Scoping review of obesity interventions: Research frontiers and publication status.

Obesity and overweight are significant global health issues, and numerous obesity intervention studies have been conducted. Summarizing current knowledge of interventions aims to inform researchers and policymakers to keep up-to-date with the latest scientific advancements and trends. In this review, we comprehensively retrieved and screened 4,541 studies on obesity intervention published between 2018 and 2022 in the Web of Science Core Collection, and objectively presented research frontiers using bibliometric analysis. The research frontiers of intervention are mainly focused on dietary, exercise, pharmacological interventions, bariatric surgery, environmental, and cognitive interventions. Time-restricted eating is the hottest research topic, followed by probiotics and Roux-en-Y gastric bypass. Gut microbiota is located in the "Basic and transversal themes" quadrant with a high centrality and low density, which has great development potentiality. Obesity intervention is becoming increasingly common,and we advocate for researchers to undertake more focused research endeavors that consider the specific characteristics of diverse populations or patients.

Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma.

Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field. Within the tumor microenvironment, PD-L1 expression is commonly utilized to predict response. Moreover, the characteristics of tumor-infiltrating lymphocytes are associated with the effectiveness of immunotherapy. Preclinical studies have identified stimulatory dendritic cells, conventional dendritic cells, and macrophages as potential biomarkers. The emergence of single-cell sequencing and spatial transcriptomics has provided invaluable insights into tumor heterogeneity through the lens of single-cell profiling and spatial distribution. With the widespread adoption of next-generation sequencing, certain genomic characteristics, including tumor mutational burden, copy number alterations, specific genes (TP53, CTNNB1, and GZMB), and signaling pathways (WNT/ß-catenin) have been found to correlate with prognosis. Furthermore, clinical features such as tumor size, number, and metastasis status have demonstrated prognostic value. Notably, common indicators such as the Child-Pugh score and Eastern Cooperative Oncology Group score, which are used in patients with liver diseases, have shown potential. Similarly, commonly employed laboratory parameters such as baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes in alpha-fetoprotein (AFP) and abnormal prothrombin, CRAFITY score (composed of C-reactive protein and AFP), and immune adverse events have been identified as predictive biomarkers. Novel imaging techniques such as EOB-MRI and PET/CT employing innovative tracers also have potential. Moreover, liquid biopsy has gained widespread use in biomarker studies owing to its non-invasive, convenient, and highly reproducible nature, as well as its dynamic monitoring capabilities. Research on the gut microbiome, including its composition, dynamic changes, and metabolomic analysis, has gained considerable attention. Efficient biomarker discovery relies on continuous updating of treatment strategies. Next, we summarized recent advancements in clinical research on HCC immunotherapy and provided an overview of ongoing clinical trials for contributing to the understanding and improvement of HCC immunotherapy.

Lenvatinib combined with PD-1 inhibitor plus Gemox chemotherapy versus plus HAIC for advanced biliary tract cancer.

OBJECTIVE: To compare the treatment efficacy and safety of lenvatinib and programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin plus gemcitabine (Gemox) chemotherapy or hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancer (BTC). METHOD: This study involved 86 patients with advanced BTC receiving PD-1 inhibitor and lenvatinib combined with HAIC (P-L-H group) or Gemox chemothrapy (P-L-G group). Propensity score matching (PSM) (1:1) analysis was used to balance potential bias. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. RESULT: After PSM, a total of 60 patients were enrolled with 30 in the P-L-G group and 30 in the P-L-H group. The median PFS was significantly longer with P-L-G group (13.7 versus 6.0 months, p < 0.0001) than with the P-L-H group. The median OS was 23.8 months in the P-L-G group versus 11.6 months in the P-L-H group (p < 0.0001). Patients in the P-L-G group exhibited a better ORR (73.3 % vs 30 %, p = 0.002) compared to the P-L-H group. The DCR was the same in both groups, 96.7 %, respectively. The P-L-G group had a higher incidence of grade 3-4 AEs than the P-L-H group. However, there was no significant difference in the any grade or grade 3-4 of AEs between the two groups. CONCLUSION: PD-1 inhibitor plus lenvatinib and Gemox are promising first-line regimens for the treatment of advanced BTC in the multicenter retrospective real-world study.

