Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 µg/g) were significantly greater compared to the LF group (0.02 ± 0.01 µg/g, P < 0.001) and GD group (0.37 ± 0.11 µg/g, P < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 µg/g) compared to the LF group (0.01 ± 0.00 µg/g, P < 0.001) and GD group (0.06 ± 0.02 µg/g, P = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group. Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.

Effect of biofeedback intervention on neurological characteristics of children with attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate the effects of biofeedback intervention on the neurological characteristics of children with attention deficit hyperactivity disorder (ADHD). METHODS: 150 children aged 6-12 years with ADHD were divided into two groups according to the treatment method. The atomoxetine group received atomoxetine drug treatment, and the combined treatment group received EEG biofeedback therapy. Continuous performance test (CPT), SNAP-IV and WFIRS-P were used to assess attention and behavior, and functional magnetic resonance imaging (fMRI) was used to observe changes in brain activity. RESULTS: The response time, error times, error response rate and attention fluctuation index of CPT in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.05), and the correct response rate was higher than that in the atomoxetine group (p < 0.05). After intervention, SNAP-IV and WFIRS-P scores in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.001). fMRI results showed that the activity of the prefrontal, parietal, amygdala and hippocampus in the combined treatment group was significantly higher than that in the atomoxetine group (p < 0.001). CONCLUSION: Biofeedback intervention can significantly improve the attention and behavior of ADHD children and positively regulate the neural activity in related brain areas on the basis of drug treatment, suggesting that biofeedback therapy can be considered as a potential effective nondrug treatment option for ADHD children.

Integrin-Targeted Theranostic Nanoparticles for Clinical MRI-Traceable Treatment of Liver Fibrosis.

Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvß3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-ß (TGF-ß)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.

Single-Molecule Dendritic MRI Nanoprobes Reveal the Size-Dependent Tumor Entrance.

The tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade-off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) nanoprobes with well-defined sizes to precisely explore the size-dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)-chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r1 relaxivity and MR imaging signals increase with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold ≈8.0 nm achieves superior tumor accumulation and penetration. These single-molecule MRI nanoprobes can be served to precisely examine the size-related nanoparticle-biological interactions.

Surface chemistry mediates the tumor entrance of nanoparticles probed using single-molecule dual-imaging nanodots.

The active transport of nanoparticles into solid tumors through transcytosis has been recognized as a promising way to enhance tumor accumulation and penetration, but the effect of the physicochemical properties of nanoparticles remains unclear. Herein, we develop a type of single-molecule dual imaging nanodot by divergent growth of perylenediimide (PDI)-dye-cored polylysine dendrimers and internal orthogonal conjugation of Gd(III)-based macrocyclic probes for fluorescence imaging and magnetic resonance imaging (MRI) of surface chemistry-dependent tumor entrance. The MRI and fluorescence imaging show that sixth-generation nanodots with acetylated (G6-Ac) and oligo ethylene glycol (G6-OEG) surfaces exhibit similar high tumor accumulation but different intratumor distribution. Cellular uptake and transport experiments suggest that G6-Ac nanodots have lower lysosomal entrapment (61% vs. 83%) and a higher exocytotic rate (47% vs. 29%) than G6-OEG. Therefore, G6-Ac is more likely to undergo intercellular transport through cell transcytosis, and is able to reach a tumor area distant from blood vessels, while G6-OEG mainly enters the tumor through enhanced permeability and retention (EPR) effect-based passive transport, and is not able to deliver to distant tumor areas. This study suggests that it is possible to boost the tumor entrance of nanoparticles by engineering surface chemistry for active transport.

Supramolecular metal-organic frameworks as host-guest nanoplatforms for versatile and customizable biomedical applications.

Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we show a facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatform for customizable multifunctional imaging. These ß-CD-MOF nanoparticles were obtained with favorable morphology and size by controlling the degradation time. The ß-CD-MOF were used as nanoplatforms for facile functionalization with adamantane (Ad)-modified probes through host-guest interactions between the surface ß-CD units and Ad molecules. We demonstrated the method's feasibility and capability by developing various contrast agents for multiple biomedical imaging, including fluorescence imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging. The nanoprobes showed superior performance compared to the corresponding small molecular probes, including better physio-chemical properties (e.g., about 5 times of T1 relaxivity for MRI, 1.2 times of Hounsfield units for CT), improved pharmacokinetics, effective tissue imaging capability, and low safety concerns. These ß-CD-MOF-based nanoparticles are promising host-guest nanoplatforms for developing multifunctional and safe imaging probes. STATEMENT OF SIGNIFICANCE: Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we introduce facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatforms for customizable multifunctional imaging. The significance of this work includes: 1) This work reports the tailoring of MOFs nanoparticles with suitable sizes and shapes for biomedical applications through controllable morphological transition and degradation; 2) The ß-CD-MOF-based host-guest nanoplatforms are facile and feasible for developing multifunctional nanoparticular contrast agents for effective tissue imaging; 3) The nanoparticular contrast agents show low safety concerns with a long-term tissue deposition similar to the small molecular probes.

Effects of Talaromyces marneffei on Complete Blood Count by a Sysmex XN-9000 Analyzer.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection detected in the peripheral blood smears has been described by several reports. We studied the effects of T. marneffei in peripheral blood samples on complete blood count (CBC) using a Sysmex XN-9000 analyzer. METHODS: In a simulated T. marneffei infection model, blood samples with and without infectious diseases were selected, with high, medium, and low levels of white blood cell (WBC) and platelet (PLT) count, respectively. All samples were detected immediately and after a warm bath of 37℃ for 2 hours. RESULTS: WBC count of all samples was significantly increased by T. marneffei from a certain concentration and higher. For all samples, the effect of T. marneffei on WBC count after warm bath was significantly reduced compared to that on immediate WBC count from 4 - 6 x 109/L T. Marneffei and higher (p < 0.05). The presence of T. marneffei in all blood samples did not affect the results of PLT count. For all samples, the obvious effects of T. marneffei on WBC differential (WDF) and white cell nucleated red blood cell (WNR) scatter plots were from 4 - 6 x 109 T Marneffei and higher. CONCLUSIONS: As a kind of intracellular yeast, T. marneffei may affect WBC count, NRBC count, and WBC differential count of peripheral blood samples when the yeast concentration is (4 - 6) x 109 T Marneffei and higher. Moreover, the unique scatter plot cloud on WDF and WNR scatter plots caused by T. marneffei, may become an important clue pointing toward T. marneffei in peripheral blood.

Photodegradation of fleroxacin by g-C3N4/PPy/Ag and HPLC-MS/MS analysis of degradation pathways.

To improve the photocatalytic activity of g-C3N4, graphitic phase carbon nitride was prepared using melamine as the substrate and modified with PPy and Ag nanoparticles. The structure, morphology, and optical properties of the photocatalysts were investigated using various characterization methods such as XRD, FT-IR, TEM, XPS, and UV-vis DRS. The degradation of fleroxacin, a common quinolone antibiotic, was isolated and measured using the HPLC-MS/MS technique to trace its intermediates and deduce the main degradation pathways. The results showed that g-C3N4/PPy/Ag had high photocatalytic activity and a degradation rate of more than 90%. The fleroxacin degradation reactions were primarily oxidative ring opening of the N-methyl piperazine ring structure, defluorination reactions on fluoroethyl, HCHO, and N-methyl ethylamine removal reactions.

Switching ubiquitous and muscle-specific isoforms of mitochondrial respiratory complex IV in skeletal muscle fine-tunes complex IV activity.

