Cancer-Associated Fibroblasts Promote Lymphatic Metastasis in Cholangiocarcinoma via the PDGF-BB/PDGFR-ß Mediated Paracrine Signaling Network.

Patients with cholangiocarcinoma (CCA) with lymph node metastasis (LNM) have the worst prognosis, even after complete resection; however, the underlying mechanism remains unclear. Here, we established CAF-derived PDGF-BB as a regulator of LMN in CCA. Proteomics analysis revealed upregulation of PDGF-BB in CAFs derived from patients with CCA with LMN (LN+CAFs). Clinically, the expression of CAF-PDGF-BB correlated with poor prognosis and increased LMN in patients with CCA, while CAF-secreted PDGF-BB enhanced lymphatic endothelial cell (LEC)-mediated lymphangiogenesis and promoted the trans-LEC migration ability of tumor cells. Co-injection of LN+CAFs and cancer cells increased tumor growth and LMN in vivo. Mechanistically, CAF-derived PDGF-BB activated its receptor PDGFR-ß and its downstream ERK1/2-JNK signaling pathways in LECs to promote lymphoangiogenesis, while it also upregulated the PDGFR-ß-GSK-P65-mediated tumor cell migration. Finally, targeting PDGF-BB/PDGFR-ß or the GSK-P65 signaling axis prohibited CAF-mediated popliteal lymphatic metastasis (PLM) in vivo. Overall, our findings revealed that CAFs promote tumor growth and LMN via a paracrine network, identifying a promising therapeutic target for patients with advanced CCA.

Iterative Reconstruction Algorithms in Magneto-Acousto-Electrical Computed Tomography (MAE-CT) for Image Quality Improvement.

Magneto-acousto-electrical computed tomography (MAE-CT) is a recently developed rotational magneto-acousto-electrical tomography (MAET) method, which can map the conductivity parameter of tissues with high spatial resolution. Since the imaging mode of MAE-CT is similar to that of CT, the reconstruction algorithms for CT are possible to be adopted for MAE-CT. Previous studies have demonstrated that the filtered back-projection (FBP) algorithm, which is one of the most common CT reconstruction algorithms, can be used for MAE-CT reconstruction. However, FBP has some inherent shortcomings of being sensitive to noise and non-uniform distribution of views. In this study, we introduced iterative reconstruction (IR) method in MAE-CT reconstruction and compared its performance with that of the FBP. The numerical simulation, the phantom, and in vitro experiments were performed, and several IR algorithms (ART, SART, SIRT) were used for reconstruction. The results show that the images reconstructed by the FBP and IR are similar when the data is noise-free in the simulation. As the noise level increases, the images reconstructed by SART and SIRT are more robust to the noise than FBP. In the phantom experiment, noise and some stripe artifacts caused by the FBP are removed by SART and SIRT algorithms. In conclusion, the IR method used in CT is applicable in MAE-CT, and it performs better than FBP, which indicates that the state-of-the-art achievements in the CT algorithm can also be adopted for the MAE-CT reconstruction in the future.

Visualization of photothermal therapy by semiconducting polymer dots mediated photoacoustic detection in NIR II.

Visualization of photothermal therapy mediated by photothermal transduction agents (PTAs) is important to promote individual treatment of patients with low side effects. Photoacoustic detection has emerged as a promising noninvasive method for the visualization of PTAs distribution but still has limitations in temperature measurement, including poor measurement accuracy and low tissue penetration depth. In this study, we developed biocompatible semiconducting polymer dots (SPD) for in situ coupling of photothermal and photoacoustic detection in the near-infrared II window. SPD has dual photostability under pulsed laser and continuous-wave laser irradiation with a photothermal conversion efficiency of 42.77%. Meanwhile, a strong correlation between the photoacoustic signal and the actual temperature of SPD can be observed. The standard deviation of SPD-mediated photoacoustic thermometry can reach 0.13 °C when the penetration depth of gelatin phantom is 9.49 mm. Preliminary experimental results in vivo show that SPD-mediated photoacoustic signal has a high signal-to-noise ratio, as well as good performance in temperature response and tumor enrichment. Such a study not only offers a new nanomaterial for the visualization of photothermal therapy but will also promote the theranostic platform for clinical applications.

