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Deformation of nanocrystalline materials often involves the grain boundary (GB) dominated creep process. However, the atomistic mechanism of diffusional mass transport along GB remains unclear. Here, we presented a mechanism of stress-driven diffusional climb of GB dislocations in gold (Au) nanocrystals by in-situ nanomechanical testing. Successive proceeding of GB dislocation climb enhances the mass transport along GBs and contributes to a Coble-type GB deformation at room temperature. These findings provide insights into the GB-dominated diffusional plasticity in nanocrystalline materials and are of significance for the creep deformation of nanocrystalline materials.

The objective of current experiment was to study the potential influence of hydrolysable tannin supplementation on slaughter performance, meat quality, intestinal digestive enzyme activity, antioxidant ability and barrier function in fattening lambs. In total, 36 male Hu sheep lambs with similar body weight (15.83 ± 0.48 kg) and days in age (55 ± 2 d) were randomly assigned to one of three groups of 12 animals each: control without tannin (CON) and tannin supplementation groups (TA1, 3 g/d per lamb; TA2, 6 g/d per lamb). All the lambs were reared in individual hutches, and the experiment lasted for 60 d. On d 61, 8 lambs from each group were randomly selected to slaughter. Results showed that the serum diamine oxidase and lipopolysaccharide contents of TA2 group were higher (p

Background and aimThe prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy.MethodsFrom February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.ResultsThe follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%).ConclusionHAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

ObjectiveJianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth.Methods300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF.ResultsJPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration.ConclusionThese findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration.

Extrachromosomal DNAs (eccDNAs) frequently carry amplified oncogenes. This investigation aimed to examine the occurrence and role of eccDNAs in individuals diagnosed with advanced perihilar cholangiocarcinoma (pCCA) who exhibited distinct prognostic outcomes. Five patients with poor survival outcomes and five with better outcomes were selected among patients who received first-line hepatic arterial infusion chemotherapy from June 2021 to June 2022. The extracted eccDNAs were amplified for high-throughput sequencing. Genes associated with the differentially expressed eccDNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The differentially expressed bile eccDNA-related genes were used to construct a prognostic model. Across all 10 patients, a total of 19,024 and 3,048 eccDNAs were identified in bile and plasma, respectively. The concentration of eccDNA detected in the bile was 9-fold higher than that in plasma. The chromosome distribution of the eccDNAs were similar between bile and matched plasma. GO and KEGG pathway analyses showed enrichment in the mitogen-activated protein kinase (MAPK) and Wnt/β-catenin pathways in patients with poor survival outcomes. According to the prognostic model constructed by eccDNA-related genes, the high-risk group of cholangiocarcinoma patients displayed significantly shorter overall survival (p < 0.001). Moreover, the degree of infiltration of immunosuppressive cells was higher in patients in the high-risk group. In conclusion, EccDNA could be detected in bile and plasma of pCCA patients, with a higher concentration. A prognostic model based on eccDNA-related genes showed the potential to predict the survival and immune microenvironment of patients with cholangiocarcinoma.

Abstract Prognostic features in advanced perihilar cholangiocarcinoma (pCCA) patients who received first-line hepatic arterial infusion chemotherapy (HAIC) are unknown. The purpose of our study was to develop an applicable score based on serum inflammatory-tumor biomarkers to predict the survival of advanced pCCA patients who received first-line HAIC. In total, 106 advanced pCCA patients were enrolled as the training cohort. The optimal cutoff values of baseline variables were defined by the receiver operating characteristic method or according to previous publications. According to the results of Cox regression analysis, baseline neutrophil-to-lymphocyte ratio (NLR) > 3.19, carcinoembryonic antigen (CEA) > 10 ng/mL, and carbohydrate antigen 19-9 (CA19-9) > 200 U/mL were identified as independent survival predictors, which were used to develop the NLCECA score (NLR, CEA, and CA19-9). When including the NLCECA score in the multivariate analysis, the NLCECA score was the only independent predictor of survival. The risk of survival decreased by 111.9% for each 1-point increase in the NLCECA score. Additionally, the NLCECA score could also predict survival in another 33 patients in the validation cohort (P

