Assessing the sensitivity and suitability of a range of detectors for SIMT PSQA.

PURPOSE: Single-isocenter multi-target intracranial stereotactic radiotherapy (SIMT) is an effective treatment for brain metastases with complex treatment plans and delivery optimization necessitating rigorous quality assurance. This work aims to assess five methods for quality assurance of SIMT treatment plans in terms of their suitability and sensitivity to delivery errors. METHODS: Sun Nuclear ArcCHECK and SRS MapCHECK, GafChromic EBT Radiochromic Film, machine log files, and Varian Portal Dosimetry were all used to measure 15 variations of a single SIMT plan. Variations of the original plan were created with Python. They comprised various degrees of systematic MLC offsets per leaf up to 2 mm, random per-leaf variations with differing minimum and maximum magnitudes, simulated collimator, and dose miscalibrations (MU scaling). The erroneous plans were re-imported into Eclipse and plan-quality degradation was assessed by comparing each plan variation to the original clinical plan in terms of the percentage of clinical goals passing relative to the original plan. Each erroneous plan could be then ranked by the plan-quality degradation percentage following recalculation in the TPS so that the effects of each variation could be correlated with γ pass rates and detector suitability. RESULTS & CONCLUSIONS: It was found that 2%/1 mm is a good starting point for the ArcCHECK, Portal Dosimetry, and the SRS MapCHECK methods, respectively, and provides clinically relevant error detection sensitivity. Looser dose criteria of 5%/1 mm or 5%/1.5 mm are suitable for film dosimetry and log-file-based methods. The statistical methods explored can be expanded to other areas of patient-specific QA and detector assessment.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay.

Detection and subtyping of hepatic echinococcosis from plain CT images with deep learning: a retrospective, multicentre study.

BACKGROUND: Hepatic echinococcosis is a severe endemic disease in some underdeveloped rural areas worldwide. Qualified physicians are in short supply in such areas, resulting in low rates of accurate diagnosis of this condition. In this study, we aimed to develop and evaluate an artificial intelligence (AI) system for automated detection and subtyping of hepatic echinococcosis using plain CT images with the goal of providing interpretable assistance to radiologists and clinicians. METHODS: We developed EDAM, an echinococcosis diagnostic AI system, to provide accurate and generalisable CT analysis for distinguishing hepatic echinococcosis from hepatic cysts and normal controls (no liver lesions), as well as subtyping hepatic echinococcosis as alveolar or cystic echinococcosis. EDAM includes a slice-level prediction model for lesion classification and segmentation and a patient-level diagnostic model for patient classification. We collected a plain CT database (n=700: 395 cystic echinococcosis, 122 alveolar echinococcosis, 130 hepatic cysts, and 53 normal controls) for developing EDAM, and two additional independent cohorts (n=156) for external validation of its performance and generalisation ability. We compared the performance of EDAM with 52 experienced radiologists in diagnosing and subtyping hepatic echinococcosis. FINDINGS: EDAM showed reliable performance in patient-level diagnosis on both the internal testing data (overall area under the receiver operating characteristic curve [AUC]: 0·974 [95% CI 0·936-0·994]; accuracy: 0·952 [0·939-0·965] for cystic echinococcosis, 0·981 [0·973-0·989] for alveolar echinococcosis; sensitivity: 0·966 [0·951-0·979] for cystic echinococcosis, 0·944 [0·908-0·970] for alveolar echinococcosis) and the external testing set (overall AUC: 0·953 [95% CI 0·840-0·973]; accuracy: 0·929 [0·915-0·947] for cystic echinococcosis, 0·936 [0·919-0·950] for alveolar echinococcosis; sensitivity: 0·913 [0·879-0·944] for cystic echinococcosis, 0·868 [0·841-0·897] for alveolar echinococcosis). The sensitivity of EDAM was robust across images from different CT manufacturers. EDAM outperformed most of the enrolled radiologists in detecting both alveolar echinococcosis and cystic echinococcosis. INTERPRETATION: EDAM is a clinically applicable AI system that can provide patient-level diagnoses with interpretable results. The accuracy and generalisation ability of EDAM demonstrates its potential for clinical use, especially in underdeveloped areas. FUNDING: Project of Qinghai Provincial Department of Science and Technology of China, National Natural Science Foundation of China, and Tsinghua-Fuzhou Institute of Data Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Spheroid on-demand printing and drug screening of endothelialized hepatocellular carcinoma model at different stages.

