Clinical sonochemotherapy of inoperable pancreatic cancer using diagnostic ultrasound and microbubbles: a multicentre, open-label, randomised, controlled trial.

OBJECTIVES: Sonochemotherapy, which uses microbubble (MB)-assisted ultrasound (US) to deliver chemotherapeutic agents, has the potential to enhance tumour chemotherapy. The combination of US and MB has been demonstrated to prolong the survival of patients with pancreatic cancer. This phase 2 clinical trial aimed to determine the clinical efficacy and safety of sonochemotherapy for inoperable pancreatic ductal adenocarcinoma by using US and MB. METHODS: Eighty-two patients with stage III or IV pancreatic cancer were recruited from July 2018 to March 2021 and followed up until September 2022. US treatment was performed with a modified diagnostic US scanner for 30 min after chemotherapeutic infusion. The primary endpoint was overall survival (OS), and the secondary endpoints were Eastern Cooperative Oncology Group (ECOG) status < 2, progression-free survival (PFS), disease control rate (DCR), and adverse events. RESULTS: Seventy-eight patients were randomly allocated (40 to chemotherapy and 38 to sonochemotherapy). The median OS was longer with sonochemotherapy than with chemotherapy (9.10 vs. 6.10 months; p = 0.037). The median PFS with sonochemotherapy was 5.50 months, compared with 3.50 months (p = 0.080) for chemotherapy. The time of ECOG status < 2 was longer with sonochemotherapy (7.20 months) than with chemotherapy (5.00 months; p = 0.029). The DCR was 73.68% for sonochemotherapy compared with 42.50% for the control (p = 0.005). The incidence of overall adverse events was balanced between the two groups. CONCLUSIONS: The use of sonochemotherapy can extend the survival and well-being time of stage III or IV pancreatic cancer patients without any increase in serious adverse events. TRIAL REGISTRATION: ChineseClinicalTrials.gov ChiCTR2100044721 CLINICAL RELEVANCE STATEMENT: This multicentre, randomised, controlled trial has proven that sonochemotherapy, namely, the combination of diagnostic ultrasound, microbubbles, and chemotherapy, could extend the overall survival of patients with end-stage pancreatic ductal adenocarcinoma from 6.10 to 9.10 months without increasing any serious adverse events. KEY POINTS: • This is the first multicentre, randomised, controlled trial of sonochemotherapy for clinical pancreatic cancer treatment using ultrasound and a commercial ultrasound contrast agent. • Sonochemotherapy extended the median overall survival from 6.10 (chemotherapy alone) to 9.10 months. • The disease control rate increased from 42.50% with chemotherapy to 73.68% with sonochemotherapy.

Kidney transplantation from donors with Marfan syndrome: report of 2 cases and literature review / 器官移植

Objective To investigate the feasibility and clinical experience of kidney transplantation from donors with Marfan syndrome (MFS). Methods Clinical data of 2 recipients undergoing kidney transplantation from the same MFS patient were retrospectively analyzed and literature review of 2 cases was conducted. Characteristics and clinical diagnosis and treatment of kidney transplantation from MFS patients were summarized. Results The Remuzzi scores of the left and right donor kidneys of the MFS patient during time-zero biopsy were 1 and 2. No significant difference was observed in the renal arteriole wall compared with other donors of brain death and cardiac death. Two recipients who received kidney transplantation from the MFS patient suffered from postoperative delayed graft function. After short-term hemodialysis, the graft function of the recipients received the left and right kidney began to gradually recover at postoperative 10 d and 20 d. After discharge, serum creatinine level of the recipient received the left kidney was ranged from 80 to 90 μmol/L, whereas that of the recipient received the right kidney kept declining, and the lowest serum creatinine level was 232 μmol/L before the submission date (at postoperative 43 d). Through literature review, two cases successfully undergoing kidney transplantation from the same MFS donor were reported. Both two recipients experienced delayed graft function, and then renal function was restored to normal. Until the publication date, 1 recipient has survived for 6 years, and the other recipient died of de novo cerebrovascular disease at postoperative 2 years. Conclusions MFS patients may serve as an acceptable source of kidney donors. However, the willingness and general conditions of the recipients should be carefully evaluated before kidney transplantation. Intraoperatively, potential risk of tear of renal arterial media should be properly treated. Extensive attention should be paid to the incidence of postoperative complications.

Tumor cell-derived exosomes mediating hsa_circ_0001739/lncRNA AC159540.1 facilitate liver metastasis in colorectal cancer.