Automatic Diagnosis of Significant Liver Fibrosis From Ultrasound B-Mode Images Using a Handcrafted-Feature-Assisted Deep Convolutional Neural Network.

The accurate diagnosis of significant liver fibrosis ( ≥ F2) in patients with chronic liver disease (CLD) is critical, as ≥ F2 is a crucial factor that should be considered in selecting an antiviral therapy for these patients. This article proposes a handcrafted-feature-assisted deep convolutional neural network (HFA-DCNN) that helps radiologists automatically and accurately diagnose significant liver fibrosis from ultrasound (US) brightness (B)-mode images. The HFA-DCNN model has three main branches: one for automatic region of interest (ROI) segmentation in the US images, another for attention deep feature learning from the segmented ROI, and the third for handcrafted feature extraction. The attention deep learning features and handcrafted features are fused in the back end of the model to enable more accurate diagnosis of significant liver fibrosis. The usefulness and effectiveness of the proposed model were validated on a dataset built upon 321 CLD patients with liver fibrosis stages confirmed by pathological evaluations. In a fivefold cross validation (FFCV), the proposed model achieves accuracy, sensitivity, specificity, and area under the receiver-operating-characteristic (ROC) curve (AUC) values of 0.863 (95% confidence interval (CI) 0.820-0.899), 0.879 (95% CI 0.823-0.920), 0.872 (95% CI 0.800-0.925), and 0.925 (95% CI 0.891-0.952), which are significantly better than those obtained by the comparative methods. Given its excellent performance, the proposed HFA-DCNN model can serve as a promising tool for the noninvasive and accurate diagnosis of significant liver fibrosis in CLD patients.

Cancer-specific survival in patients with cholangiocarcinoma after radical surgery: a Novel, dynamic nomogram based on clinicopathological features and serum markers.

BACKGROUND: This study aims to (1) identify preoperative testing-based characteristics associated with enhanced prognosis and survival for cholangiocarcinoma patients, and (2)create a distinctive nomogram to anticipate each patient's cancer-specific survival (CSS). METHODS: Retrospective analysis was performed on 197 CCA patients who underwent radical surgery at Sun Yat-sen Memorial Hospital; they were divided into a 131-person "training cohort" and a 66-person "internal validation cohort." The prognostic nomogram was created following a preliminary Cox proportional hazard regression search for independent factors influencing the patients' CSS. Its applicable domain was examined via an external validation cohort, which included 235 patients from the Sun Yat-sen University Cancer Center. RESULTS: The median follow-up period for the 131 patients in the training group was 49.3 months (range, 9.3 to 133.9 months). One-, three-, and five-year CSS rates were 68.7%, 24.5%, and 9.2%, respectively, with the median CSS length being 27.4 months (range: 1.4 to 125.2 months). PLT, CEA, AFP, tumor location, differentiation, lymph node metastasis, chemotherapy, and TNM stage were determined to be independent risk factors for CCA patients by univariate and multivariate Cox proportional hazard regression analysis. We were able to accurately predict postoperative CSS after incorporating all of these characteristics into a nomogram. The AJCC's 8th edition staging method's C-indices were statistically substantially (P < 0.001) lower than the nomogram's C-indices (0.84, 0.77, and 0.74 in the training, internal and external validation cohorts respectively). CONCLUSIONS: A realistic and useful model for clinical decision-making and the optimization of therapy is presented as a nomogram that includes serum markers and clinicopathologic features for predicting postoperative survival in cholangiocarcinoma.

Dynamic Speed of Sound Adaptive Transmission-Reflection Ultrasound Computed Tomography.

