Pelvic packing or endovascular interventions: Which should be given priority in managing hemodynamically unstable pelvic fractures? A systematic review and a meta-analysis.

Background: Pelvic fractures in trauma patients can be associated with substantial massive hemorrhage. Hemostasis interventions mainly consist of pelvic packing (PP) and endovascular intervention (EI), such as angiography-embolization (AE) and resuscitative endovascular balloon occlusion of the aorta (REBOA). Whether PP or EI should be prioritized for the management of hemodynamic unstable patients with pelvic fractures remains under debate. This meta-analysis aimed to establish the evidence-based recommendations for the management of hemodynamic unstable patients. Materials and methods: PubMed, CENTRAL, and EMBASE databases were searched for articles published from January 1, 2000 to January 31, 2023. Eligible studies, such as retrospective cohort studies, propensity score matching studies, prospective cohort studies, observational cohort studies, quasi-randomized clinical trials evaluating PP and EI (AE or REBOA) for the management of patients with hemodynamically unstable pelvic fractures, were included. Mean Difference (MD), relative risk (RR), and 95 % confidence intervals (CI) were calculated using fixed- or random-effects models depending on the heterogeneity of included trials. We compared the effectiveness of the two methods in terms of mortality, unstable fracture pattens, injury severity score (ISS), systolic blood pressure (SBP), lactate (LA), base deficiency (BE), hemoglobin preoperatively, blood transfusion requirement, the time to and of operation, complications. Results: Overall, 15 trials enrolling 1136 patients were analyzed, showing a total mortality rate of 28.4 % (323/1136). No effect of PP preference on the ISS (PP 36.4 ± 10.4 vs. EI 34.5 ± 12.7), SBP (PP 81.1 ± 24.3 mmHg vs. EI 94.2 ± 32.4 mmHg), LA (PP 4.66 ± 2.72 mmol/L vs. 4.85 ± 3.45 mmol/L), BE (PP 8.14 ± 5.64 mmol/L vs. 6.66 ± 5.68 mmol/L), and unstable fracture patterns (RR = 1.10, 95 % CI [0.63, 1.92]) was observed. PP application was associated with lower preoperative hemoglobin level (PP 8.11 ± 2.28 g/dL vs. EI 8.43 ± 2.43 g/dL, p < 0.05), more preoperative transfusion (MD = 2.53, 95 % CI [0.01, 5.06]), less postoperative transfusion within the first 24 h (MD = -1.09, 95 % CI [-1.96, -0.22]), shorter waiting time to intervention (MD = -0.93, 95 % CI [-1.54, -0.31]), and shorter operation time of intervention (MD = -0.41, 95 % CI [-0.52, -0.30]). PP had lower mortality rate owing to uncontrolled hemorrhage in the acute phase (RR = 0.41, 95 % CI [0.22, 0.79]). There was neither difference in mortality due to other complications (RR = 1.60, 95 % CI [0.79, 3.24]), nor in total mortality (RR = 0.92, 95%CI [0.49, 1.74]) (p > 0.05). Conclusions: PP showed advantages of reducing the amount of postoperative transfusion, shortening the time of waiting and operating, and decreasing mortality due to uncontrolled hemorrhage in the acute phase without raising the odds of mortality due to complications. PP, a reliable hemostatic method, should be prioritized for resuscitating most pelvic fractures with hemodynamically unstable, especially in case of bleeding from veins and fracture sites, as well as inadequate EI.

Directional Pumpless Transport of Biomolecules through Self-Propelled Nanodroplets on Patterned Heterostructures.

The surface patterning in natural systems has exhibited appreciable functional advantages for life activities, which serve as inspiration for the design of artificial counterparts to achieve functions such as directional liquid transport at the nanoscale. Here, we propose a patterned two-dimensional (2D) in-plane heterostructure with a triangle-shaped hexagonal boron nitride (hBN) track embedded in graphene nanosheets, which can achieve unidirectional and self-propelled transport of nanodroplets carrying various biomolecules such as DNA, RNA, and peptides. Our extensive MD simulations show that the wettability gradient on the patterned heterostructure can drive the motion of nanodroplet with an instantaneous acceleration, which also permits long-distance transport (>100 nm) at the microsecond time scale. The different behaviors of various types of biomolecules have been further studied systematically within the transporting nanodroplets. These findings suggest that these specially designed, patterned heterostructures have the potential for spontaneous, directional transport of important biomolecules, which might be useful in biosensing, drug delivery, and biomedical nanodevices.