Hepatocellular carcinoma (HCC) poses a significant threat to human health and medical care. Its dynamic microenvironment and stages of development will influence the treatment strategies in clinics. Reconstructing tumor-microvascular interactions in different stages of the microenvironment is an urgent need forin vitrotumor pathology research and drug screening. However, the absence of tumor aggregates with paracancerous microvascular and staged tumor-endothelium interactions leads to bias in the antitumor drug responses. Herein, a spheroid-on-demand manipulation strategy was developed to construct staged endothelialized HCC models for drug screening. Pre-assembled HepG2 spheroids were directly printed by alternating viscous and inertial force jetting with high cell viability and integrity. A semi-open microfluidic chip was also designed to form a microvascular connections with high density, narrow diameter, and curved morphologies. According to the single or multiple lesions in stages Ⅰ or Ⅰ HCC, endothelialized HCC models from micrometer to millimeter scale with dense tumor cell aggregation and paracancerous endothelial distribution were successively constructed. A migrating stage Ⅰ HCC model was further constructed under TGF-ßtreatment, where the spheroids exhibited a more mesenchymal phenotype with a loose cell connection and spheroid dispersion. Finally, the stage ⅠHCC model showed stronger drug resistance compared to the stage Ⅰ model, while the stage III showed a more rapid response. The corresponding work provides a widely applicable method for the reproduction of tumor-microvascular interactions at different stages and holds great promise for the study of tumor migration, tumor-stromal cell interactions, and the development of anti-tumor therapeutic strategies.

Kidney transcriptome and cystic kidney disease genes in zebrafish.

Introduction: Polycystic kidney disease (PKD) is a condition where fluid filled cysts form on the kidney which leads to overall renal failure. Zebrafish has been recently adapted to study polycystic kidney disease, because of its powerful embryology and genetics. However, there are concerns on the conservation of this lower vertebrate in modeling polycystic kidney disease. Methods: Here, we aim to assess the molecular conservation of zebrafish by searching homologues polycystic kidney disease genes and carrying transcriptome studies in this animal. Results and Discussion: We found that out of 82 human cystic kidney disease genes, 81 have corresponding zebrafish homologs. While 75 of the genes have a single homologue, only 6 of these genes have two homologs. Comparison of the expression level of the transcripts enabled us to identify one homolog over the other homolog with >70% predominance, which would be prioritized for future experimental studies. Prompted by sexual dimorphism in human and rodent kidneys, we studied transcriptome between different sexes and noted significant differences in male vs. female zebrafish, indicating that sex dimorphism also occurs in zebrafish. Comparison between zebrafish and mouse identified 10% shared genes and 38% shared signaling pathways. String analysis revealed a cluster of genes differentially expressed in male vs. female zebrafish kidneys. In summary, this report demonstrated remarkable molecular conservation, supporting zebrafish as a useful animal model for cystic kidney disease.

Using Zebrafish Animal Model to Study the Genetic Underpinning and Mechanism of Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (Danio rerio), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.

Radiation therapy induces immunosenescence mediated by p90RSK.

Radiation therapy (RT) to the chest increases the patients' risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67-/DNMT3a+naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27-) and CD8+ effector memory CD45RA T cells (TEMRA). In vitro, we found the critical role of p90RSK activation in upregulating (1) CD38+/T-bet+ memory and naïve B, and myeloid cells, (2) senescence-associated ß-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence.

Genetic therapy in a mitochondrial disease model suggests a critical role for liver dysfunction in mortality.

The clinical and largely unpredictable heterogeneity of phenotypes in patients with mitochondrial disorders demonstrates the ongoing challenges in the understanding of this semi-autonomous organelle in biology and disease. Previously, we used the gene-breaking transposon to create 1200 transgenic zebrafish strains tagging protein-coding genes (Ichino et al., 2020), including the lrpprc locus. Here, we present and characterize a new genetic revertible animal model that recapitulates components of Leigh Syndrome French Canadian Type (LSFC), a mitochondrial disorder that includes diagnostic liver dysfunction. LSFC is caused by allelic variations in the LRPPRC gene, involved in mitochondrial mRNA polyadenylation and translation. lrpprc zebrafish homozygous mutants displayed biochemical and mitochondrial phenotypes similar to clinical manifestations observed in patients, including dysfunction in lipid homeostasis. We were able to rescue these phenotypes in the disease model using a liver-specific genetic model therapy, functionally demonstrating a previously under-recognized critical role for the liver in the pathophysiology of this disease.