BACKGROUND: The current study probed into how tumor cell-derived exosomes (Exos) mediated hsa_circ_0001739/lncRNA AC159540.1 to manipulate microRNA (miR)-218-5p/FTO-N6-methyladenosine (m6A)/MYC signal axis in liver metastasis in colorectal cancer (CRC). METHODS: hsa_circ_0001739 and lncRNA AC159540.1 were identified as the upstream regulator of miR-218-5p using ENCORI and LncBase databases. Expression patterns of miR-218-5p, hsa_circ_0001739, lncRNA AC159540.1, FTO, and MYC were detected, accompanied by loss-and-gain-of function assays to examine their effects on CRC cell biological functions. SW480 cells-derived Exos were purified, followed by in vitro studies to uncover the effect of hsa_circ_0001739/lncRNA AC159540. RESULTS: miR-218-5p was downregulated while hsa_circ_0001739/lncRNA AC159540.1 was upregulated in CRC tissues and cells. Silencing of hsa_circ_0001739/lncRNA AC159540.1 restrained the malignant phenotypes of CRC cells. Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 competitively inhibited miR-218-5p to elevate FTO and MYC. The inducing role of Exos-mediated hsa_circ_0001739/lncRNA AC159540.1 in CRC was also validated in vivo. CONCLUSION: Conclusively, Exos-mediated circ_0001739/lncRNA AC159540.1 regulatory network is critical for CRC, offering a theoretical basis for CRC treatment.

Contrast-enhanced ultrasound liver imaging reporting and data system v2017: patient outcomes after treatment for early-stage hepatocellular carcinoma nodules with category 3-5 and category M.

OBJECTIVE: To evaluate correlation between contrast-enhanced ultrasonography Liver Imaging Reporting and Data System (CEUS LI-RADS; v. 2017) categories (LR 3-5 vs LR-M) and outcomes in patients with early-stage hepatocellular carcinoma (HCC) after initial therapy. METHODS: In this retrospective study, 272 patients with high risks for HCC and solitary clinically or pathologically confirmed HCC were identified between January 2010 and December 2015. Patients were initially treated by resection and radiofrequency ablation (RFA) according to the Barcelona Clinic Liver Cancer staging system and were followed up until December 31, 2018. Recurrence-free survival (RFS) and overall survival (OS) were compared between nodules assigned as LR 3-5 or LR M according to CEUS LI-RADS v. 2017 by using the Kaplan-Meier curve, log-rank test, and Cox proportional hazard model. RESULTS: Early washout is the key determinating whether a nodule is classed as LR-M. Treatment procedures and LI-RADS category showed an independent correlation with OS and RFS (p < 0.05). LR 3-5 category were more correlated with better OS (88.6 months and 74.2 months, respectively; p = 0.017) compared with LR-M. Surgical resection demonstrated longer OS and RFS than RFA in LR-M patients and longer OS in LR 3-5 patients (p < 0.05). Besides, there was no significantly difference in OS and RFS between two categories in resection (p > 0.05), while for patients treated with RFA, LR 3-5 patients showed significant longer OS and RFS than LR-M patients (p < 0.05). CONCLUSION: Patients with HCC assigned as LR-M showed worse RFS and OS and surgical resection tended to be a more effective treatment for these patients. ADVANCES IN KNOWLEDGE: Putting forward a theory that CEUS LI-RADS categories could independently predict the outcome for patients with solitary HCC at early-stage after initial treatment.

Research progress on the role of macrophages in renal allograft fibrosis / 器官移植

Ischemia-reperfusion injury, rejection, nephrotoxicity caused by calcineurin inhibitors and other factors cause excessive accumulation of renal extracellular matrix after kidney transplantation, which gradually induce renal fibrosis and eventually lead to renal failure. In recent years, the mechanism of macrophages in renal allograft fibrosis has gradually captivated widespread attention. Studies have shown that some drugs like mammalian target of rapamycin inhibitors may mitigate renal allograft fibrosis through the macrophage. In this article, the main pathogenesis and pathophysiological mechanism of renal allograft fibrosis, the role of different macrophages in the progression of renal allograft fibrosis, the infiltration of peripherally-recruited macrophages and renal resident macrophages into renal injury areas, the induction of myofibroblasts by macrophages and potential treatment regimens of macrophage-associated renal allograft fibrosis were reviewed, aiming to provide reference for investigating the role of macrophages in renal allograft fibrosis.