Genome-Wide Identification of Catalase Gene Family and the Function of SmCAT4 in Eggplant Response to Salt Stress.

Salinity is an important abiotic stress, damaging plant tissues by causing a burst of reactive oxygen species (ROS). Catalase (CAT) enzyme coded by Catalase (CAT) genes are potent in reducing harmful ROS and hydrogen peroxide (H2O2) produced. Herein, we performed bioinformatics and functional characterization of four SmCAT genes, retrieved from the eggplant genome database. Evolutionary analysis CAT genes revealed that they are divided into subgroups I and II. The RT-qPCR analysis of SmCAT displayed a differential expression pattern in response to abiotic stresses. All the CAT proteins of eggplant were localized in the peroxisome, except for SmCAT4, which localized in the cytomembrane and nucleus. Silencing of SmCAT4 compromised the tolerance of eggplant to salt stress. Suppressed expression levels of salt stress defense related genes SmTAS14 and SmDHN1, as well as increase of H2O2 content and decrease of CAT enzyme activity was observed in the SmCAT4 silenced eggplants. Our data provided insightful knowledge of CAT gene family in eggplant. Positive regulation of eggplant response to salinity by SmCAT4 provides resource for future breeding programs.

Efficacy and safety of subsequent radiotherapy in patients with advanced-stage hepatocellular carcinoma treated with immune checkpoint inhibitors.

Background: The development of immunotherapy resistance is associated with a poor prognosis in patients diagnosed with hepatocellular carcinoma (HCC) who are undergoing treatment with immune checkpoint inhibitors (ICI). This study aimed to evaluate the efficacy and safety of subsequent radiotherapy (RT) for patients with advanced-stage HCC who had lesion enlargement or new lesions (NLs) during ICI therapy. Methods: This retrospective observational study enrolled 36 patients with advanced-stage HCC who underwent subsequent RT for lesion enlargement or NLs during ICI therapy from two centers. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), 1- and 2-year local control (LC) rates, in-field PFS (IFPFS), out-field PFS (OFPFS), and safety. Results: The median follow-up time was 15.3 months. The median PFS was 7.4 months [95% confidence interval (CI): 3.1-11.7 months], and the median OS was 18.8 months (95% CI: 17.1-20.5 months). ORR and DCR were 38.9% and 72.2%, respectively. In addition, the median IFPFS was 17.8 months (95% CI: 11.5-24.2 months), median OFPFS was 7.9 months (95% CI: 3.4-12.5 months), and estimated 1- and 2-year LC rates were 67.1% and 31.9%, respectively. The most common treatment-related adverse events (all grades) were diarrhea (33.3%), rash (30.6%), and malaise (27.8%); a total of 14 (38.9%) patients developed grade 3-4 AEs. Conclusions: Subsequent RT showed reliable antitumor effects and an acceptable safety profile in patients with advanced-stage HCC who had unsatisfactory response to ICI therapy; therefore, it could serve as an optional salvage strategy.

SmWRKY11 acts as a positive regulator in eggplant response to salt stress.

Salt stress is one of the most threatening abiotic stresses to plants, which can seriously affect plant growth, development, reproduction, and yield. However, the mechanisms of plant against salt stress largely remain unclear. Herein, SmWRKY11, an assumed WRKY transcription factor, was functionally characterized in eggplant against salt stress. SmWRKY11 was significantly up-regulated by salt, dehydration stress, and ABA treatment. SmWRKY11 located in the nucleus, and the Plant_zn_clust conserved domain exhibited transcriptional activation activity. Silencing of SmWRKY11 enhanced the susceptibility of eggplant to salt stress, accompanied by significantly down-regulation of transcript expression levels of salt stress defense-related genes SmNCED1, SmGSTU10, and positive regulator of salt stress response SmERF1 as well as increase of hydrogen peroxide (H2O2) content and decrease of the enzyme activities of catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX). In addition, silencing of SmERF1 also could significantly down-regulate SmWRKY11 expression in eggplant response to salt stress. By luciferase reporter assay and chromatin immunoprecipitation PCR assay, SmERF1 expression was found to be indirectly activated by SmWRKY11. These data indicate that SmWRKY11 acts as a positive regulator by forming positive feedback loop with SmERF1 via an indirect regulatory manner in eggplant response to salt stress.

