (range, 1.3– 27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred.Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.Keywords: transarterial chemoembolization, lenvatinib, programmed death 1 inhibitor, hepatic cellular carcinoma, main trunk portal vein, triple therapy

Meng-Chao Luo,1,2,&ast; Jia-Yi Wu,1,3,&ast; Jun-Yi Wu,1,3 Zhong-Tai Lin,1,2 Yi-Nan Li,3 Zhen-Xin Zeng,3 Shao-Ming Wei,1,2 Mao-Lin Yan1,3 1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, 350001, People’s Republic of China; 2Department of General Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Lin Yan, The Shengli Clinical Medical College of Fujian Medical University, Dongjie Road 134, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88217130, Fax +86 591-87557768, Email yanmaolin74@163.com Shao-Ming Wei, Department of General Surgery, Fujian Provincial Hospital, Jinrong South Road 516, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86 591-88618707, Fax +86 591-88618900, Email 67468424@qq.comPurpose: Few reliable biomarkers for predicting the efficacy of triple therapy (lenvatinib + immune checkpoint inhibitors + transarterial chemoembolization) exist for patients with unresectable hepatocellular carcinoma (uHCC). This study explored the prognostic role of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) levels in patients with uHCC receiving triple therapy.Patients and Methods: This retrospective study included 93 patients with uHCC who received triple therapy at Fujian Provincial Hospital between August 2020 and November 2022. Depending on the respective baseline levels, the patients were divided into high-AFP and high-DCP groups. An early response was defined as an AFP or DCP concentration > 50% less than the baseline concentration after 6 weeks of triple therapy. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS).Results: After 6 weeks of triple therapy, 75.3% (58/77) and 78.9% (60/76) of patients in the high-AFP and high-DCP groups achieved an objective response. Early AFP and DCP responses were positively associated with ORR (high-AFP group: odds ratio [OR]: 13.542; 95% confidence interval [CI]: 3.991– 45.950, p< 0.001; high-DCP group: OR: 17.853; 95% CI: 4.478– 71.179, p< 0.001). In the high-AFP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the AFP responders than those in the non-responders (PFS: 66.4%, 59.6%, 48.2% vs 42.3%, 19.3%, 0%, p< 0.001; OS: 94.5%, 90.4%, 77.3% vs 75.6%, 66.2%, 49.6%, p=0.006). In the high-DCP group, the 6-month, 12-month, and 18-month PFS and OS rates were higher in the DCP responders than those in the non-responders (PFS: 67.4%, 57.7%, 39.0% vs 38.9%, 8.1%, 0%, p< 0.001; OS: 94.7%, 94.7%, 83.3% vs 77.0%, 53.9%, 36.0%, p< 0.001).Conclusion: After 6 weeks of triple therapy, an AFP or DCP reduction of > 50% predicts better treatment outcomes in uHCC patients.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, des-gamma-carboxyprothrombin, combination therapy, tumor response

Nitrogen has important effects on plant growth and defense. Although studies on the alternation in plant chemical defense by nitrogen fertilization have been extensively reported, how it affects physical defense is poorly understood. Two rice (Oryza sativa L.) (Poales: Poaceae) varieties (LDQ7 and YLY1) were applied with varying nitrogen regimes (0.90 and 180 kg ha-1) to study their physical defense against the brown planthopper (BPH) Nilaparvata lugens (Hemiptera: Delphacidae) in this study. Results of the electrical penetration graph showed that BPH searching and penetrating duration time was shortened with increasing nitrogen application. Also, the tubercle papicle of rice leaves decreased with increasing nitrogen application, while rice leaves' surface structure and waxy composition changed with increasing nitrogen application. In field experiments, BPH populations increased with the application of nitrogen fertilizer. These findings suggest that nitrogen input can affect plant-insect interactions by reducing the physical defense of plants, which provides new ideas for the organic combinations of yield increase and pest control in rice fields., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT)., Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts., Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively)., Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wei, Fu, Zeng, Huang, Lv, Chen, Wei, Zhang, Zhou, Wu and Yan.)