This experiment aimed to study the effects of tannin supplementation on growth performance, rumen fermentation characteristics, apparent digestibility and serum biochemistry, and antioxidant and immune indexes in fattening lambs. A total of 36 male Hu sheep lambs (body weight = 15.83 ± 0.48 kg and days of age = 55 ± 2 d) were fed a high-concentrate diet and randomly divided into one of three groups of 12 animals each: control with no tannin (CON) and tannin treatments (TA1, 3 g/d per lamb; TA2, 6 g/d per lamb). The feeding experiment lasted for 60 d. The results showed that the average daily gain and ruminal propionate content of lambs in the TA1 group were higher (p < 0.05) than those in the CON group. Lambs fed tannin had significantly increased (p < 0.05) microbial protein and decreased (p < 0.05) ammonia nitrogen concentrations in the rumen. In addition, the crude protein and neutral detergent fiber digestibility of the TA2 group were significantly decreased (p < 0.05) as compared with the TA1 and CON groups, respectively. The serum concentrations of triglyceride, immunoglobulin A, and catalase and the total antioxidant capacity were higher (p < 0.05) in the TA1 group that those in the CON group, whereas an opposite trend of urea nitrogen, interleukin-1β, and malondialdehyde was found between the two groups. Also, tannin supplementation increased (p < 0.05) Lactobacillus and decreased (p < 0.05) Salmonella counts in the feces of lambs. Taken together, tannin supplementation can improve the growth performance, immunity, and antioxidant ability of fattening lambs fed a high-concentrate diet.

Abstract Long timber columns are widely used in traditional timber structures worldwide; however, many of them possess bearing capacity issues and have to be strengthened. The current study aims to develop the novel Hybrid fiber reinforced polymers (HFRP) sheets suitable for long timber columns. In the first stage, six HFRP sheets were designed, and the evaluation of these sheets was carried out by the tensile tests and the Scanning electron microscopy (SEM) tests. Secondly, for the compression test, two sets of 36 timber columns were designed utilizing six types of HFRP sheets. Finally, the effects of different sheet types and strengthening methods on the compressive performance of timber columns were investigated. The findings reveal that bidirectional HFRP sheets have excellent compressive performance for timber columns. In the case of using one-layer interval reinforcement, the bearing capacity can be increased by 22.27%, which is 12.15–17.81% higher than that of the unidirectional HFRP sheets. Compared with one-layer reinforcement, the two-layer reinforcement increased from 0.91% to 5.35%. The current study's findings are intended to provide an essential scientific foundation for the advancement of fiber-reinforced timber column technology and the preservation of the heritage of timber structures.

Background and aim: Transarterial chemoembolization combined with hepatic arterial infusion chemotherapy (TACE-HAIC) has shown encouraging efficacy in the treatment of unresectable hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict overall survival (OS) of patients with unresectable HCC treated with TACE-HAIC. Methods: A total of 591 patients with unresectable HCC treated with TACE-HAIC between May 2009 and September 2020 were enrolled. These patients were randomly divided into training and validation cohorts. The independent prognostic factors were identified with Cox proportional hazards model. The model's discriminative ability and accuracy were validated using concordance index (C-index), calibration plots, the area under the time-dependent receiver operating characteristic curve (AUC) and decision curve analyses (DCAs). Results: The median OS was 15.6 months. A nomogram was established based on these factors, including tumor size, vein invasion, extrahepatic metastasis, tumor number, alpha fetoprotein (AFP), and albumin-bilirubin (ALBI), to predict OS for patients with unresectable HCC treated with TACE-HAIC. The C-index of the nomogram were 0.717 in the training cohort and 0.724 in validation cohort. The calibration plots demonstrated good agreement between the predicted outcomes and the actual observations. The AUC values were better than those of three conventional staging systems. The results of DCA indicated that the nomogram may have clinical usefulness. The patients in the low-risk group had a longer OS than those in intermediate-risk and high-risk groups (P

Abstract Background Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy. Methods This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle. Results Among 47 patients, 32 (68%) were males. The median age was 61 (29–75). With a median follow-up of 22.2 months (3.7–50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0–13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events. Conclusions Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy.

