The damage mechanism in copper studied using in situ TEM nanoindentation.

Copper (Cu) has a soft-plastic nature, which makes it susceptible to damages from scratching or abrasive machining, such as lapping and polishing. It is a challenge to control these damages as the damage mechanism is elusive. Nonetheless, controlling damages is essential, especially on the atomic surfaces of Cu. To interpret the damage mechanism, in situ transmission electron microscopy (TEM) nanoindentation was performed using a cube-corner indenter with a radius of 57 nm at a loading speed of 5 nm s-1. Experimental results showed that damages originate from dislocations, evolve to stack faults, and then form broken crystallites. When the indentation depth was 45 nm at a load of 20 µN, damages comprised dislocations and stacking faults. After increasing the depth to 67 nm and load to 30 µN, the formation of broken crystallites initiated; and the critical depth was 67 nm. To validate the damage mechanism, fixed-abrasive lapping, mechanical polishing, and chemical mechanical polishing (CMP) were conducted. Firstly, a novel green CMP slurry containing silica, hydrogen peroxide, and aspartic acid was developed. After CMP, a surface roughness Ra of 0.2 nm was achieved with a scanning area of 50 µm × 50 µm; and the thickness of the damaged layer was 3.1 nm, which included a few micro-stacking faults. Lapping and mechanical polishing were carried out using a silicon carbide plate and cerium slurry, with surface roughness Ra values of 16.42 and 1.74 nm, respectively. The damaged layer of the former with a thickness of 300 nm comprised broken crystallites, dislocations, and stacking faults and that of the latter with a thickness of 33 nm involved several stacking faults. This verifies that the damage mechanism derived from in situ TEM nanoindentation is in agreement with lapping and polishing. These outcomes propose new insights into understanding the origin of damages and controlling them, as well as obtaining atomic surfaces using a novel green CMP technique for soft-plastic metals.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

Nomogram for predicting moderate-to-severe sleep-disordered breathing in patients with acute ischaemic stroke: a retrospective cohort study.

OBJECTIVES: Moderate-to-severe sleep-disordered breathing (SDB) is prevalent in patients with acute ischaemic stroke (AIS) and is associated with an increased risk of unfavourable prognosis. We aimed to develop and validate a reliable scoring system for the early screening of moderate-to-severe SDB in patients with AIS, with the objective of improving the management of those patients at risk. STUDY DESIGN: We developed and validated a nomogram model based on univariate and multivariate logistic analyses to identify moderate-to-severe SDB in AIS patients. Moderate-to-severe SDB was defined as an apnoea-hypopnoea index (AHI) ≥15. To evaluate the effectiveness of our nomogram, we conducted a comparison with the STOP-Bang questionnaire by analysing the area under the receiver operating characteristic curve. SETTING: Large stroke centre in northern Shanghai serving over 4000 inpatients, 100 000 outpatients and emergency visits annually. PARTICIPANTS: We consecutively enrolled 116 patients with AIS from the Shanghai Tenth People's Hospital. RESULTS: Five variables were independently associated with moderate-to-severe SDB in AIS patients: National Institutes of Health Stroke Scale score (OR=1.20; 95% CI 0.98 to 1.47), neck circumference (OR=1.50; 95% CI 1.16 to 1.95), presence of wake-up stroke (OR=21.91; 95% CI 3.08 to 156.05), neuron-specific enolase level (OR=1.27; 95% CI 1.05 to 1.53) and presence of brainstem infarction (OR=4.21; 95% CI 1.23 to 14.40). We developed a nomogram model comprising these five variables. The C-index was 0.872, indicated an optimal agreement between the observed and predicted SDB patients. CONCLUSIONS: Our nomogram offers a practical approach for early detection of moderate-to-severe SDB in AIS patients. This tool enables individualised assessment and management, potentially leading to favourable outcomes.

High titer production of gastrodin enabled by systematic refactoring of yeast genome and an antisense-transcriptional regulation toolkit.