In Situ Photoactivated Antibacterial and Antioxidant Composite Materials to Promote Bone Repair.

Trauma and tumor removal usually cause bone defects; in addition, the related postoperative infection also shall be carefully considered clinically. In this study, polylactic acid (PLLA) composite fibers containing Cerium oxide (CeO2) are first prepared by electrospinning technology. Then, the PLLA/CeO2@PDA/Ag composite materials are successfully prepared by reducing silver ion (Ag+) to nano-silver (AgNPs)  coating in situ and binding AgNPs to the materials surface by mussel structure liked polydopamine (PDA). In the materials, Ag+ can be slowly released in simulated body fluids. Based on the photothermal performance of AgNPs, the photothermal conversion efficiency of the materials is 21%, under NIR 808 nm illumination. The effective photothermal conversion can help materials fighting with E. coli and S. aureus in 3 h, with an antibacterial rate of 100%. Additionally, the sustained Ag+ release contributes to the antibacterial in long term. Meanwhile, the materials can mimic the bio-behavior of superoxide dismutase and catalase in decreasing the singlet oxygen level and removing the excess reactive oxygen species. Furthermore, the materials are beneficial for cell proliferation and osteogenic differentiation in vitro. In this study, a promising bone-regenerated material with high photothermal conversion efficiency and antibacterial and anti-oxidation properties, is successfully constructed.

The relationship between imaging features, therapeutic response, and overall survival in pediatric diffuse intrinsic pontine glioma.

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.

Inhibition of DEF-p65 Interactions as a Potential Avenue to Suppress Tumor Growth in Pancreatic Cancer.

The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.

Enhancing low-concentration cell detection in single entity electrochemical systems through forced convection.

This study advances the detection of bacteria at low concentrations in single-entity electrochemistry (SEE) systems by integrating forced convection. Our results show that forced convection significantly improves the mass transfer rate of electrolyte, with the mass transfer coefficient demonstrating a proportional relationship to the flow rate to the power of 1.37. Notably, while the collision frequency of E. coli initially increases with the flow rate, a subsequent decrease is observed at higher rates. This pattern is attributed to the mechanics of cell collision under forced convection. Specifically, while forced convection propels cells towards the ultra-microelectrode (UME), it does not aid in their penetration through the boundary layer, leading to cells being driven away from the UME at higher flow rates. This hypothesis is supported by the statistical analysis of collision data, including signal heights and rise times. By optimizing the flow rate to 2 mL/min, we achieved enhanced detection of E. coli in concentrations ranging from 0.9 × 107 to 5.0 × 107 cells/mL. This approach significantly increased collision frequency by elevating the mass transfer of cells, with the mass transfer coefficient rising from 0.1 × 10-5 m/s to 0.9 × 10-5 m/s. It provides a viable solution to the challenges of detecting bacteria at low concentrations in SEE systems.

Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

Sludge deep dewatering by liquefied dimethyl ether: selection of operating conditions based on response surface methodology.

Sludge is an inevitable by-product of the sewage treatment process and its high moisture content poses significant challenges for its treatment and disposal. This study focuses on the technology of sludge deep dewatering using liquefied dimethyl ether (DME) and explores the relationship between operating parameters (DME/sludge ratio, extraction time and stirring speed) and the water content of the sludge after deep dewatering. After deep dewatering, the sludge's lower heating value (LHV) was significantly increased. The dehydrated filtrate is highly biodegradable and could be treated together with sewage. Based on the response surface method of central composite design, a second-order regression model of the above three variables and sludge water content as the response was established. Finally, the operating conditions diagram was drawn by target water content (36.96 wt.%) which meets the requirement of self-sustained incineration and model equation. This study provides a valuable perspective on sludge drying and fuelisation.

Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages.

Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC.

ROF-2 as an Aggregation-Induced Emission (AIE) Probe for Multi-Target Amyloid Detection and Screening of Amyloid Inhibitors.

Misfolding and aggregation of amyloid peptides into ß-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid-ß, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid-induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE-based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.

Deep Generative Adversarial Reinforcement Learning for Semi-Supervised Segmentation of Low-Contrast and Small Objects in Medical Images.