MethodsThis was a single-arm historical cohort study of ESCC patients with synchronous or heterochronous LM between December 2014 and July 2021 at the Department of Gastrointestinal Oncology. The patients were treated with HAIC for LM, and regular image assessments were performed according to the judgment of the interventional physician. Liver progression-free survival (PFS), liver objective response rate (ORR), liver disease control rate (DCR), overall survival (OS), adverse events (AEs), treatment information, and basic characteristics were observed retrospectively.ResultsOverall, a total of 33 patients were enrolled in this study. All included patients received catheterized HAIC therapy, with a median of three (ranging from 2 to 6) sessions. The treatment response of liver metastatic lesions included partial response (PR) in 16 (48.5%) patients, stable disease (SD) in 15 (45.5%) patients, and progressive disease (PD) in two (6.1%) patients, for an ORR of 48.5% and a DCR of 93.9%. The median liver PFS was 4.8 months (95% confidence interval (CI): 3.0–6.6 months), and the median OS was 6.4 months (95% CI: 6.1–6.6 months). Patients who achieved PR at the liver metastasis site after HAIC were more likely to have a longer OS than those who achieved SD or PD. Grade 3 AEs occurred in 12 patients. The most common grade 3 AE was nausea, occurring in 10 (30.0%) patients, followed by abdominal pain in three (9.1%) patients. Only one patient showed grade 3 elevation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and one patient suffered from grade 3 embolism syndrome AEs. Grade 4 adverse events, followed by abdominal pain, occurred in one patient.ConclusionHepatic arterial infusion chemotherapy might be an option as a regional therapy for ESCC patients with LM, as it is acceptable and tolerable.

Abstract Background The association of contrast-enhanced MRI (CE-MRI) and the overall survival (OS) of biliary tract cancers (BTC) is ambiguous. Thus, the aim of this study is to evaluate the value of signal enhancement ratio (SER) and its early change in CE-MRI as biomarkers of survival after hepatic arterial infusion chemotherapy (HAIC) in BTC. Results One hundred and two BTC patients treated via HAIC with 3cir-OFF regimen between January 2011 and June 2020 were enrolled in this retrospective study. The median progression-free survival (PFS) and OS were 9.8 months [range 1.5–83.3 months, 95% confidence interval (CI) 7.789–11.811] and 14.2 months (range 1.8–83.3 months, 95% CI: 11.106–17.294), respectively. The cutoff value of SER before HAIC (SER0) was 1.04, and both median PFS and OS in the SER0 ≥ 1.04 group were longer than in the SER0 0 group was longer than in the ΔSER

Introduction: Atherosclerosis is the main cause of many cardiovascular diseases and contributes to morbidity and mortality worldwide. The formation of macrophage-derived foam cells plays a critical role in the early stage of atherosclerosis pathogenesis. Diterpenoids found in the flowers of Callicarpa rubella Lindl., a traditional Chinese medicine, have been reported to have anti-inflammatory activity. However, little is known about the effects of these diterpenoids on macrophage foam cell formation.Methods: A macrophage-derived foam cell formation model was established by treating RAW264.7 cells with oxidized low-density lipoprotein (ox-LDL) for 24 h. Oil red O staining were used to detect the intracellular lipids. The cholesterol efflux capacity was assayed by labeling cells with 22-NBD-cholesterol. Western blots and real-time PCRs were performed to quantify protein and mRNA expressions.Results: Two diterpenoid molecules, 14α-hydroxyisopimaric acid (C069002) and isopimaric acid (C069004), extracted from the flowers of Callicarpa rubella Lindl., significantly attenuated ox-LDL-induced foam cell formation in RAW264.7 macrophages. Further investigation showed that these two diterpenoids could promote cholesterol efflux from RAW264.7 macrophages to apolipoprotein A-I or high-density lipoproteins, which was associated with upregulated expression of ATP-binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα), and peroxisome proliferator-activated receptor-γ (PPARγ). Unexpectedly, the diterpenoids C069002 and C069004 failed to enhance the mRNA transcription of the ABCG1 gene in macrophage-derived foam cells induced by ox-LDL. To evaluate the effects of diterpenoids on macrophage foam cell formation and determine the underlying mechanism, two drugs (lovastatin and rosiglitazone) were used as positive controls. Although both drugs could reduce macrophage foam cell formation and promote cholesterol efflux, they each had distinctive abilities to modulate the expression of cholesterol efflux-related genes. In contrast to lovastatin, rosiglitazone showed a similar influence on the expression of cholesterol efflux-related genes (including ABCA1, LXRα, and PPARγ) as the diterpenoids regardless of the presence or absence of ox-LDL, implying a similar mechanism by which they may exert atheroprotective effects.Conclusion: Our research indicates that diterpenoids effectively inhibit ox-LDL-induced macrophage foam cell formation by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1 pathway. Further investigation of diterpenoids as potential drugs for the treatment of atherosclerosis is warranted.