Ultrasound computed tomography (USCT) can visualize a target with multiple imaging contrasts, which were demonstrated individually previously. Here, to improve the imaging quality, the dynamic speed of sound (SoS) map derived from the transmission USCT will be adapted for the correction of the acoustic speed variation in the reflection USCT. The variable SoS map was firstly restored via the optimized simultaneous algebraic reconstruction technique with the time of flights selected from the transmitted ultrasonic signals. Then, the multi-stencils fast marching method was used to calculate the delay time from each element to the grids in the imaging field of view. Finally, the delay time in conventional constant-speed-assumed delay and sum (DAS) beamforming would be replaced by the practical computed delay time to achieve higher delay accuracy in the reflection USCT. The results from the numerical, phantom, and in vivo experiments show that our approach enables multi-modality imaging, accurate target localization, and precise boundary detection with the full-view fast imaging performance. The proposed method and its implementation are of great value for accurate, fast, and multi-modality USCT imaging, particularly suitable for highly acoustic heterogeneous medium.

Magnetomotive Ultrasound Shear Wave Elastography (MMUS-SWE): A Validation Study From Simulations to Experiments.

Ultrasound elastography is a functional imaging method that enables the measurement of soft tissue elasticity, which is associated with the pathological process of many diseases. However, the measurement area of the conventional elastography method is subjectively selected. Inspired by the targeted imaging technology, we propose a method of magnetomotive ultrasound shear wave elastography (MMUS-SWE). This method utilizes the magnetic force between the magnetic nanoparticles (MNPs) and the external magnetic field to generate shear waves. Then, it can detect the distribution of MNPs and the elasticity of the tissue around the MNPs. As MNPs have been widely used for targeted labeling, the strategy to induce local vibration by MNPs will be more specific than that of the conventional SWE. In this study, the theoretical feasibility was verified by the finite element simulation model. Then, an experimental system was built, and the experimental feasibility of the method was demonstrated through phantom experiments, in vitro tissue experiments, and in vivo experiments. The results show that the distribution of the MNPs and the elastic information of tissues surrounding the MNPs can be detected simultaneously. This technology is expected to realize targeted elasticity measurement based on the MNPs and has potential applications for disease diagnosis.

Real-world experience of postoperative adjuvant chemoimmunotherapy in patients with perihilar cholangiocarcinoma at high risk of recurrence.

BACKGROUND: This study aimed to assess whether postoperative adjuvant chemoimmunotherapy could lead to better clinical outcomes for high-risk patients with perihilar cholangiocarcinoma (pCCA). METHODS: In the cohort study, we retrospectively reviewed patients who received surgical resection for pCCA with curative intent from January 2018 to December 2021 at the Sun Yat-sen Memorial Hospital. The patients at high risk for relapse were further analyzed. Among them, 20 patients received adjuvant chemoimmunotherapy, 28 patients received adjuvant chemotherapy, and 33 patients received surgery alone. The oncological outcomes and drug-associated adverse events were evaluated. RESULTS: The 2-year overall survival (OS) rates in patients treated with adjuvant chemoimmunotherapy, adjuvant chemotherapy, and surgery alone were 80.0%, 49.4% and 22.6%, respectively. Univariable and multivariable Cox analyses showed that the treatment regimen and TNM stage were associated with adverse OS. Adjuvant chemoimmunotherapy led to an increase in OS compared with adjuvant chemotherapy [hazard ratio (HR) = 3.253; 95% confidence interval (CI) 1.072-9.870; P = 0.037] or surgery alone (HR = 7.560; 95% CI 2.508-22.785; P < 0.001). The median recurrence-free survival was 22.0 months for the adjuvant chemoimmunotherapy group, 17.0 months for the adjuvant chemotherapy group, and 13.2 months for the surgery alone group (P = 0.177); these differences were not significant. The chemoimmunotherapy group was associated with more frequent hematological side effects than the chemotherapy group, but the difference was not statistically significant. CONCLUSION: Postoperative adjuvant chemoimmunotherapy for resected pCCA patients showed improved OS compared with adjuvant chemotherapy or surgery alone, and further prospectively randomized controlled trials are necessary to validate these results.

