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Qingqing Li,1,* Tong Su,2,* Xu Zhang,3,* Yanfeng Pan,1,* Shengli Ma,4 Lu Zhang,4 Xianqiang Zhang,1 Xiaojuan Gao1 1Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou city, People’s Republic of China; 2Department of Medical, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou city, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou city, People’s Republic of China; 4Department of Infectious Diseases, The People’s Hospital of Yongcheng, Yongcheng city, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanfeng Pan, Department of Infectious Diseases, the First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Jinshui District, Zhengzhou city, 450000, People’s Republic of China, Tel +8613938448759, Email panfirstfeng@163.comPurpose: To observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment.Patients and Methods: Data from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety.Results: Among the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88– 8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥ 3 AEs was 38.7%.Conclusion: Anlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.Keywords: hepatocellular carcinoma, anlotinib, sequential therapy, real world

Distributed learning is a very effective divide-and-conquer strategy for dealing with big data. As distributed learning algorithms become more and more mature, network security issues including the risk of privacy disclosure of personal sensitive data, have attracted high attention and vigilance. Differentially private is an important method that maximizes the accuracy of a data query while minimizing the chance of identifying its records when querying from the given data. The known differentially private distributed learning algorithms are based on variable perturbation, but the variable perturbation method may be non-convergence and the experimental results usually have large deviations. Therefore, in this paper, we consider differentially private distributed learning algorithm based on objective function perturbation. We first propose a new distributed logistic regression algorithm based on objective function perturbation (DLR-OFP). We prove that the proposed DLR-OFP satisfies differentially private, and obtain its fast convergence rate by introducing a new acceleration factor for the gradient descent method. The numerical experiments based on benchmark data show that the proposed DLR-OFP algorithm has fast convergence rate and better privacy protection ability.

Background: Hepatocellular carcinoma (HCC) is one of most common cancers with a high mortality rate. HBV/HCV infection is an important risk factor to trigger HCC. Therefore, developing serum biomarkers for early diagnosis is crucial to prolong survival in HCC patients. Methods: An antibody array technology was utilized to detect serum from 20 HBV-related HCC patients, 20 chronic hepatitis B patients and 20 normal population, whose results were further validated by ELISA. Results: Both antibody array and ELISA showed that ten growth factors (SCF R, GDF-15, HGF, FGF-4, IGFBP-1, PIGF, GH, GDNF, BDNF and IGF-1) were significantly differential in HCC patients when compared to the non-HCC population. Among these growth factors, the levels of SCF R, GDF-15, HGF, GH and IGF-1 showed significant correlation with hepatitis B and its severity, indicating that these growth factors may promote HCC progression by an HBV-specific mechanism. A therapy targeting these growth factors in hepatitis B patients may help to prevent the development of HCC. FGF4 and GH were found, for the first time, to be upregulated in HCC, suggesting that these two growth factors may serve as novel serum biomarkers for the early diagnosis of HCC. Conclusion: The combined detection of all the differential growth factors may improve the diagnostic accuracy of HCC.

The effects of Ag and/or Cu additions on the natural aging and precipitation hardening behavior of Al-Mg-Si alloys were investigated by using hardness test, differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Both Ag and Cu additions enhanced the hardening kinetics of Al-Mg-Si alloys during natural aging (NA) and artificial aging (AA) treatments. The strong interaction of Cu, Ag and Mg atoms is responsible for the improved precipitation kinetics of these alloys, resulting in a refinement of clusters and precipitates. The stronger interaction between Ag and Mg results in lower T4 hardness and higher AA hardness, compared to Cu. This is potentially beneficial for automobile applications where rapid hardening during paint baking is required. Both Ag and Cu additions reduce the detrimental effect of NA on subsequent AA, due to the formation of Ag or Cu-containing clusters. The clear advantage of Ag addition, compared to Cu, is the improvement of precipitation hardening response of Al-Mg-Si alloys.

To investigate the role of NF-κB in TNF-α induced apoptosis in HSC-T6, a mutant IκBα was transfected into HSC-T6 cells by lipofectin transfection technique and its transient effect was examined 48 h after the transfection. The activation of NF-κB was detected by immune fluorescence cytochemistry and Western blotting with anti-p65 antibody. The apoptosis and the rate of inhibition by TNF-α in both transfected and untransfected HSC-T6 cells were measured respectively by FAC-Scan side scatter analysis and MTT methods. Our results showed that TNF-α could activate NF-κB in untransfected cells but not in transfected HSC-T6 cells. The percentage of apoptosis in transfected cells were significantly higher than that in the untransfected ones (P

To investigate the role of NF-kappaB in TNF-alpha induced apoptosis in HSC-T6, a mutant IkappaBalpha was transfected into HSC-T6 cells by lipofectin transfection technique and its transient effect was examined 48 h after the transfection. The activation of NF-kappaB was detected by immune fluorescence cytochemistry and Western blotting with anti-p65 antibody. The apoptosis and the rate of inhibition by TNF-alpha in both transfected and untransfected HSC-T6 cells were measured respectively by FAC-Scan side scatter analysis and MTT methods. Our results showed that TNF-alpha could activate NF-kappaB in untransfected cells but not in transfected HSC-T6 cells. The percentage of apoptosis in transfected cells were significantly higher than that in the untransfected ones (P0.01) and it was also true of the inhibition rate (P0.01). It is concluded that the resistance of HSC-T6 towards apoptosis induced by TNF-alpha can be mediated by NF-kappaB activation. The inhibition of NF-kappaB activation by mutant IkappaBalpha can attenuate the resistance of HSC-T6 cells and increase its sensitivity to TNF-alpha.