The objective of this experiment was to investigate the potential benefits of active dry yeast (ADY) on the growth performance, rumen fermentation, nutrient digestibility, and serum parameters of weaned beef calves. Thirty Simmental crossbred male calves (body weight = 86.47 ± 4.41 kg and 70 ± 4 d of age) were randomly divided into 2 groups: control (CON) (fed basal ration) and ADY (fed basal ration and 5 g/d ADY per calf). The dietary concentrate-to-roughage ratio was 35:65. All the calves were regularly provided rations 3 times a day at 07:00, 13:00, and 19:00 and had free access to water. The experiment lasted for 60 d. The average daily gain of ADY group was higher (P = 0.007) than that of the CON group, and the ratio of feed intake to average daily gain in the ADY group was reduced (P = 0.022) as compared to the CON group. The concentration of ruminal ammonia-N was higher (P = 0.023) in the CON group than that in the ADY group, but an opposite trend of microbial protein was found between the 2 groups. Also, the ruminal concentrations of propionate and butyrate were higher (P

Abstract Background The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment. Methods This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5–7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed. Results The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1–13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively. Conclusions The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.

BackgroundThe purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM).MethodsPatients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events.Results113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838–6.762]) and 4.6 months [95% CI, 3.419–5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828–21.372] and 13.1 months [95% CI, 11.215–14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms.ConclusionHAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT02557490.

Metallic nanowires (NW) usually exhibit unique physical, mechanical, and chemical properties compared to their bulk counterparts. Despite extensive research on their mechanical behavior, the atomic-scale deformation mechanisms of metallic nanowires remain incompletely understood. In this study, we investigate the deformation behavior of Au nanowires embedded with a longitudinal twin boundary (TB) under different loading rates using in situ nanomechanical testing integrated with atomistic simulations. The Au nanowires exhibit a recoverable bending strain of up to 27.5% with the presence of TBs. At low loading rates, the recoverable bending is attributed to the motion of stacking faults (SFs) and their interactions with TBs. At higher loading rates, the formation of high-angle grain boundaries and their reversible migration become dominant in Au nanowires. These findings enhance our understanding of the bending behavior of metallic nanowires, which could inspire the design of nanodevices with improved fatigue resistance and a large recoverable strain capacity.

Abstract The experiment was conducted to compare the growth performance, rumen fermentation, nutrient digestibility, and ruminal and fecal bacterial community between yaks and cattle-yaks. Ten male yaks (36-month-old) were used as the yak (YAK) group and 10 male cattle-yaks with similar age were selected as the cattle-yak (CAY) group. All the animals were fed same ration and the experiment lasted for 60 days. The results showed that the average daily gain and dry matter intake of CAY group were higher (P