Respiratory complex IV (CIV, cytochrome c oxidase) is the terminal enzyme of the mitochondrial electron transport chain. Some CIV subunits have two or more isoforms, which are ubiquitously expressed or are expressed in specific tissues like the lung, muscle, and testis. Among the tissue-specific CIV isoforms, the muscle-specific isoforms are expressed in adult cardiac and skeletal muscles. To date, the physiological and biochemical association between the muscle-specific CIV isoforms and aerobic respiration in muscles remains unclear. In this study, we profiled the CIV organization and expression pattern of muscle-specific CIV isoforms in different mouse muscle tissues. We found extensive CIV-containing supramolecular organization in murine musculature at advanced developmental stages, while a switch in the expression from ubiquitous to muscle-specific isoforms of CIV was also detected. Such a switch was confirmed during the in vitro differentiation of mouse C2C12 myoblasts. Unexpectedly, a CIV expression decrease was observed during C2C12 differentiation, which was probably due to a small increase in the expression of muscle-specific isoforms coupled with a dramatic decrease in the ubiquitous isoforms. We also found that the enzymatic activity of CIV containing the muscle-specific isoform COX6A2 was higher than that with COX6A1 in engineered HEK293T cells. Overall, our results indicate that switching the expression from ubiquitous to muscle-specific CIV isoforms is indispensable for optimized oxidative phosphorylation in mature skeletal muscles. We also note that the in vitro C2C12 differentiation model is not suitable for the study of muscular aerobic respiration due to insufficient expression of muscle-specific CIV isoforms.

Metagenomic insight of fluorene-boosted sludge acidogenic fermentation: Metabolic transformation of amino acids and monosaccharides.

Fluorene (Flu) occurs widely in various environments and its toxicity to organisms is well-known. However, the impact of Flu on complicated biochemical processes involving functional microbial community has been reported rarely. In this study, the facilitation of Flu on the volatile fatty acids (VFAs) generation executed by acidogenic microbial population during sludge acidogenic fermentation (37 °C, SRT = 8 d, pH = 10.0) was investigated. The accumulation of VFAs (particularly acetic acid) increased initially and then declined with the increasing of Flu concentration (0-500 mg/kg dry sludge), which reached a maximum (3211.1 mg COD/L) as Flu content was 200 mg/kg dry sludge. The Flu-enhanced VFAs production was primarily attributed to the shift of hydrolysis/acidification, as well as the corresponding functional microbial community and the activity of enzymes. Based on the metagenomics analysis, the conversion of organic substrates, i.e. amino acid and monosaccharide, into VFAs embraced in hydrolysis/acidification shaped by Flu was constructed at the genetic level. The relative abundances of genes included in aminotransfer and deamination process of amino acid and glycolysis of monosaccharide into VFA-precursors (pyruvate, acetyl-CoA and propionyl-CoA), and the further formation of VFAs were improved due to the Flu presence. This study shed light on the Flu-affected microbial processes at the molecular biology level during acidogenic fermentation and was of great significance in resource recovery of sludge containing persistent organic pollutants.

Real-Time Objective Evaluation of the Ischemic Stroke through pH-Responsive Fluorescence Imaging.

A rapid and comprehensive assessment of ischemic stroke (IS) is critical for clinicians to take the most appropriate treatment. Currently, IS assessment is mainly carried out by computed tomography and magnetic resonance imaging in combination with observing the clinical symptoms and inquiring about contraindications. However, they cannot diagnose pathological conditions and judge the microenvironment in real-time. Near-infrared fluorescence imaging has advantages for IS imaging, such as high sensitivity, high spatiotemporal resolution, and straightforward real-time operation. Herein, a pH-responsive fluorescent liposomal probe (BOD@Lip) is prepared for in vivo real-time visualization of the degree of IS based on the different acid microenvironments in the progression of the disease. The fluorescence imaging with BOD@Lip shows the degree of IS, and the correlation between fluorescence signals and the neurological deficit scores is established for the first time. This work provides a new method to objectively evaluate the degree of IS through a visualized route and a new insight into the relationship between the acidic microenvironment and the progression of IS.

Novel manganese and polyester dendrimer-based theranostic nanoparticles for MRI and breast cancer therapy.

Therapeutic nanoplatforms are widely used in the diagnosis and treatment of breast cancer due to the merits of enabling high soft-tissue resolution and the availability of numerous therapeutic nanoparticles. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. We found that MHD could greatly enhance MRI contrast with a longitudinal relaxivity of 5.8 mM-1 s-1 due to the Mn-based paramagnetic dendrimer carrier. Meanwhile, the MRI-guided PDT inhibition of breast tumors could be achieved by the hypericin-carrying MHD and further improved by Mn2+-mediated alleviation of the hypoxic microenvironment and the enhancement of cellular ROS. Besides, MHD showed excellent biocompatibility and biosafety with liver and kidney clearance mechanisms. Thus, the high efficiency in MRI contrast enhancement and excellent tumor-inhibiting effects indicate MHD's potential as a novel, stable, and multifunctional nanotheranostic agent for breast cancer.