Real-world cohort study of PD-1 blockade plus lenvatinib for advanced intrahepatic cholangiocarcinoma: effectiveness, safety, and biomarker analysis.

BACKGROUND: In clinical practice, some patients with advanced intrahepatic cholangiocarcinoma (ICC) cannot tolerate or refuse chemotherapy due to the toxicity, necessitating alternative treatments. PD-1 blockade combined with lenvatinib showed promising results in phase II studies with small sample size, but there is a lack of data on the routine use with this regimen. This study aimed to evaluate the effectiveness and safety of the regimen in patients with advanced ICC, and to identify predictors for treatment response and prognosis. METHODS: We conducted a retrospective cohort study of patients treated with PD-1 inhibitors plus lenvatinib for advanced ICC between July 2017 and August 2022. The study endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Biomarker analysis for CA19-9 and PD-L1 expression was performed. Exploratory analysis for genetic alternation was conducted. RESULTS: The study included 103 patients. It demonstrated a median PFS of 5.9 months and a median OS of 11.4 months. ORR was 18.4% and DCR was 80.6%. The incidence of grade 3 or 4 adverse events was 50.5%. Positive PD-L1 expression (TPS ≥ 1%) was associated with higher ORR (P = 0.013) and prolonged PFS (P = 0.023). Elevated CA19-9 (> 37 U/ml) was associated with decreased ORR (P = 0.019), poorer PFS (P = 0.005) and OS (P = 0.034). Patients with IDH1 mutations exhibited a favorable response to the treatment (P = 0.011), and patients with TP53 mutations tended to have worse OS (P = 0.031). CONCLUSIONS: PD-1 blockade plus lenvatinib is effective and safe in routine practice. PD-L1 expression and CA19-9 level appear to predict the treatment efficacy. IDH1 mutations might indicate a better treatment response. CLINICAL TRIAL REGISTRATION: NCT03892577.

Genome-Wide Exploration and Expression Analysis of the CNGC Gene Family in Eggplant (Solanum melongena L.) under Cold Stress, with Functional Characterization of SmCNGC1a.

Eggplant (Solanum melongena L.) is an important economic crop, and to date, there has been no genome-wide identification and analysis of the cyclic nucleotide-gated channel (CNGC) gene family in eggplant. In this study, we identified the CNGC gene family in eggplant, and the results showed that 29 SmCNGC genes were classified into five groups, unevenly distributed across the 12 chromosomes of eggplant. The gene structure and motif analysis indicated that the SmCNGC family proteins may exhibit apparent preferences during evolution. Furthermore, our study revealed the presence of numerous light-responsive elements, hormone-responsive elements, and transcription factor binding sites in the promoter regions of SmCNGC genes, suggesting their significant role in environmental adaptability regulation. Finally, we analyzed the expression patterns of all SmCNGC genes under cold stress and found that SmCNGC1a was significantly upregulated under cold stress. Subcellular localization experiments indicated that this gene is located on the plasma membrane. Subsequently, its importance in the low-temperature response of eggplant was validated through virus-induced gene silencing (VIGS), and its protein interactome was predicted. In summary, our study provides a comprehensive understanding of the function and regulatory mechanisms of the CNGC gene family in eggplant, laying an important foundation for further research on cold adaptation in eggplant.

The efficacy and safety of bevacizumab as a salvage therapy for patients with advanced hepatocellular carcinoma targeting immune tolerance.