Primary hyperoxaluria type II and organ transplantation / 器官移植

Primary hyperoxaluria type Ⅱ (PH2) is an inherited disorder of the glyoxylate metabolism caused by the gene mutation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR). PH2 is characterized by recurrent nephrolithiasis and nephrocalcinosis, which may even progress into end-stage renal disease. Currently, organ transplantation is the only treatment option for PH2, which mainly includes two strategies: kidney transplantation and combined liver and kidney transplantation. Kidney transplantation yields a high risk of recurrence of oxalate nephropathy, which may cause early graft dysfunction. Combined liver and kidney transplantation could mitigate the deficiency of oxalate metabolism, whereas it yields a high risk of graft complications. PH2 is an extremely rare disorder. No consensus has been reached on the indications, surgical selection and perioperative management of organ transplantation for PH2 patients. In this article, the pathogenesis, diagnosis, monitoring and organ transplantation experience of PH2 were reviewed, aiming to divert clinicians' attention to PH2 and provide reference for determining diagnosis and treatment regimens, especially transplantation strategy for PH2 patients.

Application of ureteral stent in kidney transplantation / 器官移植

Ureteral stricture, urine leakage and other urinary complications are likely to occur after kidney transplantation, which severely affect the function of renal allograft and even lead to renal allograft loss. Ureteral stent plays a critical role in kidney transplantation, which could promote the urine flow from kidney to bladder after kidney transplantation, lower the pressure within the ureter and reduce the risk of early urinary complications. However, it may also cause urinary tract infection, stent-related complications and BK virus infection, etc. Therefore, clinicians should flexibly grasp the indications for ureteral stent removal. In this article, the application, potential adverse reactions and the timing of removal of ureteral stent in the field of kidney transplantation were reviewed, aiming to provide reference for clinical decision-making related to ureteral stent after kidney transplantation.

Research progress on the role of macrophages in post-transplantation chronic rejection / 器官移植

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, rejection remains an important factor affecting the allograft survival. At present, acute rejection may be effectively treated, whereas no effective interventions are available for post-transplantation chronic rejection. Long-term chronic rejection may lead to graft failure and severely affect long-term survival rate of allografts. In recent years, the role of macrophages in post-transplantation chronic rejection has gradually captivated increasing attention. In this article, main pathological changes of chronic rejection, the diversity and functional differences of macrophages involved in chronic rejection, and the role and mechanism of macrophages in chronic rejection were reviewed, and research progresses on macrophage-related treatment for chronic rejection were summarized, aiming to provide reference for the study of macrophages in post-transplantation chronic rejection.

Management of diarrhea after kidney transplantation / 器官移植

Diarrhea is a frequent complication after kidney transplantation, which is a common clinical manifestation of prevalent diseases following multiple types of organ transplantation. The common causes of diarrhea after kidney transplantation include adverse reactions of immunosuppressants, infectious diseases and de novo postoperative inflammatory bowel disease, etc. Diarrhea could seriously affect the quality of life of kidney transplant recipients, and may lead to allograft dysfunction or even death of recipients. Because the causes of diarrhea after kidney transplantation are complicated and probably overlap with each other, along with individual differences among recipients, the etiological diagnosis and targeted treatment of diarrhea after kidney transplantation should follow the principles of gradual and phased treatment. In this article, the epidemiology and harm, common causes and management strategies of diarrhea after kidney transplantation were summarized, aiming to deepen the clinicians' understanding and enhance the diagnosis and treatment levels of diarrhea after kidney transplantation, thereby improving the quality of life and prognosis of kidney transplant recipients.

Mitofusin 2 and ischemia-reperfusion injury / 器官移植

Mitochondria is one of the important organelles, which is composed of outer mitochondrial membrane and inner mitochondrial membrane. Mitochondrial structure and function are regulated by mitochondrial dynamics. Mitochondrial fusion- and fission-related proteins may participate in the process of mitochondrial fusion and fission, mediate mitochondrial dynamics, thereby regulating cell structure, function and energy metabolism. Mitofusin (MFN) 2, a protein located on the outer mitochondrial membrane of mammalian, has guanosine triphosphatase activity, which may mediate mitochondrial fusion, participate in mitophagy, formation of mitochondria-associated endoplasmic reticulum membrane and apoptosis, and significantly affect the incidence and development of ischemia-reperfusion injury (IRI). In this article, the structure, regulation, function of MFN2 and its role in IRI were reviewed, and the relationship between MFN2 and IRI and underlying mechanism were investigated, aiming to provide novel targets and ideas for the prevention and treatment of IRI.

Research progress on application of shear wave elastography in kidney transplantation / 器官移植

Early detection of renal allograft dysfunction plays a critical role in the management of immunosuppression and the survival of renal allograft. However, early detection of renal allograft dysfunction still has certain challenges because no significant changes could be observed in clinical manifestations and biochemical parameters during the early stage. As a novel ultrasound examination tool in recent years, shear wave elastography has been successfully applied in the detection of thyroid, breast, liver and alternative organs. In addition, it also has promising application prospect in the examination of renal allograft due to multiple advantages of real-time, dynamic, accuracy and repeatability. In this article, the classification, principle, advantages, influencing factors of shear wave elastography and its application in the field of kidney transplantation were reviewed, aiming to provide reference for clinicians to make accurate decisions in the prevention and monitoring of renal allograft diseases.