Deep reinforcement learning (DRL) has demonstrated impressive performance in medical image segmentation, particularly for low-contrast and small medical objects. However, current DRL-based segmentation methods face limitations due to the optimization of error propagation in two separate stages and the need for a significant amount of labeled data. In this paper, we propose a novel deep generative adversarial reinforcement learning (DGARL) approach that, for the first time, enables end-to-end semi-supervised medical image segmentation in the DRL domain. DGARL ingeniously establishes a pipeline that integrates DRL and generative adversarial networks (GANs) to optimize both detection and segmentation tasks holistically while mutually enhancing each other. Specifically, DGARL introduces two innovative components to facilitate this integration in semi-supervised settings. First, a task-joint GAN with two discriminators links the detection results to the GAN's segmentation performance evaluation, allowing simultaneous joint evaluation and feedback. This ensures that DRL and GAN can be directly optimized based on each other's results. Second, a bidirectional exploration DRL integrates backward exploration and forward exploration to ensure the DRL agent explores the correct direction when forward exploration is disabled due to lack of explicit rewards. This mitigates the issue of unlabeled data being unable to provide rewards and rendering DRL unexplorable. Comprehensive experiments on three generalization datasets, comprising a total of 640 patients, demonstrate that our novel DGARL achieves 85.02% Dice and improves at least 1.91% for brain tumors, achieves 73.18% Dice and improves at least 4.28% for liver tumors, and achieves 70.85% Dice and improves at least 2.73% for pancreas compared to the ten most recent advanced methods, our results attest to the superiority of DGARL. Code is available at GitHub.

Elucidation of the molecular mechanism of the breakage-fusion-bridge (BFB) cycle using a CRISPR-dCas9 cellular model.

Chromosome instability (CIN) is frequently observed in many tumors. The breakage-fusion-bridge (BFB) cycle has been proposed to be one of the main drivers of CIN during tumorigenesis and tumor evolution. However, the detailed mechanisms for the individual steps of the BFB cycle warrants further investigation. Here, we demonstrated that a nuclease-dead Cas9 (dCas9) coupled with a telomere-specific single-guide RNA (sgTelo) can be used to model the BFB cycle. First, we showed that targeting dCas9 to telomeres using sgTelo impeded DNA replication at telomeres and induced a pronounced increase of replication stress and DNA damage. Using Single-Molecule Telomere Assay via Optical Mapping (SMTA-OM), we investigated the genome-wide features of telomeres in the dCas9/sgTelo cells and observed a dramatic increase of chromosome end fusions, including fusion/ITS+ and fusion/ITS-.Consistently, we also observed an increase in the formation of dicentric chromosomes, anaphase bridges, and intercellular telomeric chromosome bridges (ITCBs). Utilizing the dCas9/sgTelo system, we uncovered many novel molecular and structural features of the ITCB and demonstrated that multiple DNA repair pathways are implicated in the formation of ITCBs. Our studies shed new light on the molecular mechanisms of the BFB cycle, which will advance our understanding of tumorigenesis, tumor evolution, and drug resistance.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P<0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. Results: The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. Conclusions: The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

Quantitative evaluation of meniscus injury using synthetic magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) can diagnose meniscal lesions anatomically, while quantitative MRI can reflect the changes of meniscal histology and biochemical structure. Our study aims to explore the association between the measurement values obtained from synthetic magnetic resonance imaging (SyMRI) and Stoller grades. Additionally, we aim to assess the diagnostic accuracy of SyMRI in determining the extent of meniscus injury. This potential accuracy could contribute to minimizing unnecessary invasive examinations and providing guidance for clinical treatment. METHODS: Total of 60 (n=60) patients requiring knee arthroscopic surgery and 20 (n=20) healthy subjects were collected from July 2022 to November 2022. All subjects underwent conventional MRI and SyMRI. Manual measurements of the T1, T2 and proton density (PD) values were conducted for both normal menisci and the most severely affected position of injured menisci. These measurements corresponded to the Stoller grade of meniscus injuries observed in the conventional MRI. All patients and healthy subjects were divided into normal group, degeneration group and torn group according to the Stoller grade on conventional MRI. One-way analysis of variance (ANOVA) was employed to compare the T1, T2 and PD values of the meniscus among 3 groups. The accuracy of SyMRI in diagnosing meniscus injury was assessed by comparing the findings with arthroscopic observations. The diagnostic efficiency of meniscus degeneration and tear between conventional MRI and SyMRI were analyzed using McNemar test. Furthermore, a receiver operating characteristic curve (ROC curve) was constructed and the area under the curve (AUC) was utilized for evaluation. RESULTS: According to the measurements of SyMRI, there was no statistical difference of T1 value or PD value measured by SyMRI among the normal group, degeneration group and torn group, while the difference of T2 value was statistically significant among 3 groups (P=0.001). The arthroscopic findings showed that 11 patients were meniscal degeneration and 49 patients were meniscal tears. The arthroscopic findings were used as the gold standard, and the difference of T1 and PD values among the 3 groups was not statistically significant, while the difference of T2 values (32.81±2.51 of normal group, 44.85±3.98 of degeneration group and 54.42±3.82 of torn group) was statistically significant (P=0.001). When the threshold of T2 value was 51.67 (ms), the maximum Yoden index was 0.787 and the AUC value was 0.934. CONCLUSIONS: The measurement values derived from SyMRI could reflect the Stoller grade, illustrating that SyMRI has good consistency with conventional MRI. Moreover, the notable consistency observed between SyMRI and arthroscopy suggests a potential role for SyMRI in guiding clinical diagnoses.