Thrombotic Thrombocytopenic Purpura After Radiofrequency Ablation of Hepatocellular Carcinoma: A Case Report.

Radiofrequency ablation (RFA) has become one of the commonly used treatment methods for hepatocellular carcinoma (HCC). It is widely available in the clinic and presents the advantages of short recovery time and a less invasive approach. Only a few complications, such as hemorrhage, ascites, and duct injury, have been reported after RFA for HCC. Herein, we report for the first time the case of a patient diagnosed with recurrent HCC in whom thrombotic thrombocytopenic purpura (TTP) was diagnosed as a complication of the RFA procedure. A 64-year-old male patient with a 2-year history of resected-stage V HCC, in whom later recurrence occurred, underwent RFA for HCC. This patient had a rapid drop in platelets and some petechiae on the wrists after RFA. Combining the clinical and laboratory tests, the diagnosis of TTP was reached. We immediately used plasmapheresis combined with drug therapy, which successfully treated the clinical condition of TTP, with no evidence of recurrence or other complications 1 year after initial treatment. TTP is a rare complication of RFA procedures. Prompt diagnosis and aggressive treatment measures are critical. Through this case report, we hope to raise awareness of the complications of RFA.

Evaluating the economic impacts of COVID-19 pandemic on shipping and port industry: A case study of the port of Shanghai.

The stability of shipping and port operations are crucial for international trade and global supply chain. However, the COVID-19 pandemic hit the shipping and port industry enormously in late 2019, and continues till now. It is important to identify the impacts of the pandemic on shipping and port operations and evaluate the potential economic impacts for better setting future development strategies and policies. A System Dynamics (SD) model is proposed to depict the impact transmission within the supply chain considering 5 sub-systems (shipping, port, transportation, manufacturing and social). Potential economic impacts which are represented by the shipping loss and port loss will be assessed. 6 scenarios with different epidemic durations and capacity recovery degrees have been set to investigate the economic impacts. The port of Shanghai, together with the container shipping business is selected as input for case study. Results indicate that in the first few months the port and carriers may suffer economic loss due to shrunken demand caused by COVID-19. But later carriers may enjoy an increase of income compared to non-pandemic scenario owing to strong recovery in most scenarios. Moreover, we found that manufacturing, transportation and port operation capacities would jointly affect the recovery process and economic impacts. The findings can facilitate policy makers in making port management and future industry development decisions.

Can the combination of DWI and T2WI radiomics improve the diagnostic efficiency of cervical squamous cell carcinoma?

BACKGROUND: To investigate the value of MRI multi-sequence imaging model in differentiation of cervical squamous cell carcinoma (CSCC). METHODS: A total of 104 CSCC patients confirmed with pathology were retrospectively enrolled. All patients underwent conventional MRI examination before treatment. The lesions were segmented using ITK-SNAP software manually and radiomics features were extracted by Artificial Intelligence Kit (AK) software. 396 tumor texture features were obtained and then the mRMR and Lasso algorithms were used to reduce the feature dimension. Three models including T2WI model, DWI model and Joint model (combined TWI and DWI) were constructed in training group and evaluated in validation group. and the receiver operator characteristics and calibration curve were used to evaluate the model performance. RESULTS: The Joint model and T2WI model both showed a better diagnostic efficacy than single DWI model in differentiation of CSCC in training group (Joint model: AUC = 0.841; T2WI model: AUC = 0.804; DWI model: AUC = 0.732) and validation group (Joint model: AUC = 0.822; T2WI model: AUC = 0.791; DWI model: AUC = 0.724). But there was no statistical difference between Joint model and T2WI model by Delong test(P > 0.05). CONCLUSIONS: The study suggested that the conventional T2WI sequence may be more suitable for prognosis evaluation of CSCC, which can provide a potential tool to facilitate the differential diagnosis of low-differentiation and high-differentiation CSCC.

Immature Erythroid Precursors and/or Erythrocyte Dysplasia in Peripheral Blood.