Preoperative Evaluation of Central Lymph Nodes in Papillary Thyroid Carcinoma Using High-Resolution Ultrasound and Shear-Wave Elastography.

ABSTRACT: The aim of this study was to discuss the diagnostic value of high-resolution ultrasound and virtual touch tissue imaging quantification (VTIQ) for distinguishing metastatic and benign central lymph nodes (CLNs) in patients with papillary thyroid carcinoma. This retrospective study involved 86 pathologically proven benign lymph nodes (LNs) and 118 metastatic LNs in patients with papillary thyroid carcinoma. We analyzed the sonographic features of CLNs (size, shape, distribution, hilum, echogenicity, cystic change, calcification, vascularity, shear-wave velocity [SWV]). The prevalence of sonographic features and the SWV was compared between metastatic and benign CLNs. The size, shape, margin, distribution, presence of hilum, echogenicity, calcification, and vascularity were significantly different between benign and metastatic CLNs (P < 0.05 for all). The mean maximum SWV for malignant CLNs was 3.139 ± 0.408 m/s, whereas that of benign CLNs was 2.418 ± 0.369 m/s (P < 0.05). The cutoff point of the SWV for differentiating benign and malignant LNs was 2.675 m/s. Logistic regression analysis showed that round or irregular shape, aggregation or fusion, calcification, and VTIQ value greater than 2.675 m/s of CLNs were independent risk factors for malignancy, with an odds ratio of 5.77, 3.05, 3.23, and 62.85, respectively. High-resolution ultrasound and VTIQ can provide valuable information for distinguishing metastatic from benign CLNs.

Edaravone attenuates cadmium-induced toxicity by inhibiting oxidative stress and inflammation in ICR mice.

The neurotoxicity caused by cadmium (Cd) is well known in humans and experimental animals. However, there is no effective treatment for its toxicity. In this study, we established Cd toxicity models in cultured cells or mice to investigate the detoxification effect of edaravone (Eda). We found that Eda protected GL261 cells from Cd toxicity and prevented the loss of cell viability. In Cd-exposed mice, liver, kidney and testicular damage, as well as cognitive dysfunction were observed. Oxidative stress and inflammatory responses, such as decreased SOD and CAT, increased LDH and MDA, and abnormal changes in the inflammatory factors TNF-α, IL-1ß, IL-6 and IL-10 were detected in serum and brain tissue. Eda protected mice from Cd-induced toxicity and abrogated oxidative stress and inflammatory responses. Also, Eda prevented inflammatory activation of microglia and astrocytes and was accompanied by restoration of the neuronal marker protein MAP2, indicating restoration of neuronal function. In addition, the BDNF-TrkB/Akt and Notch/HES-1 signaling axes were involved in the response of Eda to the elimination of Cd toxicity. In conclusion, Eda does contribute to the clearance of Cd-induced toxicity.

sMicroRNA-28-5p acts as a metastasis suppressor in gastric cancer by targeting Nrf2.

The transcription factor nuclear factor (erythroid-2)-related factor 2 (Nrf2) can principally serve a mode of protection for both the normal cells and cancer cells from cellular stress, and elevates cancer cell survival. microRNA-28 (miR-28) has been involved in the regulation of Nrf2 expression in breast epithelial cells. However, no comprehensive analysis has been conducted regarding the function of miR-28-5p regulating Nrf2 in gastric cancer (GC). In this study, we aimed to evaluate their interaction and biological roles in the migration and invasion of GC cells. The expression of Nrf2 in the cancer tissues harvested from 42 patients with GC was examined by an array of molecular techniques comprising of Immunohistochemical staining, RT-qPCR and Western blot analysis. Kaplan-Meier method was adopted for analysis of the correlation of Nrf2 with the prognosis of GC patients. Interaction between miR-28-5p and Nrf2 was determined using the bioinformatics analysis and dual luciferase reporter gene assay. Gain- and loss-of-function studies of miR-28-5p and Nrf2 were conducted to elucidate their effects on GC cell migration, invasion and metastasis, as well as expression pattern of several epithelial-mesenchymal transition (EMT)-related proteins. Results indicated that the expression pattern of Nrf2 was significantly upregulated in GC tissues and indicative of poor prognosis of GC patients. miR-28-5p was verified to target Nrf2 and downregulate its expression. GC cells with overexpression of miR-28-5p or Nrf2 knockdown exhibited a marked reduction in the migrated and invasive abilities, along with the N-cadherin expression yet an increase of E-cadherin expression. Furthermore, miR-28-5p exerted an inhibitory function on the metastatic and tumorigenicity of GC cells. In conclusion, miR-28-5p is a comprehensive tumor suppressor that inhibits GC cell migration and invasion through repressing the Nrf2 expression. Therefore, miR-28-5p may serve as a potential biomarker for the prognosis of GC and a novel therapeutic target in advanced GC.