Conspiracy theories tend to be prevalent, particularly in societies with high economic inequality. However, few studies have examined the relationship between economic inequality and belief in conspiracy theories. We propose that economic inequality leads people to believe conspiracy theories about economically advantaged groups (i.e., upwards conspiracy theories) and that moral evaluations of those groups mediate this relationship. Study 1 (N = 300) found support for these ideas in a survey among Chinese residents. Study 2 (N = 160) manipulated participants' perceptions of economic inequality in a virtual society. The manipulation shaped moral evaluations of economically advantaged groups, and conspiracy beliefs, in the predicted manner. In Study 3 (N = 191) and Study 4 (N = 210), we experimentally manipulated participants' perceptions of economic inequality in real Chinese society and replicated the results of Study 2. In addition, in Study 4, we find that economic inequality predicts belief in conspiracy theories about economically disadvantaged groups (i.e., downward conspiracy theories), which was mediated by anomie. We conclude that perceived economic inequality predicts conspiracy theories about economically advantaged groups and that moral evaluations account for this effect. Also, upward and downward conspiracy theory beliefs are associated with different psychological processes., (© 2023 The Authors. British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background and Aims: Transcatheter arterial chemoembolization combined with lenvatinib and PD-1 inhibitors (triple therapy) exhibits promising efficacy for unresectable hepatocellular carcinoma (uHCC). We aimed to evaluate the prognosis of patients with uHCC who received triple therapy and develop a prognostic scoring model to identify patients who benefit the most from triple therapy., Methods: A total of 246 patients with uHCC who received triple therapy at eight centers were included and assigned to the training and validation cohorts. Prognosis was evaluated by the Kaplan-Meier curves. The prognostic model was developed by utilizing predictors of overall survival (OS), which were identified through the Cox proportional hazards model., Results: In the training cohort, the 3-year OS was 52.0%, with a corresponding progression-free survival (PFS) of 30.6%. The median PFS was 13.2 months [95% confidence interval, 9.7-16.7]. Three variables (total bilirubin ≥ 17 μmol/L, alpha-fetoprotein ≥ 400 ng/mL, and extrahepatic metastasis) were predictors of poor survival and were used for developing a prognostic model (TAE score). The 2-year OS rates in the favorable (0 points), intermediate (1 point), and dismal groups (2-3 points) were 96.9%, 61.4%, and 11.4%, respectively (p < 0.001). The PFS was also stratified according to the TAE score. These findings were confirmed in an external validation cohort., Conclusions: Triple therapy showed encouraging clinical outcomes, and the TAE score aids in identifying patients who would benefit the most from triple therapy., (© 2023. Asian Pacific Association for the Study of the Liver.)

Background: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy., Methods: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice. Cardiac-specific knockout of USP28 in the db/db background mice was generated by crossbreeding db/m and Myh6-Cre + /USP28 fl/fl mice. Recombinant adeno-associated virus serotype 9 carrying USP28 under cardiac troponin T promoter was injected into db/db mice. High glucose plus palmitic acid-incubated neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing, immunoprecipitation and mass spectrometry analysis, protein pull-down, chromatin immunoprecipitation sequencing, and chromatin immunoprecipitation assay., Results: Microarray profiling of the UPS (ubiquitin-proteasome system) on the basis of db/db mouse hearts and diabetic patients' hearts demonstrated that the diabetic ventricle presented a significant reduction in USP28 expression. Diabetic Myh6-Cre + /USP28 fl/fl mice exhibited more severe progressive cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared with their controls. On the other hand, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Adeno-associated virus serotype 9-USP28 diabetic mice also exhibited less lipid storage, reduced reactive oxygen species formation, and mitochondrial impairment in heart tissues than adeno-associated virus serotype 9-null diabetic mice. As a result, USP28 overexpression attenuated cardiac remodeling and dysfunction, lipid accumulation, and mitochondrial impairment in high-fat diet/streptozotocin-induced type 2 diabetes mice. These results were also confirmed in neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. RNA sequencing, immunoprecipitation and mass spectrometry analysis, chromatin immunoprecipitation assays, chromatin immunoprecipitation sequencing, and protein pull-down assay mechanistically revealed that USP28 directly interacted with PPARα (peroxisome proliferator-activated receptor α), deubiquitinating and stabilizing PPARα (Lys152) to promote Mfn2 (mitofusin 2) transcription, thereby impeding mitochondrial morphofunctional defects. However, such cardioprotective benefits of USP28 were largely abrogated in db/db mice with PPARα deletion and conditional loss-of-function of Mfn2., Conclusions: Our findings provide a USP28-modulated mitochondria homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts, suggesting that USP28 activation or adeno-associated virus therapy targeting USP28 represents a potential therapeutic strategy for diabetic cardiomyopathy., Competing Interests: Disclosures None.