BACKGROUND: With the progress of technology in automated hematology analyzers, in the vast majority of cases, nucleated red corpuscles (NRC) can be automatically identified by most types of automated hematology analyzers, thus correcting the leukocyte count and avoiding pseudoleukocytosis by the analyzers themselves. The objective of the study was to explore pseudoleukocytosis due to immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood resulting from different rare situations. METHODS: Four rare cases showing pseudoleukocytosis due to immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood were analyzed and the effects on complete blood count (CBC) performed on a Sysmex XN-2000 analyzer and microscopic morphological features of the peripheral blood were investigated. These cases were selected for their vital value in describing all pseudoleukocytosis due to immature erythroid pre-cursors and/or erythrocyte dysplasia in the peripheral blood. The causes of immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood were analyzed. RESULTS: In all these cases, proportions of NRC and leukocyte counts were affected to varying degrees by the presence of numerous immature erythroid precursors and/or obvious erythrocyte dysplasia in the peripheral blood. All cases associated with an alarm concerning NRC presentation, and abnormal scattergrams of WDF and WNR, thus leading to pseudoleukocytosis. CONCLUSIONS: Laboratory artifacts led by NRC may be an indicator towards the occurrence of numerous immature erythroid precursors and/or obvious erythrocyte dysplasia in the peripheral blood, and active extramedullary hematopoiesis, breakdown of the bone marrow barrier, and the stress response of acute bleeding and severe multiple infection.

Neutrophil-to-lymphocyte ratio and lactate dehydrogenase for early diagnosis of AIDS patients with Talaromyces marneffei infection.

BACKGROUND: This study aimed to explore the value of neutrophil-to-lymphocyte ratio (NLR) in combination with routine blood tests, lactate dehydrogenase (LDH), and T-lymphocyte subsets for the early diagnosis of acquired immunodeficiency syndrome (AIDS) combined with Talaromyces marneffei (TM) infection. METHODS: A total of 166 confirmed AIDS patients were enrolled in this study. The observation group included 80 AIDS patients with TM infection, and the control group consisted of 86 AIDS patients with other complications. Regression analysis was performed to evaluate the predictive value of each index and the combination of these indexes for AIDS combined with TM infection using receiver operating characteristic (ROC) curve analysis. RESULTS: NLR and LDH were significantly higher in patients in the observation group compared with those in the control group, and the differences were statistically significant (P<0.05). There was no statistical difference in platelets, infantile granulocytes (IGM), and nucleated red blood cells (NRBC) between the 2 groups (P>0.05). The area under the operating characteristic curve (AUC) of the observed indicators were: NLR, 0.628; hemoglobin (HGB), 0.704; LDH, 0.607; lymphocyte (LYM) count, 0.744; CD4+ T lymphocyte count, 0.789; and CD8+ T lymphocyte count, 0.701. The combined AUC of multiple indicators was 0.815, with a sensitivity and specificity of 76.2% and 76.1%, respectively. CONCLUSIONS: NLR, HGB, LYM, LDH, and T lymphocyte subsets were diagnostic for early AIDS combined with TM infection , and CD4+ T lymphocytes had the best diagnostic efficacy alone.

Estimating the economic loss of a seaport due to the impact of COVID-19.

Sea ports are key nodes of global trade and economy, but are vulnerable to hazards, catastrophes and epidemic outbreaks. Since the emergence of COVID-19 infection at the end of 2019, the operations of seaports, especially container ports have been hit hard. This paper aims to explore the impacts of COVID-19 on container ports' operations, clarify the potential economic losses of ports and propose coping suggestions for recovery. Five scenarios of port recovery have been set and the revenues of the port under epidemic outbreaks are estimated. The economic loss could be modeled as the difference between original revenue a port should obtained without the impact of COVID-19 and the actual revenue considering the impact of COVID-19. The container port of Shanghai is selected as the case study. Results and sensitivity analysis reveal that slower the recovery develops, much more loss will be borne by the port. However, there is also a possibility that the port achieves increased income with a surging boom of shipping demand. The loss of port due, handling service, facility security fee and berthage charge are major losses. Besides, port handling efficiency and fleet structure are also found crucial for reducing economic losses. Reducing containership's handling time and serving larger ships would also help the port reduce economic losses.