Gastrodin, a phenolic glycoside, is a prominent component of Gastrodia elata, which is renowned for its sedative, hypnotic, anticonvulsant, and neuroprotective activities. Engineering heterologous production of plant natural products in microbial host represents a safe, cost-effective, and scalable alternative to plant extraction. Here, we present the construction of an engineered Yarrowia lipolytica yeast that achieves a high-titer production of gastrodin. We systematically refactored the yeast genome by enhancing the flux of the shikimate pathway and optimizing the glucosyl transfer system. We introduced more than five dozen of genetic modifications onto the yeast genome, including enzyme screening, alleviation of rate-limiting steps, promoter selection, genomic integration site optimization, downregulation of competing pathways, and elimination of gastrodin degradation. Meanwhile, we developed a Copper-induced Antisense-Transcriptional Regulation (CATR) tool. The developed CATR toolkit achieved dynamic repression and activation of violacein synthesis through the addition of copper in Y. lipolytica. This strategy was further used to dynamically regulate the pyruvate kinase node to effectively redirect glycolytic flux towards the shikimate pathway while maintaining cell growth at proper rate. Taken together, these efforts resulted in 9477.1 mg/L of gastrodin in shaking flaks and 13.4 g/L of gastrodin with a yield of 0.149 g/g glucose in a 5-L bioreactor, highlighting the potential for large-scale and sustainable production of gastrodin from microbial fermentation.

Enhanced fatty acid storage combined with the multi-factor optimization of fermentation for high-level production of docosahexaenoic acid in Schizochytrium sp.

Schizochytrium sp. hasreceived much attention for itsability to synthesize and accumulate high-level docosahexaenoic acid (DHA), which can reach nearly 40 % of total fatty acids. In this study, the titer of DHA in Schizochytrium sp. was successfully improved by enhancing DHA storage through overexpressing the diacylglycerol acyltransferase (ScDGAT2C) gene, as well as optimizing the supply of precursors and cofactors required for DHA synthesis by response surface methodology. Notably, malic acid, citric acid, and biotin showed synergistic and time-dependent effects on DHA accumulation. The maximum lipid and DHA titers of the engineered Schizochytrium sp. strain reached 84.28 ± 1.02 g/L and 42.23 ± 0.69 g/L, respectively, with the optimal concentration combination (1.62 g/L malic acid + 0.37 g/L citric acid + 8.28 mg/L biotin) were added 48 h after inoculation. This study provides an effective strategy for improving lipid and DHA production in Schizochytrium sp.

Environmental and dietary exposure to 24 polycyclic aromatic hydrocarbons in a typical Chinese coking plant.

Polycyclic aromatic hydrocarbons (PAHs), known for their health risks, are prevalent in the environment, with the coking industry being a major source of their emissions. To bridge the knowledge gap concerning the relationship between environmental and dietary PAH exposure, we explore this complex interplay by investigating the dietary exposure characteristics of 24 PAHs within a typical Chinese coking plant and their association with environmental pollution. Our research revealed Nap and Fle as primary dietary contaminants, emphasizing the significant influence of soil and atmospheric pollution on PAH exposure. We subjected our data to non-metric multidimensional scaling (NMDS), Spearman correlation analysis, Lasso regression, and Weighted Quantile Sum (WQS) regression to delve into this multifaceted phenomenon. NMDS reveals that dietary PAH exposure, especially within the high molecular weight (HMW) group, is common both within and around the coking plant. This suggests that meals prepared within the plant may be contaminated, posing health risks to coking plant workers. Furthermore, our assessment of dietary exposure risk highlights Nap and Fle as the primary dietary contaminants, with BaP and DahA raising concerns due to their higher carcinogenic potential. Our findings indicate that dietary exposure often exceeds acceptable limits, particularly for coking plant workers. Correlation analyses uncover the dominant roles of soil and atmospheric pollution in shaping dietary PAH exposure. Soil contamination significantly impacts specific PAHs, while atmospheric pollution contributes to others. Additionally, WQS regression emphasizes the substantial influence of soil and drinking water on dietary PAHs. In summary, our study sheds light on the dietary exposure characteristics of PAHs in a typical Chinese coking plant and their intricate interplay with environmental factors. These findings underscore the need for comprehensive strategies to mitigate PAH exposure so as to safeguard both human health and the environment in affected regions.