CCL3 secreted by hepatocytes promotes the metastasis of intrahepatic cholangiocarcinoma by VIRMA-mediated N6-methyladenosine (m6A) modification.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignant disease characterized by onset occult, rapid progression, high relapse rate, and high mortality. However, data on how the tumor microenvironment (TME) regulates ICC metastasis at the transcriptomic level remains unclear. This study aimed to explore the mechanisms and interactions between hepatocytes and ICC cells. METHODS: We analyzed the interplay between ICC and liver microenvironment through cytokine antibody array analysis. Then we investigated the role of N6-methyladenosine (m6A) modification and the downstream target in vitro, in vivo experiments, and in clinical specimens. RESULTS: Our study demonstrated that cytokine CCL3, which is secreted by hepatocytes, promotes tumor metastasis by regulating m6A modification via vir-like m6A methyltransferase associated (VIRMA) in ICC cells. Moreover, immunohistochemical analyses showed that VIRMA correlated with poor outcomes in ICC patients. Finally, we confirmed both in vitro and in vivo that CCL3 could activate VIRMA and its critical downstream target SIRT1, which fuels tumor metastasis in ICC. CONCLUSIONS: In conclusion, our results enhanced our understanding of the interaction between hepatocytes and ICC cells, and revealed the molecular mechanism of the CCL3/VIRMA/SIRT1 pathway via m6A-mediated regulation in ICC metastasis. These studies highlight potential targets for the diagnosis, treatment, and prognosis of ICC.

The clinical effect of primary duct closure and T-tube drainage: A propensity score matched study.

BACKGROUND: Although laparoscopic common bile duct exploration (LCBDE) is considered a safe and effective method for the removal of bile duct stones, selecting primary duct closure (PDC) or T-tube drainage (TTD) following choledochotomy remains controversial. This study aims to explore the clinical effects of PDC and TTD after LCBDE. METHODS: We retrospectively analyzed clinical data of 348 patients with choledocholithiasis treated with LCBDE from January 2016 to October 2020. All patients were divided into PDC (225 cases) and TTD (123 cases) groups. Propensity score matching (PSM) was performed. We compared operative parameters and outcomes. RESULTS: After matching (n = 116/group), no significant difference was observed between the two groups (P > 0.05) regarding intra-abdominal infection, incision infection, bile leakage, and retained stones. In terms of operation time, intraoperative blood loss, postoperative hospital stay, postoperative exhaust time, postoperative antibiotic use time, and postoperative abdominal drainage time, PDC group was obviously superior to TTD group (P < 0.05). CONCLUSION: Primary closure following LCBDE is considered a safe and effective alternative to T-tube drainage.

Improved Magneto-Acousto-Electrical Computed Tomography (MAE-CT) With Multi-Angle Plane Wave Excitation.

As a tissue conductivity imaging method, magneto-acousto-electric tomography (MAET) has the advantage of high axial spatial resolution compared with traditional electrical impedance imaging methods. However, it has the problems of difficulty in imaging targets with irregular conductivity distribution and poor lateral spatial resolution. Although the rotation-based MAET method can partly solve the irregular target problem, there is still a poor imaging signal-to-noise ratio (SNR) problem. Our previous study established a framework of an innovative MAET method, which has a very similar imaging theory and reconstruction algorithm to those of computed tomography (CT). Therefore, we name the method magneto-acoustic-electric computed tomography (MAE-CT). This paper proposes an improved implementation of MAE-CT based on multi-angle plane wave excitation. This method combines the electronic steering of the linear array transducer with the mechanical rotation to increase the number of projection angles while keeping the imaging complexity. In this study, we first established a finite element simulation model to verify the method's feasibility. Then phantom experiments were conducted to systematically investigate the performance of the proposed method. Finally, in vitro liver tissue experiment was conducted to further explore the feasibility of the method. The experimental results show that our method improves both the SNR and spatial resolution of the reconstructed image. For the phantom results, this method can detect conductivity of 0.67 S/m in an area with a size of 2 mm. To the best of our knowledge, this is the best result of spatial resolution available for MAET.

Biodegradable Carbon Dioxide-Derived Non-Viral Gene Vectors for Osteosarcoma Gene Therapy.