Value of dual-phase, contrast-enhanced CT combined with ultrasound for the diagnosis of metastasis to central lymph nodes in patients with papillary thyroid cancer.

AIMS: To evaluate the diagnostic performance of computed tomography combined with ultrasound (CT/US) in metastatic central lymph nodes (CLNs) compared with US in patients with papillary thyroid cancer (PTC). MATERIAL AND METHODS: Six-hundred patients with surgically proven PTC who underwent both US and CT examination before CLN dissection were evaluated retrospectively. All cases were divided into four subgroups according to the tumor size and number. Diagnostic performances of US, CT and CT/US were evaluated. RESULTS: Among 600 patients with CLN dissection, CT/US showed higher sensitivity (89.10%) and accuracy (83.00%) than US alone (76.06%, 76.50%). In the subgroup of solitary non-microcarcinomas, the AUC of CT/US was significantly higher than that for US alone (0.827 vs. 0.722, P < 0.05). For the subgroup of solitary or multiple microcarcinomas, the performance efficiency of CT had no obvious advantage over that of US (0.698 vs. 0.740, 0.798 vs. 0.802, P > 0.05). For the subgroup of multiple non-microcarcinomas, CT, US and US/CT had high diagnostic efficacy (AUC > 0.8, Accuracy >80%. P > 0.05), and there was no significant difference between them. CONCLUSIONS: In the subgroup of solitary non-microcarcinoma, CT combined with US provided better diagnostic efficacy, and for those cases, complementary CT examination was recommended. In other subgroups, the diagnostic efficacy of US/CT was similar to that of US alone, and there was no significant benefit from additional CT examination.

Development and validation of a nomogram for preoperative prediction of level VII nodal spread in papillary thyroid cancer: Radiologic-pathologic correlation.

PURPOSE: To develop and validate a diagnostic nomogram for preoperative prediction of the level VII nodal spread in papillary thyroid cancer (PTC) by incorporating CT features. METHODS: A dataset of 7896 patients experiencing thyroidectomy for thyroid cancer was collected retrospectively from two hospitals, and 300 patients were finally included in this study. The CT features of metastatic LN were extracted with a one by one match of radiologic-pathologic correlation. Multivariable binary logistic regression analysis was used to develop predicting model, and then a nomogram was developed utilizing a primary cohort of 152 patients from hospital #1. The nomogram was validated in external cohort of 62 patients from hospital #2 and an independent cohort of 86 patients from hospital #1. The performance of the nomogram was evaluated with respect to its calibration, discrimination. RESULTS: 531 LNs from 300 patients were analyzed. 42.6% LNs were > 5 mm in short diameter. A total of 7 selected CT features were significantly associated with LN status (P < 0.05), including nodular enhancement, cystic change, calcification and so on. These features were contained in the prediction nomogram. The model showed good discrimination and good calibration, with a C-index of 0.938 (95% CI, 0.913 to 0.963) and 0. 795 (95% CI, 0. 726 to 0.864) for the primary cohort and the validation cohort, respectively. Decision curve analysis demonstrated that the nomogram was clinically applicable. CONCLUSIONS: This nomogram incorporating pathologically relevant CT features has demonstrated a high diagnostic value for predicting level VII nodal spread in PTC. Our work may help thyroid surgeon to decide whether upper mediastinal lymphadenectomy should be performed, which is associated with thoracotomy or other surgery.

Intracapsular infection of polycystic kidney disease and renal transplantation / 器官移植

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic hereditary kidney disease, which can progress into end-stage renal disease (ESRD). Patients with ADPKD constantly suffer from recurrent intracapsular infection. The drug resistance caused by antibiotic treatment is becoming increasingly prominent. The pattern of renal transplantation should be selected according to the infection of polycystic kidney disease. In this article, the origin of renal cyst, classification and source of cystic fluid, type and drug resistance of bacteria in the cystic fluid, and intracapsular infection of patients with renal transplantation- associated ADPKD were reviewed, aiming to provide reference for the diagnosis and treatment of intracapsular infection of patients with ADPKD.