Sequencing and Analysis of the Complete Mitochondrial Genome of Lentipes ikeae.

We sequenced and analyzed the complete mitochondrial genome of Lentipes ikeae and explored the phylogenetic relationships among Sicydiinae based on mitochondrial genome sequences. The complete mitochondrial genome sequence of L. ikeae was determined using the Illumina HiSeq X Ten sequencing platform, and the gene structural characteristics and base composition were analyzed. Based on the mitochondrial genome sequences of 28 Sicydiinae species published in GenBank and mitochondrial protein-coding genes (PCGs), Acanthogobius flavimanus (Gobionellinae) was selected as an outgroup to construct phylogenetic trees of Sicydiinae using the maximum likelihood and Bayesian inference methods. The mitochondrial genome of L. ikeae (GenBank number: OP764680) has a total length of 16,498 bp and encodes 13 PCGs, 22 transfer RNA genes, two ribosomal RNA genes, and a D-loop (control) region. Gene rearrangement is not observed. The mitochondrial genome of L. ikeae exhibits an AT preference, with AT skew > 0 and GC skew < 0 across the entire genome. The phylogenetic relationships of Sicydiinae based on 13 mitochondrial PCG sequences are Sicydium + (Stiphodon + (Sicyopus + Lentipes)) + Sicyopterus, indicating that Sicydium, Sicyopterus, Lentipes, and Stiphodon are all monophyletic groups.

[Nonlinear Variations in PM2. 5 Concentration in the Three Major Urban Agglomerations in China].

ITA and Beast methods were used to quantitatively analyze the nonlinear process of a PM2.5 concentration time series based on the PM2.5 concentration data of the three major urban agglomerations in China. The results showed that： ① the degree of the PM2.5 pollution in the three major urban agglomerations had decreased， and the high-concentration areas had noticeably shrunk. The degree of spatial polarization of PM2.5 concentration was reduced， and the spatial difference was narrowed. The PM2.5 concentration in most areas showed downward trends， but the degree of change was not the same. Compared with the YRD and PRD， the concentration of PM2.5 in the BTH was still at a relatively high level. ② The concentration of PM2.5 in the three major urban agglomerations had seasonal variation characteristics that were high in winter and spring and low in summer and autumn. There were obvious differences in PM2.5 concentration between winter and summer， and the convergence of PM2.5 concentration in summer was greater than that in winter. Areas with high PM2.5 concentration also had obvious downward trends， but the downward trends of PM2.5 concentration in the PRD were not obvious compared with those in the YRD and BTH. ③ The PM2.5 concentration time series of the three major urban agglomerations all had significant downward trends： Beijing-Tianjin-Hebei （BTH） > the Yangtze River Delta （YRD） > the Pearl River Delta （PRD）. The PM2.5 concentration had the largest downward trends in winter. The higher the PM2.5 pollution level， the greater the downward trends. ④ The trend component of the PM2.5 concentration time series in the BTH had two change points， and there was one change point in the seasonal component. The trend and seasonal components of the PM2.5 concentration time series in the YRD had no change point. There was no change point in the seasonal component but one change point in the trend component of the PM2.5 concentration time series in the PRD. These results can provide scientific references for regional air pollution control.

Dataset on sinusoidally stiffened 3D printed steel plated structures.

The paper reports a series of experimental and numerical data of destructive stub column tests on additively manufactured steel parts stiffened by surface sinusoidal wave patterns. The specimens were made in 316L stainless steel and manufactured by selective laser melting (SLM). The experimental tests covered five tensile coupon tests, fourteen square hollow section (SHS) stub column tests and measurements of geometric imperfections of the stub columns. Numerical models incorporating the measured material and geometric properties were developed and analysed via GMNIA approach. The validity of the numerical models is demonstrated by their accurate replications of the load-end shortening responses of the tested specimens. The reported dataset will contribute to the stability design and characterisation of thin-walled steel plated structures with advanced stiffening patterns.

Research on the impact of China's reform to delegate power, streamline administration, and optimize government services on the technology innovation efficiency of the pharmaceutical manufacturing industry.