Objective: This study aimed to introduce and evaluate a new embolization technique for the right gastric artery (RGA) during percutaneous implantation of a port-catheter system for hepatic arterial infusion chemotherapy (HAIC). Methods: From January 2013 to January 2017, 159 patients with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In 86 of these patients (56 men; aged 28–88 years; mean: 60.6 ​± ​12.0 years), in whom the RGA was obvious on arteriography, embolization of RGA was attempted using microcoils to protect the gastric mucosa during HAIC. In the first phase (first three years), antegrade embolization of the RGA using a 2.7 Fr microcatheter was performed in 55 patients. In the second phase (next two years), embolization of the RGA was attempted by combining antegrade embolization and retrograde embolization through the left gastric artery (LGA) in 31 patients. The success rates and the incidence of acute gastroduodenal mucosal toxicity (AGMT) in these two groups were compared. Results: The total success rate of the RGA embolization was 70.9%. The success rate was 83.9% in 31 patients who underwent combined antegrade and retrograde embolization, which was significantly higher than that of antegrade embolization alone (63.6%) performed in 55 patients (p ​= ​0.047). No complications related to embolization of RGA were documented. The incidence of AGMT was 29.1% (16/55) in patients in the first phase, which was significantly higher than that in the patients in the second phase (9.7%, 3/31) (p ​= ​0.037). Conclusion: A combination of retrograde embolization via LGA could increase the success rates of RGA embolization and reduce the incidence of AGMT after HAIC.

Crystal defects critically influence surface chemical reactions in nanomaterials, yet the basic mechanisms at play are still elusive. Here, the authors show the atomic-scale dynamics of surface oxidation at coherent planar defects in Ag and Pd, revealing how twins and stacking-faults selectively oxidize metallic nanocrystals.

BackgroundDigital health technologies (ie, the integration of digital technology and health information) aim to increase the efficiency of health care delivery; they are rapidly adapting to health care contexts to provide improved medical services for citizens. However, contrary to expectations, their rapid adoption appears to have led to health inequities, with differences in health conditions or inequality in the distribution of health care resources among different populations. ObjectiveThis scoping review aims to identify and describe the inequities of health care services brought about by the adoption of digital health technologies. The factors influencing such inequities, as well as the corresponding countermeasures to ensure health equity among different groups of citizens, were also studied. MethodsPrimary studies and literature, including articles and reviews, published in English between 1990 and 2020 were retrieved using appropriate search strategies across the following three electronic databases: Clarivate Analytics’ Web of Science, PubMed, and Scopus. Data management was performed by two authors (RY and WZ) using Thomson Endnote (Clarivate Analytics, Inc), by systematically screening and identifying eligible articles for this study. Any conflicts of opinion were resolved through discussions with the corresponding author. A qualitative descriptive synthesis was performed to determine the outcomes of this scoping review. ResultsA total of 2325 studies were collected during the search process, of which 41 (1.76%) papers were identified for further analysis. The quantity of literature increased until 2016, with a peak in 2020. The United States, the United Kingdom, and Norway ranked among the top 3 countries for publication output. Health inequities caused by the adoption of digital health technologies in health care services can be reflected in the following two dimensions: the inability of citizens to obtain and adopt technology and the different disease outcomes found among citizens under technical intervention measures. The factors that influenced inequities included age, race, region, economy, and education level, together with health conditions and eHealth literacy. Finally, action can be taken to alleviate inequities in the future by government agencies and medical institutions (eg, establishing national health insurance), digital health technology providers (eg, designing high-quality tools), and health care service recipients (eg, developing skills to access digital technologies). ConclusionsThe application of digital health technologies in health care services has caused inequities to some extent. However, existing research has certain limitations. The findings provide a comprehensive starting point for future research, allowing for further investigation into how digital health technologies may influence the unequal distribution of health care services. The interaction between individual subjective factors as well as social support and influencing factors should be included in future studies. Specifically, access to and availability of digital health technologies for socially disadvantaged groups should be of paramount importance.