Osteosarcoma often occurs in children and adolescents with high invasiveness and high mortality. Polo-like kinase 1 (PLK1) overexpressed in most tumors promotes cancer cell proliferation and transformation. PLK1 is considered as a therapeutic target for osteosarcoma. RNA interference-based therapies are employed to combat osteosarcoma through silencing PLK1 gene expression. However, the treatment results remain unsatisfactory due to the lack of a safe and efficient nonviral gene vector. To tackle this hurdle, biodegradable and CO2 -derivative cationic poly(vinylcyclohexene carbonates) (CPCHCs) are used as gene vectors to perform a siPLK1 therapeutic strategy for osteosarcoma treatment. Of those CPCHCs, CPCHC60 demonstrates the most excellent performance in gene transfection efficiency, endo-lysosome escaping, biodegradability, and biosafety. With the treatment of CPCHCs/siRNA nanoparticles, the expression level of PLK1 gene in osteosarcoma cells is significantly down-regulated. Subsequently, cells are arrested in the G2 /M phase and subsequently dead in the form of apoptosis, resulting in significant tumor regression both in vitro and in vivo. This study brings a new insight into the development of superior nonviral gene vectors for practical cancer treatment. Based on the results, the resulting nanoparticle-based gene drug formation is considered to have a highly successful chance in further translational nanomedicine applications.

Hepatitis B Virus Surface Antigen Promotes Stemness of Hepatocellular Carcinoma through Regulating MicroRNA-203a.

Background and Aims: Patients with persistent positive hepatitis B surface antigen (HBsAg), even with a low HBV-DNA load, have a higher risk of hepatocellular carcinoma (HCC) than those without HBV infection. Given that tumor stemness has a critical role in the occurrence and maintenance of neoplasms, this study aimed to explore whether HBsAg affects biological function and stemness of HCC by regulating microRNA, and to explore underlying mechanisms. Methods: We screened out miR-203a, the most significant down-regulated microRNA in the microarray analysis of HBsAg-positive samples and focused on that miRNA in the ensuing study. In vitro and in vivo functional experiments were performed to assess its regulatory function. The effect of miR-203a on stemness and the possible correlation with BMI1 were analyzed in this study. Results: MiR-203a was significantly down-regulated in HBsAg-positive HCC with the sharpest decrease shown in microarray analysis. The negative correlation between miR-203a and HBsAg expression was confirmed by quantitative real-time PCR after stimulation or overexpression/knockdown of HBsAg in cells. We demonstrated the function of miR-203a in inhibiting HCC cell proliferation, migration, clonogenic capacity, and tumor development in vivo. Furthermore, the overexpression of miR-203a remarkably increases the sensitivity of tumor cells to 5-FU treatment and decreases the proportion of HCC cells with stem markers. In concordance with our study, the survival analysis of both The Cancer Genome Atlas database and samples in our center indicated a worse prognosis in patients with low level of miR-203a. We also found that BMI1, a gene maintains the self-renewal capacity of stem cells, showed a significant negative correlation with miR-203a in HCC specimen (p<0.001). Similarly, opposite BMI1 changes after overexpression/knockdown of miR-203a were also confirmed in vitro. Dual luciferase reporting assay suggested that miR-203a may regulate BMI1 expression by direct binding. Conclusions: HBsAg may promote the development of HCC and tumor stemness by inhibiting miR-203a, resulting in poor prognosis. miR-203a may serve as a crucial treatment target in HBsAg-positive HCC. More explicit mechanistic studies and animal experiments need to be conducted as a next step.

Exosomal miR-4800-3p Aggravates the Progression of Hepatocellular Carcinoma via Regulating the Hippo Signaling Pathway by Targeting STK25.