Objective: The government has recently implemented reforms aimed at delegating power, streamlining administration, and optimizing government services. This reform has eliminated barriers that impede the growth of various industries, thereby unleashing innovative potential. Additionally, there have been several medical policies, including changes to medical insurance and centralized volume-based procurement. China's pharmaceutical market has undergone significant changes, leading to increased demands for innovation technology efficiency in pharmaceutical manufacturing. Methods: The three-stage BCC theory was employed to assess the effectiveness of technology innovation in the industry under this reform. Calculate precise comprehensive technical efficiency values, pure technical efficiency values, and scale efficiency values for technological innovation in the pharmaceutical industry across 30 provinces from 2018 to 2020, after removing environmental factors. Results: In 2020, Jiangsu and Shandong and nine other provinces reached the comprehensive technical efficiency frontier surface, joining Tianjin, Zhejiang, and Guangdong provinces. However, Gansu, Qinghai, Ningxia, and Xinjiang still need to catch up due to their smaller industrial scale and lack of technology. Discussion: To ensure the effectiveness of reforms, it is crucial to fully consider provincial differences. Articulating national and provincial policies is necessary to allow efficient provinces to continue and allocate resources toward less efficient provinces to improve overall efficiency.

Probabilistic risk assessment of microplastics on aquatic biota in coastal sediments.

As an emerging form of pollution, microplastic contamination of the coastal ecosystems is one of the world's most pressing environmental concerns. Coastal sediments have been polluted to varying degrees by microplastics, and their ubiquitous presence in sediments poses a threat to marine organisms. However, there is currently no ecological risk assessment of microplastics on aquatic biota in sediments. This study, for the first time, established a new procedure to evaluate the toxicity of microplastics on aquatic biota in sediments, based on the probabilistic risk assessment (PRA) concept. The choice of Zhelin Bay as the case study site was based on its severe pollution status. The average content of microplastics in the sediments of Zhelin Bay was 2054.17 items kg-1 dry weight, and these microplastics consisted of 46 different species. Microplastics in sediments exist in five different forms, with the film form being the main composition, and the majority of microplastics have particle sizes ranging from 100 to 500 µm. Correlation analysis (CA) reveals significant negative correlations between microplastic abundance, and Al2O3 and SiO2. The toxicity of microplastics, based on the PRA concept, suggests that Zhelin Bay surface sediments had a low probability (3.43%) of toxic effects on aquatic biota.

Efficient Catalytic Oxidation of Ethylene at 0 °C on an in Situ Carbon Modified Pt Catalyst Supported on SBA-15.

The design of efficient catalysts for catalytic ethylene (C2H4) oxidation is of crucial importance for extending the shelf life of fruits and vegetables. Herein, a carbon modified SBA-15 supported Pt catalyst (Pt/CSBA-15) was prepared in situ by a facile solid phase grinding-infiltration-inert atmosphere calcination method. Characterization results reveal that in the Pt/CSBA-15 catalysts thin carbon layers are successfully formed in the hexagonal pores of SBA-15. Additionally, Pt particles are well dispersed in the channels of SBA-15, and Pt/CSBA-15 has a smaller Pt particle size than the catalyst without carbon modification (i.e., Pt/SBA-15). O2 is more feasibly adsorbed and activated on small-sized Pt particles, and in situ formed carbon species enhance the hydrophobicity of catalysts. As a result, both 3Pt/CSBA-15 and 5Pt/CSBA-15 are able to maintain 100% conversion of 50 ppm of C2H4 for more than 7 h at 0 °C. 3Pt/CSBA-15 even achieves 81.5% C2H4 conversion and 71.6% CO2 yield after 20 h, exhibiting much more prominent catalytic performances than 3Pt/SBA-15. DFT calculations and in situ FTIR measurements confirm that small-sized Pt particles possess strong O2 affinity to promote O2 adsorption, and in situ formed hydrophobic carbon layers efficiently suppress competitive H2O adsorption. Such a unique one-step catalyst preparation method for regulating the size of metal particles and the hydrophobicity of catalysts can be perfectly utilized to develop simple and efficient hydrophobic catalysts applied in low-temperature oxidation of C2H4.

A toolbox for genetic manipulation in intestinal Clostridium symbiosum.