As is well understood that malignant tumour progression requires additional blood vessels to provide the nutrients necessary for growth. Many patients with advanced hepatocellular carcinoma (aHCC) experience disease progression after treatment with lenvatinib (Lenva) and immune checkpoint inhibitors (ICIs). Therefore, we designed a double-arm retrospective study to evaluate the antitumour activity of additional bevacizumab (Beva, an anti-vascular endothelial growth factor-targeting drug) as a means to reduce the blood vessels needed for tumour growth. Compared with the control group, the group that received Beva had prolonged progression-free survival (PFS) and a trend toward a benefit for overall survival duration. This study aimed to evaluate the anticancer effect of Beva in patients with aHCC who experienced tumour progression after treatment with Lenva+ICIs. From April 2021 to March 2023, we retrospectively included 20 patients as the experimental group and 21 patients as the control group. The patients in the experimental group experienced disease progression after receiving targeted therapy and ICIs, after which we added Beva to the treatment. The patients in the control group only received targeted therapy and ICIs. The efficacy endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), which were evaluated according to RECIST v1.1. Adverse events were assessed using NCI-CTCAE v5.0. Ultimately, 20 patients with aHCC in the experimental group of received Beva after disease progression, compared with 21 patients in the control group. The median OS was 12.6 mo (95% CI: 6.8-18.7) vs. 9.3 mo (95% CI: 4.3-14.4), and the median PFS was 6.9 mo (95% CI: 6.4-7.4) vs. 4.1 mo (95% CI: 2.4-5.8). The ORR for all patients was 5%, and the DCR for all patients was 70.0%. The median follow-up time for all patients was 7.5 mo (95% CI: 5.0-10.0). All patients had adverse events, but no fatal adverse events were observed. In conclusion, Bevacizumab is a drug resistant treatment option for patients with advanced hepatocellular carcinoma after Lenva+PD-1/PD-L1 treatment.

Genome-Wide Identification and Expression Analysis of Respiratory Burst Oxidase Homolog (RBOH) Gene Family in Eggplant (Solanum melongena L.) under Abiotic and Biotic Stress.

Respiratory burst oxidase homologs (RBOHs) are important proteins that catalyze the production of reactive oxygen species (ROS), which play important roles in growth and stress response. For a comprehensive analysis of SmRBOH genes, we conducted genome-wide identification of the SmRBOH gene family in eggplant (Solanum melongena L.) and analyzed the expression of SmRBOHs under abiotic (salt, high-temperature, and low-temperature) and biotic stress (Verticillium dahliae inoculation) by quantitative real-time PCR (qRT-PCR). The result showed that a total of eight SmRBOH members were identified from the genome database of eggplant, and they were relatively evenly distributed across seven chromosomes. The analysis of Motif and the conserved domain showed that SmRBOHs have high similarity in protein sequences and functions. Based on phylogenetics, SmRBOHs were classified into three distinct clades. Furthermore, the promoter regions of SmRBOHs were found to contain different cis-elements. Additionally, the results of the qRT-PCR demonstrated differential expression patterns of SmRBOHs in different tissues (the roots, stems, and leaves) and stress conditions. SmRBOHB, SmRBOHD, SmRBOHH1, and SmRBOHH2 showed significant upregulation (>20-fold) under at least one stress condition. Subcellular localization analysis of the above four members further confirmed that they localized on the plasma membrane. This study provides a theoretical foundation for understanding the functions of SmRBOHs in eggplant.

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study.

BACKGROUND: A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world study. METHODS: Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed. RESULTS: Fifty-three patients with advanced ICC were included in this study. The median follow-up time was 13.7 (95% confidence interval (CI): 12.9-17.2) months. The median OS and PFS were 14.3 (95% CI: 11.3-NR) and 8.63 (95% CI: 7.17-11.6) months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, and 75.5%, respectively. In the multivariate analysis, the tumor burden score (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression were independent prognostic factors for OS and PFS. All patients experienced adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were reported. CONCLUSION: PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy represent an effective and tolerable regimen for advanced ICC in a multicenter retrospective real-world study. TBS, TNM stage, and PD-L1 expression can be used as potential prognostic factors for OS and PFS.