Background: Emerging evidence has shown that exosome microRNAs (miRNAs) regulate the development of hepatocellular carcinoma (HCC). Here, the influences of miR-4800-3p on the progression of HCC were explored. Materials and Methods: The expression of miR-4800-3p in the exosome derived by transforming growth factor beta 1 (TGF-ß1)-treated HCC cells and the serum exosome isolated from HCC patients were identified by real-time PCR. The effects of TGF-ß1 and the influences of Huh7-secreted exosomes and the effects of miR-4800-3p combined with/without STK25 on cell functions were explored using the EdU assay cloning experiments, wound healing assay, and Transwell assay. The corresponding molecular mechanisms were further detected using Western blot and real-time PCR assays. The combination of miR-4800-3p and STK25 was verified by the dual-luciferase and RNA pulldown assays. The influences of miR-4800-3p on the growth and epithelial-mesenchymal transformation (EMT) of implanted tumors were tested in vivo and further confirmed by Western blot. Results: The miR-4800-3p expression was highly expressed in both exosomes derived by TGF-ß1-treated HCC cells and the serum exosomes of HCC patients. In the cases of treatment with both Huh7-derived exosomes, the level of miR-4800-3p expression was highest, and the treatment of TGF-ß1 could greatly promote the proliferation, stemness, migration, and invasion of HCC cells via upregulating the markers of stemness and EMT, including CD44, CD133, OCT4, N-cadherin, E-cadherin, and ZO-1. Similar results could be obtained when miR-4800-3p was overexpressed in HCC cells. Furthermore, downregulation of STK25 expression, a direct target gene of miR-4800-3p, could greatly rescue the malignant biological behaviors aggravated by overexpression of miR-4800-3p. This was achieved by suppressing the expression of CD44, CD133, OCT4, N-cadherin, and PCNA and activating the Hippo pathway while increasing E-cadherin and ZO-1. Similar results were also obtained in vivo that knockdown of miR-4800-3p expression suppressed tumor growth induced by Huh7-derived exosomes by mediating the EMT markers and the Hippo signaling pathway. Conclusion: Exosomal miR-4800-3p could accelerate HCC development by regulating the Hippo signal by targeting STK25, which could be used as a new therapeutic target for HCC treatment.

Complete Response to Combined Chemotherapy and Anti-PD-1 Therapy for Recurrent Gallbladder Carcinosarcoma: A Case Report and Literature Review.

Background: Gallbladder carcinosarcoma (GBCS) is a rare and aggressive malignancy with extremely poor prognosis. Although surgery is regarded as the primary therapy for GBCS, the effective therapeutic strategies for unresected lesions have been poorly defined. Case Presentation: We presented a case of a 74-year-old male who underwent radical resection of gallbladder carcinoma at a local hospital. Seven months later, he was admitted to our hospital due to right upper abdominal discomfort. Postoperative radiological examinations showed multiple hepatic lesions, hilar lymph node metastasis, and main portal vein tumor thrombus. The pathological consultation results confirmed GBCS and immunohistochemical examinations revealed PD-L1 expression in 20% of tumor cells. Then, the patient received chemotherapy (Gemcitabine plus Oxaliplatin, GEMOX) in combination with anti-PD-1 therapy. After nine courses of the combination therapy, complete regression of the tumors was achieved with no evidence of relapse till now. Conclusions: We, for the first time, reported a patient with recurrent GBCS who benefited from the combined chemotherapy and immunotherapy, providing a potential effective management strategy for the refractory malignant tumor.

Immune Checkpoint FGL1 Expression of Circulating Tumor Cells Is Associated With Poor Survival in Curatively Resected Hepatocellular Carcinoma.

LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P<0.001) and distant metastasis(P=0.020) in FGL1 positive patients was higher than that of FGL1 negative patients. In addition, patients with FGL1 positive circulating tumor cells had worse postoperative survival than FGL1 negative patients (p=0.0297). The mixed phenotypic CTC presented a higher level of FGL1 expression than any other types, the number of which also predicted worse prognosis(p=0.0443). We also found that the expression of FGL1 on CTCs was associated with the level of FGL1 in tumor tissues. Of 12 patients receiving PD-1/PD-L1 blockade in a total of 109 cases, 8 out of 10 patients with FGL1 positive CTC showed immunotherapy resistance. It is the first study that suggested FGL1 expression in CTCs as an indicator of the poor prognosis in HCC patients. CTC detection may serve as a promising replacement for determination of tumor tissue FGL1 expression and provide evidence for the application of immunotherapy.