Gut microbes are closely related with human health, but remain much to learn. Clostridium symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal tumors. However, the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth studies. Here, we obtained the complete genome sequence of C. symbiosum ATCC 14940, a representative strain of C. symbiosum. On this basis, we further developed a series of genetic manipulation methods for this bacterium. Firstly, following the identification of a functional replicon pBP1 in C. symbiosum ATCC 14940, a highly efficient conjugative DNA transfer method was established, enabling the rapid introduction of exogenous plasmids into cells. Next, we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium, reaching over 60 % repression for most of the chosen genes as well as efficient deletion (>90 %) of three target genes. Finally, this toolbox was used for the identification of crucial functional genes, involving growth, synthesis of important metabolites, and virulence of C. symbiosum ATCC 14940. Our work has effectively established and optimized genome editing methods in intestinal C. symbiosum, thereby providing strong support for further basic and application research in this bacterium.

Exploring the efficacious constituents and underlying mechanisms of sini decoction for sepsis treatment through network pharmacology and multi-omics.

BACKGROUND: Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients. However, its underlying mechanisms remain unclear, and therapeutic effects may vary among individuals. PURPOSE: Through a comprehensive and systematic network pharmacology analysis, the purpose of this study is to investigate the therapeutic mechanisms of SND in treating sepsis. METHODS: An analysis of WGCNA identified CX3CR1 as a key gene influencing sepsis prognosis. A drug-active component-target network for SND was created using the traditional Chinese medicine systems pharmacology (TCMSP) database and Cytoscape software. Shared targets between SND and CX3CR1 high-expression gene modules were found through the GEO database. Gene module functionality was analyzed using GO, KEGG, GSEA, and GSVA. Unsupervised clustering of sepsis patients was performed based on the ferroptosis gene set, and immune cell interactions and mechanisms were explored using CIBERSORT, single-cell sequencing, and intercellular communication analysis. RESULTS: This study demonstrates that high expression of CX3CR1 improves survival rates in sepsis patients and is associated with immune cell signaling pathways. SND contains 116 active components involved in oxidative stress and lipid metabolism pathways. HMOX1, a co-expressed gene in SND and CX3CR1 high-expression gene module, plays a crucial role in sepsis survival. Unsupervised clustering analysis classified sepsis patients into three clusters based on the ferroptosis gene set, revealing differences in immune cell expression and involvement in heme metabolism pathways. Notably, intercellular interactions among immune cells primarily occur through paracrine and autocrine mechanisms in MIF, GALECTIN, and IL16 signaling pathways, modulating the immune-inflammatory microenvironment in sepsis. CONCLUSIONS: This study identifies CX3CR1 as a crucial molecule impacting sepsis prognosis through WGCNA analysis. It reveals that SND's active component, quercetin and kaempferol, target HMOX1 via related pathways to regulate heme metabolism, reduce inflammation, inhibit ferroptosis, and improve immune function, ultimately improving sepsis prognosis. These findings offer a solid pharmacological foundation and potential therapeutic targets for SND in treating sepsis.

Effect of azilsartan on myocardial remodeling after acute myocardial infarction.

PURPOSE: To investigate the effect of azilsartan on myocardial remodeling after acute myocardial infarction (AMI). METHODS: A total of 200 AMI patients under percutaneous coronary intervention (PCI) were selected from the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from Jan 2021 to Dec 2021. The subjects were randomly divided to take either azilsartan or benazepril. Serum C1q tumor necrosis factor-associated protein 1 (CTRP1) levels were detected in all subjects after admission, and the indices of left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) were measured by using echocardiography. At the follow-up of 6 months and 1 year after PCI, the differences in CTRP1 and echocardiogram indices between the two groups were compared, and the influencing factors of myocardial remodeling after acute myocardial infarction were analyzed. RESULTS: The levels of LVEDV and CTRP1 in all subjects at 6 months and 1 year after PCI were lower than those before discharge, and the LVEDV in the azilsartan group at 6 months and 1 year after PCI was lower than that in the benazepril group. An improvement in myocardial remodeling was obviously observed within 6 months after PCI, but the effect declined over time. CONCLUSIONS: Azilsartan can improve myocardial remodeling after acute myocardial infarction. CTRP1 may become an effective target for the prevention and treatment of myocardial remodeling after acute myocardial infarction.