Mechanisms influencing the factors of urban built environments and coronavirus disease 2019 at macroscopic and microscopic scales: The role of cities.

In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.

Clinical outcomes of lenvatinib plus transarterial chemoembolization with or without programmed death receptor-1 inhibitors in unresectable hepatocellular carcinoma.

BACKGROUND: Programmed death receptor-1 (PD-1) inhibitors have been approved as second-line treatment regimen in hepatocellular carcinoma (HCC), but it is still worth studying whether patients can benefit from PD-1 inhibitors as first-line drugs combined with targeted drugs and locoregional therapy. AIM: To estimate the clinical outcome of transarterial chemoembolization (TACE) and lenvatinib plus PD-1 inhibitors for patients with unresectable HCC (uHCC). METHODS: We carried out retrospective research of 65 patients with uHCC who were treated at Peking Union Medical College Hospital from September 2017 to February 2022. 45 patients received the PD-1 inhibitors, lenvatinib, TACE (PD-1-Lenv-T) therapy, and 20 received the lenvatinib, TACE (Lenv-T) therapy. In terms of the dose of lenvatinib, 8 mg was given orally for patients weighing less than 60 kg and 12 mg for those weighing more than 60 kg. Of the patients in the PD-1 inhibitor combination group, 15 received Toripalimab, 14 received Toripalimab, 14 received Camrelizumab, 4 received Pembrolizumab, 9 received Sintilimab, and 2 received Nivolumab, 1 with Tislelizumab. According to the investigators' assessment, TACE was performed every 4-6 wk when the patient had good hepatic function (Child-Pugh class A or B) until disease progression occurred. We evaluated the efficacy by the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria). We accessd the safety by the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0. The key adverse events (AEs) after the initiation of combination therapy were observed. RESULTS: Patients with uHCC who received PD-1-Lenv-T therapy (n = 45) had a clearly longer overall survival than those who underwent Lenv-T therapy (n = 20, 26.8 vs 14.0 mo; P = 0.027). The median progression-free survival time between the two treatment regimens was also measured {11.7 mo [95% confidence interval (CI): 7.7-15.7] in the PD-1-Lenv-T group vs 8.5 mo (95%CI: 3.0-13.9) in the Lenv-T group (P = 0.028)}. The objective response rates of the PD-1-Lenv-T group and Lenv-T group were 44.4% and 20% (P = 0.059) according to the mRECIST criteria, meanwhile the disease control rates were 93.3% and 64.0% (P = 0.003), respectively. The type and frequency of AEs showed little distinction between patients received the two treatment regimens. CONCLUSION: Our results suggest that the early combination of PD-1 inhibitors has manageable toxicity and hopeful efficacy in patients with uHCC.

Effectiveness and safety of radiotherapy plus programmed death-1 inhibitors and lenvatinib in patients with advanced biliary tract carcinoma: a real-world study.

BACKGROUND: Radiotherapy (RT) may function synergistically with immunotherapy and targeted agents (TA). This study aimed to assess the effectiveness and safety of RT combined with programmed death-1 (PD-1) inhibitors and lenvatinib in patients with relapsed or refractory advanced biliary tract carcinoma (BTC). METHODS: This retrospective study included patients with relapsed or refractory advanced BTC who received RT combined with PD-1 inhibitors and lenvatinib at the Peking Union Medical College Hospital (PUMCH). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. RESULTS: Thirty-one patients who received RT combined with PD-1 inhibitors and lenvatinib as a second- or later-line therapy were analyzed. RT sites were mainly distributed in the liver lesions (64.5%) and lymph nodes (58.1%). The ORR and DCR were 32.3% (10/31; 95% CI: 14.8-49.7) and 87.1% (27/31; 95% CI: 74.6-99.6), respectively. The median PFS (mPFS) and median OS (mOS) were 7.9 (95% CI: 7.1-8.7) and 11.7 (95% CI: 8.3-15.0) months, respectively. Subgroup analyses of this cohort included 12 and 19 patients who received concurrent and salvage (> 6 weeks after commencing PD-1 inhibitor therapy) RT, respectively. The salvage RT group had higher mOS (11.7 vs. 10.5; p = 0.75) and mPFS (7.9 vs. 6.9; p = 0.85) than the concurrent RT group; however, statistical significance was not reached. All patients experienced any-grade adverse events (AEs), and excessive PD-1 inhibitors or RT toxicity were not observed. CONCLUSIONS: RT, PD-1 inhibitors, and lenvatinib may be safely combined and have antitumor effectiveness in patients with advanced BTC.