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR)., Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells., Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 ( p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL ( p = 0.015) were independent predictors of MPR., Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied., Methods: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed., Results: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient., Conclusion: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects., (© 2024 S. Karger AG, Basel.)

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT., Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS)., Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS., Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Zeng, Wu, Li, Wang, Fu, Wu, Wei, Lv, Chen, Huang, Cheng and Yan.)

Carbon capture, utilization, and storage (CCUS) technology is widely recognized as a key solution for mitigating global climate change. Consequently, it has received significant attention from countries worldwide. However, carbon dioxide corrosion poses a significant challenge to CCUS and represents a bottleneck to the large-scale development and application of this technology. To mitigate this issue, this review starts with a discussion of corrosion problems in CCUS. Later, the fundamentals of the carbon dioxide corrosion mechanism are introduced. Then, the influences of various factors that affect the corrosion are highlighted, such as water content, pH, flow rate, etc. Afterward, we summarize the commonly used methods for corrosion protection, with a particular focus on inhibitor, given their eco-friendly and effective nature. Lastly, challenges and prospects are discussed to motivate future studies on developing novel, high-performance green inhibitor and studying the corresponding protection mechanisms, hoping to make some contributions to carbon emission reduction., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics., (© 2023. The Author(s).)

Background: Diabetic skin ulcers, a significant global healthcare burden, are mainly caused by the inhibition of cell proliferation and impaired angiogenesis. XB130 is an adaptor protein that regulates cell proliferation and migration. However, the role of XB130 in the development of diabetic skin ulcers remains unclear., Aim: To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose. Additionally, we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers, along with its molecular mechanisms., Methods: We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers. We investigated the effects of XB130 on wound healing using histological analyses. In addition, we used reverse transcription-quantitative polymerase chain reaction, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, immunofluorescence, wound healing, and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells (HUVECs) stimulated with high glucose. Finally, we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers., Results: RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers. Knockdown of XB130 promoted the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time. At the cellular level, knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs. Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130., Conclusion: The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs. Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway, which accelerates the healing of diabetic skin ulcers., Competing Interests: Conflict-of-interest statement: All the authors have declared no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: This retrospective study aimed to evaluate the safety and efficacy of cutting balloon angioplasty and conventional balloon angioplasty in supra-aortic arterial lesions caused by Takayasu arteritis., Methods: A total of 46 patients with supra-aortic arterial lesions between January 2011 and December 2018 were included. Cutting balloon angioplasty was applied for 17 patients with 24 supra-aortic arterial lesions (group A), while 29 patients with 36 supra-aortic arterial lesions received conventional balloon angioplasty (group B). The preoperative clinical manifestation, operation result, and postoperative outcomes were recorded and compared in the 2 groups., Results: Dizziness, visual disturbance, and unequal/absent pulses were the most common manifestations. The technical success of revascularization was 93.5% (43/46) in patients and 93.3% (56/60) in lesions. The stent implantation rate in group A was significantly lower than that in group B (4.2% vs. 50% in lesions, P < 0.05). Restenosis was the most common complication in both groups. Although the early (≤30 days) and late (>30 days) complications in group A were less than those in group B, there was no significant difference between the 2 groups (P > 0.05). Moreover, the primary-assisted patency of cutting balloon angioplasty and conventional balloon angioplasty at 1, 2, and 5 years were 66.7%, 62.5%, and 62.5% and 61.1%, 58.2%, and 49.8%, there was no significant difference between the 2 groups (P > 0.05), respectively., Conclusions: Compared with conventional balloon angioplasty, cutting balloon angioplasty could be considered a safe and effective alternative for supra-aortic arterial lesions caused by Takayasu arteritis, demonstrating better patency and clinical benefit., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The treatment of malignant tumors has entered the era of immunotherapy, and immune checkpoint inhibitors (ICIs) have brought significant benefits to patients. However, some patients are required to discontinue treatment with ICIs owing to factors such as disease progression and intolerable side effects. Faced with limited subsequent treatment options and complex medical needs, we searched PubMed, Embase, Cochrane library, and the NIH clinical trials database and found that ICI rechallenge could be a relevant clinical strategy. The factors that could affect the rechallenge efficacy include the patients' characteristics, therapeutic strategy selection, and the timing of treatment. Multiple factors are used to identify target population, of which clinical features and PD-L1 expression are more potential. Both single ICI rechallenge and combination therapy may have survival benefits. Patients who have tolerated initial immunotherapy well could undergo ICI rechallenge, while patients who have experienced grade 3 or higher immune-related adverse events should be carefully assessed prior to rechallenge. Interventions and the interval between two courses of ICI will clearly have an impact on the efficacy of subsequent treatment. Preliminary data evaluation supports further investigation on ICI rechallenge to identify the factors that could contribute to its efficacy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Atherosclerosis (As) is an inflammatory disease, and 2,3,4',5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) has been shown to suppress inflammation. However, it is still unclear if TSG alleviates As by inhibiting inflammation., Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the mRNA levels of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TNF-α and interleukin-6 (IL-6) in lipoprotein E knockout (ApoE -/-) mice with As. Hematoxylin-eosin (H&E) staining was performed to examine the atherosclerotic plaques in the aortic sinus. QRT-PCR and western blotting were used to measure the expression levels of TRAF6, TNF-α, and IL-6 in human umbilical vein endothelial cells (HUVECs), and enzyme-linked immunosorbent assays (ELISAs) were performed to monitor the levels of TNF-α and IL-6 in serum and cell culture medium., Results: TSG inhibited subendothelial plaques formation in the aortic sinus and inhibited the levels of total cholesterol (TCHO), low-density lipoprotein (LDL), TRAF6, TNF-α and IL-6 in AS mice in a dose-dependent manner. Moreover, TSG attenuated the oxidatively modified LDL (ox-LDL)-induced increases in TRAF6, TNF-α and IL-6 expression, whereas TRAF6 overexpression reversed the TSG-induced decreases in TRAF6, TNF-α, and IL-6 expression in HUVECs., Conclusions: TSG attenuates atherosclerotic progression by inhibiting inflammation via the downregulation of TRAF6 in ApoE-/- mice and HUVECs.