Supraglottic Jet Oxygenation and Ventilation to Minimize Hypoxia in Patients Receiving Flexible Bronchoscopy Under Deep Sedation: A 3-Arm Randomized Controlled Trial.

BACKGROUND: Hypoxia often occurs due to shared airway and anesthetic sedation-induced hypoventilation in patients receiving flexible bronchoscopy (FB) under deep sedation. Previous evidence has shown that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) reduces the incidence of hypoxia during FB. This study aimed to investigate the extent to which SJOV via WNJ could decrease the incidence of hypoxia in patients under deep sedation as compared to oxygen supplementation via WNJ alone or nasal catheter (NC) for oxygen supplementation during FB. METHODS: This was a single-center 3-arm randomized controlled trial (RCT). Adult patients scheduled to undergo FB were randomly assigned to 3 groups: NC (oxygen supplementation via NC), low-pressure low-flow (LPLF) (low-pressure oxygen supplementation via WNJ alone), or SJOV (high-pressure oxygen supplementation via WNJ). The primary outcome was hypoxia (defined as peripheral saturation of oxygen [Sp o2 ] <90% lasting more than 5 seconds) during FB. Secondary outcomes included subclinical respiratory depression or severe hypoxia, and rescue interventions specifically performed for hypoxia treatment. Other evaluated outcomes were sore throat, xerostomia, nasal bleeding, and SJOV-related barotraumatic events. RESULTS: One hundred and thirty-two randomized patients were included in 3 interventions (n = 44 in each), and all were included in the final analysis under intention to treat. Hypoxia occurred in 4 of 44 patients (9.1%) allocated to SJOV, compared to 38 of 44 patients (86%) allocated to NC, with a relative risk (RR) for hypoxia, 0.11; 98% confidence interval (CI), 0.02-0.51; P < .001; or to 27 of 44 patients (61%) allocated to LPLF, with RR for hypoxia, 0.15; 95% CI, 0.04-0.61; P < .001, respectively. The percentage of subclinical respiratory depression was also significantly diminished in patients with SJOV (39%) compared with patients with NC (100%) or patients with LPLF (96%), both P < .001. In SJOV, no severe hypoxia event occurred. More remedial interventions for hypoxia were needed in the patients with NC. Higher risk of xerostomia was observed in patients with SJOV. No severe adverse event was observed throughout the study. CONCLUSIONS: SJOV via WNJ effectively reduces the incidence of hypoxia during FB under deep sedation.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Cannula-Associated Deep Vein Thrombosis After Venovenous Extracorporeal Membrane Oxygenation in Patients with and Without Systemic Anticoagulation.

OBJECTIVE: To identify and compare the rates of cannula-associated deep vein thrombosis (CaDVT) in patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) who receive systemic anticoagulation (AC) and those who do not receive AC. DESIGN: Retrospective observational study. SETTING: Tertiary academic medical center. PARTICIPANTS: Consecutive patients who successfully have been decannulated from VV-ECMO for treatment of refractory acute respiratory distress syndrome between 2017 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After decannulation of ECMO, a duplex sonograph was performed on the cannulation sites to determine the incidence and characteristics of cannula-related thrombosis. Thrombosis was classified as occlusive or nearly occlusive. Ninety-four of 161 patients were weaned from VV-ECMO. Nineteen patients who were placed on VV-ECMO due to COVID-19 were excluded. Twenty-seven of 52 patients (52%) who did not receive AC were identified to have thrombus. Twelve of 23 patients (52%) who received AC were identified to have thrombus. Patients who received AC required more blood products during the ECMO run and required longer support on VV-ECMO. CONCLUSION: This study showed a high incidence of cannula-related venous thrombosis after VV-ECMO decannulation. Surprisingly, the incidence of CaDVT in anticoagulation-free patients was the same as in patients requiring anticoagulation. Anticoagulated patients required longer support on VV-ECMO and required more transfusions. Routine post-decannulation screening for DVT is recommended due to the high incidence of CaDVT.