Safety and feasibility of toripalimab plus lenvatinib with or without radiotherapy in advanced BTC.

Background: Toripalimab shows antitumor efficacy in cholangiocarcinoma. Radiotherapy (RT) may enhance systemic responses of PD-1 inhibitors and lenvatinib. This study was designed to assess the safety and feasibility of toripalimab plus lenvatinib with or without RT in advanced BTC. Methods: This study involved 88 patients with advanced BTC receiving toripalimab plus lenvatinib with or without RT from the clinical trials (NCT03892577). Propensity score matching (PSM) (1:1) analysis was used to balance potential bias. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) were evaluated. Results: After PSM, the final analysis included 40 patients: 20 receiving toripalimab plus lenvatinib without RT (NRT); 20 receiving toripalimab plus lenvatinib with RT. The AEs were more frequent in the RT group than in the NRT group without treatment-associated mortality. The addition of RT did not cause specific AEs. The median PFS was significantly longer with RT (10.8 versus 4.6 months, p<0.001). The median OS was 13.7 months with RT versus 9.2 months in the NRT group (p=0.008). The ORR was 35% (95% CI: 12.1-57.9) in the RT group versus 20% (95% CI: 0.8-39.2) in the NRT group. Conclusions: The addition of RT may enhance the efficacy of toripalimab plus lenvatinib. Toripalimab plus lenvatinib with RT have a good safety profile without an increase in specific toxicities in advanced BTC patients.

Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer.

Background: Lenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study. Methods: Patients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated. Results: Fifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6-19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0-NA), and 9.27 (95% CI: 7.1-11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%-56.7%), 91.2% (95% CI: 81.1%-96.2%), and 73.7% (95% CI: 61.0%-83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P<0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported. Conclusion: Lenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC.

[Frontiers and development in live-cell super-resolution fluorescence microscopy].

This paper reviews the research progress on live-cell super-resolution fluorescence microscopy, discusses the current research status and hotspots in this field, and summarizes the technological application of super-resolution fluorescence microscopy for live-cell imaging. To date, this field has gained progress in numerous aspects. Specifically, the structured illumination microscopy, stimulated emission depletion microscopy, and the recently introduced minimal photon fluxes microscopy are the current research hotspots. According to the current progress in this field, future development trend is likely to be largely driven by artificial intelligence as well as advances in fluorescent probes and relevant labelling methods.

High-Performance Organohydrogel Artificial Muscle with Compartmentalized Anisotropic Actuation Under Microdomain Confinement.

Current hydrogel actuators mostly suffer from weak actuation strength and low responsive speed owing to their solvent diffusion-induced volume change mechanism. Here a skeletal muscle-inspired organohydrogel actuator is reported in which solvents are confined in hydrophobic microdomains. Organohydrogel actuator is driven by compartmentalized directional network deformation instead of volume change, avoiding the limitations that originate from solvent diffusion. Organohydrogel actuator has an actuation frequency of 0.11 Hz, 110 times that of traditional solvent diffusion-driven hydrogel actuators (<10-3  Hz), and can lift more than 85 times their own weight. This design achieves the combination of high responsive speed, high actuation strength, and large material size, proposing a strategy to fabricate hydrogel actuators comparable with skeletal muscle performance.