A Dual-Modal Imaging Method Combining Ultrasound and Electromagnetism for Simultaneous Measurement of Tissue Elasticity and Electrical Conductivity.

The mechanical and electrical properties of soft tissues are relative to soft tissues' pathological state. Modern medical imaging devices have shown a trend to multi-modal imaging, which will provide complementary functional information to improve the accuracy of disease diagnosis. However, no method or system can simultaneously measure the mechanical and electrical properties of the soft tissue. In this study, we proposed a novel dual-modal imaging method integrated by shear wave elasticity imaging (SWEI) and Magneto-acousto-electrical tomography (MAET) to measure soft tissue's elasticity and conductivity simultaneously. A dual-modal imaging system based on a linear array transducer is built, and the imaging performances of MAET and SWEI were respectively evaluated by phantoms experiment and in vitro experiment. Conductivity phantom experiments show that the MAET in this dual-modal system can image conductivity gradient as low as 0.4 S/m. The phantom experiments show that the reconstructed 2-D elasticity maps of the phantoms with inclusions with a diameter larger than 5 mm are relatively accurate. In vitro experiments show that the elasticity parameter can significantly distinguish the changes in tissue before and after heating. This study first proposes a method that can simultaneously obtain tissue elasticity and electrical conductivity to the best of our knowledge. Although this paper just carried out the proof of concept experiments of the new method, it demonstrates great potential for disease diagnosis in the future.

Synthetic Conjugated Oligoelectrolytes Are Effective siRNA Transfection Carriers: Relevance to Pancreatic Cancer Gene Therapy.

Conjugated oligoelectrolyte COE-S6 contains an elongated conjugated core with three cationic charges at each termini of the internal core. As an analogue of bolaamphiphiles, these structural attributes lead to the formation of spherical nanoplexes with Dh = 205 ± 5.0 nm upon mixing with small interfering RNA (siRNA). COE-S6/siRNA nanocomplexes were shown to be protective toward RNase, stimulate endosome escape, and achieve transfection efficiencies comparable to those achieved with commercially available LIP3000. Moreover, COE-S6/siRNA nanocomplexes enabled efficient silencing of the K-ras gene in pancreatic cancer cells and significant inhibition of cancer tumor growth with negligible in vitro toxicities. More importantly, cell invasion and colony formation of the Panc-1 cells were significantly inhibited, and apoptosis of the pancreatic cancer cells was also promoted. We also note that COE-S6 is much less toxic relative to commercial lipid formulations, and it provides optical signatures that can enable subsequent mechanistic work without the need to label nucleotides. COE-S6-based nanoplexes are thus a promising candidate as nonviral vectors for gene delivery.

Primary duct closure versus T-tube drainage after laparoscopic common bile duct exploration: a meta-analysis.

BACKGROUND AND AIMS: Laparoscopic common bile duct exploration (LCBDE) is considered a safe and effective method for the removal of bile duct stones. However, the choice of primary duct closure (PDC) or T-tube drainage (TTD) technique after LCBDE is still controversial. This study aimed to compare the safety and effectiveness of PDC and TTD after LCBDE. METHODS: Studies published before May 1, 2021 in PubMed, Web of Science, and Cochrane Library databases were searched to screen out randomized controlled trials (RCTs) and cohort studies to compare PDC with TTD. Meta-analyses of fixed effect and random effect models were performed using RevMan 5.3. RESULTS: A total of 1865 patients were enrolled in six RCTs and ten cohort studies. Regarding RCTs, the PDC group was significantly better than the TTD group in terms of operation time, total postoperative complications, postoperative hospital stay, and hospitalization expenses (all P<0.05). Based on cohort studies of the subgroup, the PDC group had shorter operation time, shorter postoperative hospital stay, less intraoperative blood loss, and limited total postoperative complications. Statistically, there were no significant differences in bile leakage, retained stones, stone recurrence, bile duct stricture, postoperative pancreatitis, other complications, or postoperative exhaust time between the TTD and PDC groups. CONCLUSIONS: Based on the available evidence, compared with TTD, PDC is safe and effective, and can be used as the first choice after transductal LCBDE in patients with choledocholithiasis.