A new synthetic method to flexible sensor towards NH3 with response magnitude as high as 4300% was based on vapor phase polymerization (VPP), where zinc oxide (ZnO) sheets were exposed to polyaniline (PANI) vapors on the flexible nonwoven fabric substrate. A possible brick wall masonry assembly structure of ZnO and PANI on the surface of nonwoven fabric was provided, which also possessed excellent mechanical flexibility and thermostability. The response value of flexible ZnO/PANI/nonwoven sensor increased from 5% to 4300% with the NH3 concentration varied over a wide range (0.5–10 ppm) at room temperature. Flexible and conductive ZnO/PANI/nonwoven composite material has good potential applications as NH3 gas sensor in environment monitoring components and wearable flexible devices.

Hepatocellular carcinoma (HCC) is characterized by a high rate of incidence and recurrence, and resistance to chemotherapy may aggravate the poor prognosis of HCC patients. Sorafenib resistance is a conundrum to the treatment of advanced/recurrent HCC. Therefore, studies on the molecular pathogenesis of HCC and the resistance to sorafenib are of great interest. Here, we report that GINS1 was highly expressed in HCC tumors, associated with tumor grades, and predicted poor patient survival using Gene Expression Omnibus (GEO) databases exploration. Cell cycle, cell proliferation assay and in vivo xenograft mouse model indicated that knocking down GINS1 induced in G1/S phase cell cycle arrest and decreased tumor cells proliferation in vitro and in vivo. Spheroid formation assay results showed that GINS1 promoted the stem cell activity of HCC tumor cells. Furthermore, GEO database (GSE17112) analysis showed that HRAS oncogenic gene set was enriched in GINS1 high-expressed cancer cells, and quantitative real-time PCR, and Western blot results proved that GINS1 enhanced HCC progression through regulating HRAS signaling pathway. Moreover, knocking down endogenous GINS1 with shGINS1 increased the sensitivity of HCC cells to sorafenib, and restoring HRAS or stem associated pathway partly recovered the sorafenib resistance. Overall, the collective findings highlight GINS1 functions in hepatocarcinogenesis and sorafenib resistance, and indicate its potential use of GINS1 in drug-resistant HCC.

Objective: To investigate the safety, efficacy, and prognostic factors of hepatic arterial infusion chemotherapy (HAIC) with raltitrexed and oxaliplatin post-transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC). Methods: Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited. The primary endpoint was overall survival (OS), and secondary endpoint was progression-free survival (PFS). The overall response rate (ORR) was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (v4.0). The OS and prognostic factors were analyzed using the Kaplan–Meier method, log-rank test, and Cox regression models. Results: Three (8.1%) patients achieved complete response, 17 (46.0%) patients achieved partial response, and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months, respectively. The common toxicities included grade 3–4 increased aspartate aminotransferase levels (8/37,21.6%), grade 1–2 hyperbilirubinemia (75.7%, 28/37), nonspecific abdominal pain and fever, and grade 2–3 thrombocytopenia (18.9%, 7/37); no patients developed grade 3–4 neutropenia. Univariate analysis showed that the tumor diameter (≤50 mm, p = 0.028), Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.012), hepatitis B virus DNA level (p = 0.033), and derived neutrophil-to-lymphocyte ratio (dNLR; derived neutrophils/leukocytes minus neutrophils) (p = 0.003) were predictive factors for prognosis. Multivariate analysis showed that patients with BCLC stage B disease (p = 0.029) and dNLR≤2 before therapy (p = 0.004) had better prognosis. Conclusions: HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC; in particular, those with BCLC stage B and dNLR≤2 have better prognosis. Keywords: Hepatocellular carcinoma, Transcatheter arterial chemoembolization (TACE), Hepatic arterial infusion chemotherapy (HAIC), Oxaliplatin, Raltitrexed