High incidence combination of multiple primary malignant tumors of the digestive system.

BACKGROUND: Clinical reports of multiple primary malignant tumors (MPMTs) in the digestive system are increasing. In China, although the survival rate of patients with MPMTs is increasing, the quality of life is very low. Many patients have reached the advanced stage when the second primary tumor is found, resulting in no early intervention and treatment. This is due to the misunderstanding of MPMTs by clinicians, who treat such tumors as metastases. Therefore, before a patient has a second primary tumor, doctors should understand some common combinations of digestive system MPMTs to provide clinical guidance to the patient. AIM: To explore the high incidence combination of digestive system MPMTs under heterochronism and synchronization. METHODS: A total of 1902 patients with MPMTs at Peking Union Medical College Hospital were analyzed retrospectively. They were divided into metachronous MPMT and synchronous MPMT groups, and then the high incidence combinations of the first primary cancer and the second primary cancer in metachronous cancer and synchronous cancer were sorted. Sex and age differences between metachronous and synchronous tumors were tested by the chi square test and t test, respectively. A P value < 0.05 was considered as statistically significant, and SPSS version 26.0 (SPSS Inc., Chicago, Illinois, United States) was used for statistical analysis. RESULTS: Among the 1902 patients with MPMTs confirmed by pathology, 1811 (95.2%) cases were secondary primary cancers, 89 (4.7%) cases were tertiary primary cancers, and 2 (0.1%) cases were quaternary primary cancers. Most (88.2%) of the secondary primary cancers were identified as metachronous multiple primary cancers six months after diagnosis of the first primary cancer. The top ten most common MPMTs in the first primary cancer group ranged from high to low as follows: Breast cancer, thyroid cancer, nonuterine cancer, lung cancer, colon cancer, kidney cancer, uterine cancer, bladder cancer, rectal cancer, and gastric cancer. The highest incidence rate of the first primary cancer in male metachronous cancer was lung cancer (11.6%), the highest incidence rate of the second primary cancer was still lung cancer (24.9%), the highest incidence rate of the first primary cancer in female metachronous cancer was breast cancer (32.7%), and the highest incidence rate of the second primary cancer was lung cancer (20.8%). Among them, breast cancer, nonuterine cancer and uterine cancer were female-specific malignant tumor types, and thyroid cancer also accounted for 79.6% of female patients. The top five metachronous cancer combinations, independent of female-specific malignant tumor types and thyroid cancer, were colon cancer and lung cancer (26 cases), kidney cancer and lung cancer (25 cases), rectal cancer and lung cancer (20 cases), gastric cancer and lung cancer (17 cases), and bladder cancer and lung cancer (17 cases). The most common synchronous cancer combination was colon cancer and rectal cancer (15 cases). CONCLUSION: Screening for lung cancer should be performed six months after the detection of colon cancer while rectal cancer screening should be performed within six months.

Novel cellular therapies for hepatobiliary malignancies.

BACKGROUND: The mortalities of hepatobiliary malignancies are high. With the failure of conventional chemotherapy and unsatisfactory outcome of molecular targeted drugs, immune-based therapy has become a new focus of research in hepatobiliary cancers treatment. DATA SOURCES: We performed a PubMed search with relevant articles published up to May 2022 and the following keywords: cellular immunotherapy, hepatobiliary cancer, antigen receptor T cell therapy, and receptor-engineered T cell. Information of clinical trials was obtained from https://clinicaltrials.gov/. RESULTS: Cell therapies for hepatobiliary malignancies are at early stage of development. The current review showed that cellular therapies are safe and feasible in patients. These findings provide an important platform for future lager scale clinical trials on immunotherapy in patients with hepatobiliary malignancies. CONCLUSIONS: With the continuous advances of cellular immunotherapy, the combination of cellular immunotherapy with surgery, chemotherapy and radiotherapy will be new therapeutic strategies for patients with hepatobiliary cancer.