Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy.

Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

Predictive value of machine learning models for lymph node metastasis in gastric cancer: A two-center study.

BACKGROUND: Gastric cancer is one of the most common malignant tumors in the digestive system, ranking sixth in incidence and fourth in mortality worldwide. Since 42.5% of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type, the application of imaging diagnosis is restricted. AIM: To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning (ML) algorithms and to evaluate their predictive performance in clinical practice. METHODS: Data of a total of 369 patients who underwent radical gastrectomy at the Department of General Surgery of Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) from March 2016 to November 2019 were collected and retrospectively analyzed as the training group. In addition, data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People's Hospital (Jining, China) were collected and analyzed as the verification group. Seven ML models, including decision tree, random forest, support vector machine (SVM), gradient boosting machine, naive Bayes, neural network, and logistic regression, were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer. The ML models were established following ten cross-validation iterations using the training dataset, and subsequently, each model was assessed using the test dataset. The models' performance was evaluated by comparing the area under the receiver operating characteristic curve of each model. RESULTS: Among the seven ML models, except for SVM, the other ones exhibited higher accuracy and reliability, and the influences of various risk factors on the models are intuitive. CONCLUSION: The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer, which can aid in personalized clinical diagnosis and treatment.

Meta-analysis of the clinical efficacy and safety of oblique lateral interbody fusion and transforaminal interbody fusion in the treatment of degenerative lumbar spondylolisthesis.

Objective: The aim of this study was to comprehensively evaluate the efficacy of oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of degenerative lumbar spondylolisthesis by meta-analysis. Methods: A computer-based search of PubMed, Cochrane Library, Embase, Web of Science Core Collection databases, the China National Knowledge Infrastructure, China Biology Medicine, and Wanfang Digital Periodicals was conducted from the time of inception of each database to December 2021. The review process was conducted according to the PRISMA guidelines and registered in the PROSPERO database. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library. Results: Thirteen studies were included in the statistical analysis. One randomized controlled study and 12 cohort studies with 954 patients were included. In terms of operation time, intraoperative blood loss, Oswestry disability index score, intervertebral height, and complications, the OLIF group was better than the TLIF group, and the difference was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of visual analogue scale score, lumbar lordosis or fused segment lordosis (P > 0.05). Conclusion: Both OLIF and TLIF are effective surgical modalities in the treatment of degenerative lumbar spondylolisthesis. They achieve similar therapeutic effects, but OLIF is superior to TLIF in restoring intervertebral height. At the same time, OLIF has the advantages of short operation time and less intraoperative blood loss.

Hulless Black Barley as a Carrier of Probiotics and a Supplement Rich in Phenolics Targeting Against H2O2-Induced Oxidative Injuries in Human Hepatocarcinoma Cells.

Lactic acid bacteria can provide benefits to human beings and transform phenolic substances to improve their potential functionality. It was of interest to develop black barley as a carrier of probiotics and nutraceutical supplement rich in more antioxidants. Due to fermentation, bacterial counting and free phenolic content in black barley increased to 9.54 ± 0.22 log cfu/mL and 5.61 ± 0.02 mg GAE/mL, respectively. Eleven phenolic compounds, including nine isoflavones and two nitrogenous compounds were characterized using UPLC-QTOF-MS, among which epicatechin, hordatine, and pelargonidin aglycone were largely enriched. Moreover, free phenolic extracts from fermented barley (F-BPE) played a greater role in scavenging DPPH radicals, reducing Fe3+ to Fe2+, and increasing oxygen radical absorbance capacity, compared phenolic extracts from unfermented barley [UF-BPE (1.94-, 1.71-, and 1.35-fold at maximum for F-BPE vs. UF-BPE, respectively)]. In hepatocarcinoma cells, F-BPE also better inhibited ROS production and improved cell viability, cell membrane integrity, SOD activity, and non-enzymatic antioxidant GSH redox status (2.85-, 3.28-, 2.05-, 6.42-, and 3.99-fold at maximum for F-BPE vs. UF-BPE, respectively).

Silver-Promoted Direct Phosphorylation of Bulky C(sp2)-H Bond to Build Fully Substituted ß-Phosphonodehydroamino Acids.

A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,ß-dehydro α-amino carboxylic esters and H-phosphites is described. This C(sp2)-H phosphorylation reaction proceeds with absolute Z-selectivity promoted by silver salt in a radical relay manner. The bulky tetrasubstituted ß-phosphonodehydroamino acids were obtained in grams and added new modules to the toolkit for peptide modifications.

Direct Enamido C(sp2 )-H Diphosphorylation Enabled by a PCET-Triggered Double Radical Relay: Access to gem-Bisphosphonates.

Herein we report a novel and straightforward protocol for the construction of valuable gem-BPs by means of proton-coupled electron-transfer (PCET)-triggered enamido C(sp2 )-H diphosphorylation. This reaction represents a rare example of realizing the challenging double C-P bond formation at a single carbon atom, thus providing facile access to a broad variety of structurally diverse bisphosphonates from simple enamides under silver-mediated conditions. Initial mechanistic studies demonstrated that the diphosphorylation involves two rounds of PCET-initiated radical relay process.

Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis.

Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.

Acquiring an effective CaO-based CO2 sorbent and achieving selective methanation of CO2.

CO2 capture, utilization, and storage are promising strategies to solving the problems of superfluous CO2 or energy shortage. Here, mechanochemical reduction of CO2 by a MgH2/CaH2 mixture was first performed, by which we achieve selective methanation of CO2 and acquire an effective CaO-based CO2 sorbent, simultaneously. The selectivity of methanation is near 100% and the yield of CH4 reaches 30%. Four MgO and carbon-doped CaO-based CO2 sorbents (MgO/CaO/C, MgO/2CaO/C, MgO/4CaO/C, and MgO/8CaO/C) were formed as solid products in these reactions. Among them, the MgO/4CaO/C sorbent shows high initial adsorption amount of 59.3 wt% and low average activity loss of 1.6% after 30 cycles. This work provides a novel, well-scalable, and sustainable approach to prepare an efficient inert additive-including CaO-based CO2 sorbent and selectively convert CO2 to CH4 at the same time.

[Impact assessment on enamel remineralization after orthodontic treatment with casein phosphopeptide calcium phosphate complex].

PURPOSE: To compare the effect on enamel demineralization following fluoride rinse or casein phosphopeptide calcium phosphate complex (CPP-ACP) after fixed appliance orthodontic treatment. METHODS: The study population consisted of 21 post-orthodontic patients (13 females, 8 males, 84 affected teeth) with white spot lesions (WSL). They were divided into 3 groups with 28 affected teeth in each group. Participants in the control group were brushed with fluoride toothpaste twice a day. Participants in the fluoride group were instructed to rinse the mouth with 20mL 0.01% sodium fluoride rinse in addition to brushing twice a day. Participants in CPP-ACP group were instructed to use tooth moss after brushing their teeth twice a day for 6 months. SPSS 17.0 software package was used to analyze the data. RESULTS: Within 6 months after orthodontic treatment, white spot lesions areas of the three groups caused by enamel demineralization were all reduced in different degrees, and the differences of success rate were significant among three groups (P<0.05). CPP-ACP group achieved the highest success rate (51%) than the other group, the fluoride group (44%) and the control group (42%). CONCLUSIONS: Brushing teeth, fluoride rinse and CPP-ACP have certain effect on remineralization of demineralized teeth in 6 months after orthodontic treatment. Compared with brushing and fluoride rinse, CPP-ACP can reduce the area of enamel demineralization more effectively.