Objective: To compare the efficacies between open surgery and axillary non-inflatable endoscopic surgery in papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 343 patients with unilateral PTC treated by traditional open surgery (201 cases) and transaxillary non-inflating endoscopic surgery (142 cases) from May 2019 to December 2021 in the Head and Neck Surgery of Sichuan Cancer Hospital. Among them, 97 were males and 246 were females, aged 20-69 years. 1∶1 propensity score matching (PSM) was performed on the enrolled patients, and the basic characteristics, perioperative clinical outcomes, postoperative complications, postoperative quality of life (Thyroid Cancer-Specific Quality of Life), aesthetic satisfaction and other aspects of the two groups were compared after successful matching. SPSS 26.0 software was used for statistical analysis. Results: A total of 190 patients were enrolled after PSM, with 95 cases in open group and 95 cases in endoscopic group. Intraoperative blood losses for endoscopic and open groups were [20 (20) ml vs . 20 (10) ml, M (IQR), Z =-2.22], postoperative drainage volumes [170 (70)ml vs . 101 (55)ml, Z =-7.91], operative time [135 (35)min vs . 95 (35)min, Z =-7.34], hospitalization cost [(28 188.7±2 765.1)yuan vs . (25 643.5±2 610.7)yuan, x¯±s, t =0.73], postoperative hospitalization time [(3.1±0.9)days vs . (2.6±0.9)days, t =-3.24], and drainage tube placement time [(2.5±0.8) days vs . (2.0±1.0)days, t =-4.16], with statistically significant differrences (all P <0.05). There was no significant difference in surgical complications ( P >0.05). There were significant diffferences between two groups in the postoperative quality of life scores in neuromuscular, psychological, scar and cold sensation (all P <0.05), while there were no statistically significant differences in other quality of life scores (all P >0.05). In terms of aesthetic satisfaction 6 months after surgery, the endoscopic group was better than the open group, with statistically significant difference ( χ 2 =41.47, P <0.05). Conclusion: Endoscopic thyroidectomy by a gasless unilateral axillary approach is a safe and reliable surgical method, which has remarkable cosmetic effect and can improve the postoperative quality of life of patients compared with the traditional thyroidectomy.