Comparison of amphotericin B deoxycholate in combination with either flucytosine or fluconazole, and voriconazole plus flucytosine for the treatment of HIV-associated cryptococcal meningitis: a prospective multicenter study in China.

BACKGROUND: The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. METHODS: A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. RESULTS: Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p < 0.05 for both comparisons). However, the differences in CSF culture sterility and mortality between the VCZ + 5FC group and the AmB-D + 5FC group were not statistically significant. VCZ plus 5FC had a significantly advantageous effect on the incidence of new AIDS-defining illness and length of hospital stay, compared with AmB-D plus 5FC. Laboratory adverse events (grade 3 or 4), such as severe anemia, were less frequent with VCZ + 5FC use than with AmB-D combined with 5FC or Flu use. CONCLUSION: Our results suggest that AmB-D combined with 5FC remains the more efficacious induction regimen compared to AmB-D plus Flu, and that VCZ + 5FC might be a potential alternative when the standard regimen is not readily available, accessible, tolerated, or effective. CLINICAL TRIALS: Registration number, ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

Advances in the pharmacological treatment of hepatic alveolar echinococcosis: From laboratory to clinic.

Hepatic alveolar echinococcosis (HAE) is a zoonotic parasitic disease caused by the larvae of Echinococcus multilocularis. Because of its characteristics of diffuse infiltration and growth similar to tumors, the disability rate and mortality rate are high among patients. Although surgery (including hepatectomy, liver transplantation, and autologous liver transplantation) is the first choice for the treatment of hepatic alveolar echinococcosis in clinic, drug treatment still plays an important and irreplaceable role in patients with end-stage echinococcosis, including patients with multiple organ metastasis, patients with inferior vena cava invasion, or patients with surgical contraindications, etc. However, Albendazole is the only recommended clinical drug which could exhibit a parasitostatic rather than a parasitocidal effect. Novel drugs are needed but few investment was made in the field because the rarity of the cases. Drug repurposing might be a solution. In this review, FDA-approved drugs that have a potential curative effect on hepatic alveolar echinococcosis in animal models are summarized. Further, nano drug delivery systems boosting the therapeutic effect on hepatic alveolar echinococcosis are also reviewed. Taken together, these might contribute to the development of novel strategy for advanced hepatic alveolar echinococcosis.

A missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish.

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that developed hepatic cysts during larval stages. The cyst formation was not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed a disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene, which encodes a proprotein convertase. The mutation altered Furinb localization and caused endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant liver also exhibited increased mammalian target of rapamycin (mTOR) signaling. Treatment with mTOR inhibitors halted cyst formation at least partially through reducing ER stress. Conclusion: Our study has established a vertebrate model for studying hepatic cystogenesis and illustrated the contribution of ER stress in the disease pathogenesis.

Genetic Susceptibility and Mechanisms Underlying the Pathogenesis of Anthracycline-Associated Cardiotoxicity.

Anthracyclines are chemotherapeutic agents widely used to treat a variety of cancers, and these drugs have revolutionized our management of cancer patients. The dose-dependent cardiotoxicity of anthracyclines, however, remains one of the leading causes of chemotherapy treatment-associated mortality in cancer survivors. Patient threshold doses leading to anthracycline-induced cardiotoxicity (AIC) are highly variable among affected patients. This variability is largely ascribed to genetic variants in individuals' genomes. Here, we briefly discuss the prevailing mechanisms underlying the pathogenesis of AIC, and then, we review the genetic variants, mostly identified through human genetic approaches and identified in cancer survivors. The identification of all genetic susceptibilities and elucidation of underlying mechanisms of AIC can help improve upfront risk prediction assessment for potentially severe cardiotoxicity disease and provide valuable insights into the understanding of AIC pathophysiology, which can be further leveraged to develop targeted pharmacogenetic therapies for those at high risk.