Abstract Background The technique for arterial infusion chemotherapy (HAIC) is not standardized which limits its widely application. The aim of this study was to evaluate the long-term functionality and complications of port-catheter system using percutaneous unilateral trans-femoral implantation with coil only fixed-catheter-tip method. Methods From January 2013 to January 2017, 205 consecutive patients (138 men; aged 28–88 years; mean, 59.1 ± 11.2 years) with unresectable malignant liver tumors underwent percutaneous implantation of side-hole infusion port-catheter into hepatic artery using coil only fixed-catheter-tip method via the unilateral femoral artery. Technical success, procedure time, duration of port functionality, and complications of port dysfunction were investigated. Results Implantation technical success was 98.5% and the procedure time was 59.1 ± 10.2 min. Predictable functionality of the port-catheter system at 6-, 12-, and 24 months were 97.5, 89.9, 70.5%, respectively. Complications of port irreversible dysfunction were hepatic artery obstruction (4.0%), catheter occlusion (3.5%), and catheter dislocation (0.5%). Median 5 HAIC cycles (range: 1–14 cycles) were received via port. Conclusion Percutaneous unilateral trans-femoral implantation of a side-hole port-catheter with coils only fixed-catheter-tip method is a simple and feasible interventional technique for HAIC which offers long-term functionality.

Shear-induced grain boundary migration at the atomic level is still not well understood. Here the authors combine in situ shear testing experiments and molecular dynamic simulations to reveal the atomistic mechanism of disconnection-mediated GB migration in different gold nanostructures.

In ruminants, the bacterial community in the gastrointestinal tract (GIT) has an essential role in healthy growth. Examining the bacterial composition in the GIT between growth-retarded and normal yaks could improve our understanding of the role of microorganisms in yaks with growth retardation. In this study, eight male yaks with growth retardation were used as the growth-retarded yak (GRY) group, and another eight male growth normal yaks (GNYs) with the same breed and age were used as the GNY group. We compared the bacterial community in the rumen, duodenum, jejunum, ileum, cecum, and colon between GRY and GNY groups based on the 16S ribosomal RNA gene sequencing. Alpha-diversity revealed that the Shannon index in the duodenum and ileum of the GNY group was higher (P < 0.05) than that of the GRY group. However, the opposite trend was found in the jejunum and cecum. The principal coordinates analysis (PCoA) showed that the bacterial structure in all segments of GIT differed from each other between two groups. In the rumen, the relative abundances of Ruminococcaceae NK4A214 group, Ruminococcaceae UCG-014, and Treponema 2 were higher (P < 0.05) in the GNY group as compared with the GRY group. However, the Christensenellaceae R-7 group exhibited an opposite trend. In the jejunum, compared with the GNY group, the unclassified Chitinophagaceae was enriched significantly (P < 0.05) in the GRY group. However, the unclassified Peptostreptococcaceae, Christensenellaceae R-7 group, and Lachnospiraceae NK3A20 group were enriched (P < 0.05) in the GNY group. In the ileum, the relative abundances of the Rikenellaceae RC9 gut group and Prevotellaceae UCG-004 were higher (P < 0.05) in the GNY group than those in the GRY group. In the cecum, the GNY group showed a higher (P < 0.05) relative abundance of Prevotellaceae UCG-003 as compared with the GRY group. In the colon, the relative abundances of Treponema 2 and unclassified Lachnospiraceae were slightly higher (0.05 < P < 0.10) in the GNY group than those in the GRY group. Overall, these results improve our knowledge about the bacterial composition in the GIT of growth-retarded and normal yaks, and regulating the bacterial community may be an effective solution to promote the compensatory growth of GRYs.

Background Yak (Bos grunniens) is an ancient bovine species on the Qinghai-Tibetan Plateau. Due to extremely harsh condition in the plateau, the growth retardation of yaks commonly exist, which can reduce the incomes of herdsman. The gastrointestinal barrier function plays a vital role in the absorption of nutrients and healthy growth. Functional deficiencies of the gastrointestinal barrier may be one of the contributors for yaks with growth retardation. Methods To this end, we compared the growth performance and gastrointestinal barrier function of growth-retarded (GRY) and normal yaks (GNY) based on average daily gain (ADG), serum parameters, tissue slice, real-time PCR, and western blotting, with eight yaks in each group. Results GRY exhibited lower (P

Purpose: Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC. Patients and Methods: In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAICFOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Results: Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). Conclusion: The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC. [ABSTRACT FROM AUTHOR]