Background: It is unclear whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be performed in hepatitis B virus-related hepatocellular carcinoma (HCC) patients with cirrhosis. We explored the efficacy of ALPPS in HCC patients., Methods: Data of 54 patients who underwent ALPPS between August 2014 and July 2020 at three centers were collected. Adverse factors affecting their prognosis were analyzed and subsequently compared with 184 patients who underwent transcatheter arterial chemoembolization (TACE)., Results: Overall survival rates of the ALPPS group at 1, 3, and 5 years were 70.6%, 38.4%, and 31.7%, respectively; corresponding disease-free survival rates were 50.5%, 22.4%, and 19.2%, respectively. The ALPPS group had a significantly greater long-term survival rate than the TACE group (before propensity score matching, P < 0.001; after propensity score matching, P = 0.002). Multivariate analysis demonstrated that multifocal lesions (P = 0.018) and macroscopic vascular invasion (P = 0.001) were prognostic factors for HCC patients who underwent ALPPS. After the propensity score matching, the multifocal lesions (P = 0.031), macroscopic vascular invasion (P = 0.003), and treatment type (ALPPS/TACE) (P = 0.026) were the factors adversely affecting the prognosis of HCC patients., Conclusion: ALPPS was feasible in hepatitis B virus-related HCC patients with cirrhosis and resulted in better survival than TACE., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC)., Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response., Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively., Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

The intracellular EscE protein tightly controls the secretion of the type III secretion system (T3SS) middle and late substrates in Edwardsiella piscicida. However, the regulation of secretion by EscE is incompletely understood. In this work, we reveal that EscE interacts with EsaH and EsaG. The crystal structures of the EscE-EsaH complex and EscE-EsaG-EsaH complex were resolved at resolutions of 1.4 Å and 1.8 Å, respectively. EscE and EsaH form a hydrophobic groove to engulf the C-terminal region of EsaG (56 to 73 amino acids [aa]), serving as the cochaperones of T3SS needle protein EsaG in E. piscicida . V61, K62, M64, and M65 of EsaG play a pivotal role in maintaining the conformation of the ternary complex of EscE-EsaG-EsaH, thereby maintaining the stability of EsaG. An in vivo experiment revealed that EscE and EsaH stabilize each other, and both of them stabilize EsaG. Meanwhile, either EscE or EsaH can be secreted through the T3SS. The secondary structure of EsaH lacks the fourth and fifth α helices presented in its homologs PscG, YscG, and AscG. Insertion of the α4 and α5 helices of PscG or swapping the N-terminal 25 aa of PscG with those of EsaH starkly decreases the protein level of the chimeric EsaH, resulting in instability of EsaG and deactivation of the T3SS. To the best of our knowledge, these data represent the first reported structure of the T3SS needle complex of pathogens from Enterobacteriaceae and the first evidence for the secretion of T3SS needle chaperones. IMPORTANCE Edwardsiella piscicida causes severe hemorrhagic septicemia in fish. Inactivation of the type III secretion system (T3SS) increases its 50% lethal dose (LD 50 ) by ~10 times. The secretion of T3SS middle and late substrates in E. piscicida is tightly controlled by the intracellular steady-state protein level of EscE, but the mechanism is incompletely understood. In this study, EscE was found to interact with and stabilize EsaH in E. piscicida . The EscE-EsaH complex is structurally analogous to T3SS needle chaperones. Further study revealed that EscE and EsaH form a hydrophobic groove to engulf the C-terminal region of EsaG, serving as the cochaperones stabilizing the T3SS needle protein EsaG. Interestingly, both EscE and EsaH are secreted. Our study reveals that the EscE-EsaH complex controls T3SS protein secretion by stabilizing EsaG, whose secretion in turn leads to the secretion of the middle and late T3SS substrates.