Individualized nutritional intervention improves the nutritional status of liver cancer patients after transcatheter arterial chemoembolization.

INTRODUCTION: to explore the effect of individualized nutritional intervention on the nutritional status of patients with liver cancer after transcatheter arterial chemoembolization (TACE). METHODS: 56 patients who underwent TACE in our hospital from March 2022 to March 2023 were selected as the study subjects. The patients were randomly divided into a control group (28 cases) and an intervention group (28 cases). The control group received routine dietary intervention, while the intervention group received individualized nutritional intervention. We analyzed the body mass index (BMI), nutritional risk screening 2002 (NRS 2002), nutritional status, liver function status, and incidence of complications in two groups of patients before TACE, 3 days after TACE, and 1 month after TACE. RESULTS: on the third day after TACE, the nutritional related indicators of both groups of patients showed a significantly decrease compared to those before TACE (p < 0.05), while the majority of liver function indicators significantly increased (p < 0.05). Compared with those at 3 days after TACE, the nutritional status of the intervention group patients significantly improved (p < 0.05) and liver function indicators significantly decreased (p < 0.05) 1 month after TACE. 1 month after TACE, all nutritional indicators in the intervention group were significantly higher than those in the control group (p < 0.05), and AST was significantly lower than that in the control group (p < 0.05). The incidence of gastrointestinal complications and electrolyte disorders in the intervention group were significantly lower than that in the control group (p < 0.05). Conclusion Individualized nutritional intervention can effectively improve nutritional status, improve liver function, and reduce the incidence of postoperative complications in liver cancer patients after TACE. It was worth promoting.

Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Anti-osteoporosis activity of casticin in ovariectomized rats.

Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored. Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators. Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro. Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.

Structural Evolution of Bacterial Polyphosphate Degradation Enzyme for Phosphorus Cycling.

Living organisms ranging from bacteria to animals have developed their own ways to accumulate and store phosphate during evolution, in particular as the polyphosphate (polyP) granules in bacteria. Degradation of polyP into phosphate is involved in phosphorus cycling, and exopolyphosphatase (PPX) is the key enzyme for polyP degradation in bacteria. Thus, understanding the structure basis of PPX is crucial to reveal the polyP degradation mechanism. Here, it is found that PPX structure varies in the length of ɑ-helical interdomain linker (ɑ-linker) across various bacteria, which is negatively correlated with their enzymatic activity and thermostability - those with shorter ɑ-linkers demonstrate higher polyP degradation ability. Moreover, the artificial DrPPX mutants with shorter ɑ-linker tend to have more compact pockets for polyP binding and stronger subunit interactions, as well as higher enzymatic efficiency (kcat/Km) than that of DrPPX wild type. In Deinococcus-Thermus, the PPXs from thermophilic species possess a shorter ɑ-linker and retain their catalytic ability at high temperatures (70 °C), which may facilitate the thermophilic species to utilize polyP in high-temperature environments. These findings provide insights into the interdomain linker length-dependent evolution of PPXs, which shed light on enzymatic adaption for phosphorus cycling during natural evolution and rational design of enzyme.

XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial.

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.