The regulatory role of cytokinins (CTKs) in leaf senescence has been documented in different species, including Chinese flowering cabbage. However, its physiological and molecular basis relatively remains unknown. In this study, exogenous application of a CTK analogue 6-benzylaminopurine (6-BA) significantly retarded leaf senescence of Chinese flowering cabbage, with less chlorophyll degradation and lower accumulation of reactive oxygen species (ROS) and malondialdehyde compared with the control group. Meanwhile, higher levels of soluble sugars and proteins, flavonoids, cellulose, amino acids, total phenols, procanthocyanins, and vitamin C were retained in 6-BA-treated leaves. 6-BA treatment also prevented the decline in endogenous CTK content and the increase in ethylene, abscisic acid, and jasmonic acid contents. Moreover, the comparative transcriptome analysis revealed that a total of 21,895 differently expressed genes (DEGs) were identified from four comparisons of 6-BA treatment versus the control during senescence. Further analysis showed that most of the identified DEGs were enriched in ROS, respiratory metabolism, and phytohormone pathways, and a total of 50 classes of transcription factors that were possibly involved in modulating these DEGs were obtained. The transcriptional levels of 18 DEGs were verified by Quantitative real-time PCR (qRT-PCR), which confirmed the accuracy of the transcriptomic data. Overall, these findings and data provide a comprehensive view of physiological and molecular events concerning with the CTK-mediated leaf senescence and -maintained quality in economical leafy vegetables., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The existing problems in the outcomes of randomized controlled trials (RCTs) of acupuncture for vascular cognitive impairment (VCI) during recent five years are analyzed and suggestions are proposed. The RCTs of acupuncture for VCI were selected in PubMed, EMbase, Cochrane Library, Clinical Trials, CNKI database, Wanfang database, VIP database, SinoMed database and Chinese Clinical Trial Registry (ChiCTR) from January 1, 2015 to September 14, 2020. The outcomes were extracted and analyzed. As a result, 21 RCTs were included and the outcomes used were divided into 9 categories: clinical symptom/sign indexes, quality of life indexes, neuroimaging indexes, neuroelectrophysiology indexes, blood biochemical indexes, hemorheology indexes, TCM syndrome score indexes, clinical efficacy indexes, and safety indexes. Among them, the top three of the most used outcomes were clinical symptoms/signs indexes (21, 100.0%), clinical efficacy indexes (14, 66.7%) and quality of life indexes (12, 57.1%). In the RCTs of acupuncture for VCI, attention should be paid to distinguish the primary outcomes and secondary outcomes, adopt objective and standardized efficacy evaluation, and give consideration to report the outcomes of safety, health economic and TCM characteristic indexes.

Objective: To analyze the current status of clinical trial registration of Traditional Chinese Medicine (TCM) for the treatment of neurological diseases., Methods: Interventional clinical trials of TCM treatment for ischemic stroke, hemorrhagic stroke, vascular cognitive impairment, tension-type headache before September 22, 2020 on the platform of Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov were searched. Two researchers independently selected the literature and extracted data., Results: A total of 180 interventional clinical trials were included for analysis. Out of 180 trials, 127 were from ChiCTR and 53 from ClinicalTrials.gov. The countries primary sponsoring the included trials were China (176, 97.8%), and the common categories of primary sponsors were hospital (131, 72.8%). Among the study design, the largest proportion of allocation was randomized (172, 95.6%), interventional model assignment was parallel (163, 90.6%), masking was double blind 49 (27.2%), and the sample size was ≤ 400 (144, 80.0%). The trials were most carried out at a single center (102, 56.7%). Among the included studies, 112 (62.2%) registered on ChiCTR attached the ethical approval documents. In terms of trial stages, 50 (27.7%) studies were in phase IV. The mostly used intervention was Chinese herbal medicines (99, 55%), acupuncture (68, 37.8%) was the second. By searching the registration number on China National Knowledge Infrastructure Database and PubMed, 38 (21.1%) registered trials were published, including 25 protocol studies and 14 research results with one (NCT02275949) published both the protocol and the results., Conclusions: Irregular and inadequate reporting, untimely update and publication, insufficient information on traditional medicine unique characteristics, and lack of international collaborations are the problems existing in the interventional clinical registration trials of traditional medicine treatment on neurological diseases. More efforts need to be made from the above aspects to standardize and improve the registration of traditional medicine trials.

Objective: To overview the methodological quality, report quality and evidence quality of the systematic review (SR) of acupuncture for vascular cognitive impairment ( VCI )., Methods: The SRs regarding acupuncture for VCI were searched in PubMed, Cochrane Library, EMbase, CNKI, SinoMed, Wanfang and VIP databases. The retrieval period was from the establishment of the database to September 24, 2020. The report quality, methodological quality and evidence quality of the included SRs were evaluated by PRISMA statement, the AMSTAR 2 tool and the GRADE system., Results: A total of 22 SRs were included, including 102 outcome indexes. The methodological quality was generally low, with low scores on items 2, 5, 7, 10, 14, 15 and 16. The report quality was good, with scores ranging from 19 points to 24.5 points. The problems of report quality were mainly reflected in the aspects of structural abstract, program and registration, other analysis and funding sources. The level of outcome indexes of SRs was mostly low or very low, and the main leading factor was limitation, followed by inconsistency and inaccuracy., Conclusion: Acupuncture for VCI is supported by low quality evidence of evidence-based medicine, but the methodological quality and evidence body quality of relevant SRs are poor, and the standardization is needed to be improved.