Scalable Formation of Highly Viable and Functional Hepatocellular Carcinoma Spheroids in an Oxygen-Permeable Microwell Device for Anti-Tumor Drug Evaluation.

For high-throughput anti-cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non-oxygen-permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)-based oxygen-permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver-related functions. In anti-cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem-cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor-A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non-oxygen-permeable plates, these spheroids can be used as a more favorable model for early-stage HCCs and be applied in high-throughput anti-cancer drug screening.

MVI-Mind: A Novel Deep-Learning Strategy Using Computed Tomography (CT)-Based Radiomics for End-to-End High Efficiency Prediction of Microvascular Invasion in Hepatocellular Carcinoma.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) directly affects a patient's prognosis. The development of preoperative noninvasive diagnostic methods is significant for guiding optimal treatment plans. In this study, we investigated 138 patients with HCC and presented a novel end-to-end deep learning strategy based on computed tomography (CT) radiomics (MVI-Mind), which integrates data preprocessing, automatic segmentation of lesions and other regions, automatic feature extraction, and MVI prediction. A lightweight transformer and a convolutional neural network (CNN) were proposed for the segmentation and prediction modules, respectively. To demonstrate the superiority of MVI-Mind, we compared the framework's performance with that of current, mainstream segmentation, and classification models. The test results showed that MVI-Mind returned the best performance in both segmentation and prediction. The mean intersection over union (mIoU) of the segmentation module was 0.9006, and the area under the receiver operating characteristic curve (AUC) of the prediction module reached 0.9223. Additionally, it only took approximately 1 min to output a prediction for each patient, end-to-end using our computing device, which indicated that MVI-Mind could noninvasively, efficiently, and accurately predict the presence of MVI in HCC patients before surgery. This result will be helpful for doctors to make rational clinical decisions.

Development and Validation of a Homemade and Low-Cost Three-Dimensional Laparoscopic Simulator for Novices.

Background: The aim of this study was to design a low-cost three-dimensional (3D) laparoscopic simulator and validate its training effectiveness. Materials and Methods: We designed a low-cost 3D laparoscopic simulator using magnifying glass and cardboard box. Thirty-two laparoscopic novices were randomly divided into 3D group and two-dimensional (2D) group. The 3D group was trained on 3D simulator four times with 24 hours interval, and the 2D group was trained on 2D simulator. Five standardized laparoscopic tasks were performed by novices in each training. In the second part, subjects were transferred to the opposite simulator for one test after 24 hours of the fourth training. The completing time and errors for each task were recorded to assess the construct validity of simulator. Finally, the face validity and the content validity were evaluated through a closed-ended questionnaire. Results: There was no significant difference between the two groups in demographic or psychometric variables (P > .05). Compared with the 2D group, novices using 3D simulator had a better performance in five laparoscopic tasks, including a faster completing time (P < .001) and lower errors during training (P < .05). Additionally, the increased laparoscopic skill involved with our 3D simulator could be transferred to subsequent performance in 2D simulator (P < .05). Meanwhile, the score of face validity and content validity in our 3D simulator was significantly higher than that in 2D simulator (P < .05). Conclusion: Our 3D laparoscopic simulator effectively improved laparoscopic skills of novice surgeons, suggesting that the low-cost 3D simulator had satisfactory performance to satisfy requirement for novice training.

Treatment of Complicated Hepatic Alveolar Echinococcosis Disease With Suspicious Lymph Node Remote Metastasis Near the Inferior Vena Cava-Abdominal Aorta: A Case Report and Literature Review.

Echinococcosis is a human-animal parasitic disease caused by Echinococcosis tapeworm larvae in humans. From a global perspective, it is mainly prevalent in the mid-high latitudes of the Northern Hemisphere, and it is a widespread infectious disease. Its form, host and release areas are slightly different. In clinical practice, Echinococcus granulosus (hepatic cystic echinococcosis) is the most common. Its growth mode is swelling growth and its metastasis is more common in implanted metastasis; However, hepatic alveolar echinococcosis (HAE) is rare. It has been reported that HAE can metastasize through the blood or lymph nodes, and its invasive growth pattern is known as "carcinoma". At this time, it may be accompanied by invasion of the portal vein and inferior vena cava(IVC)or metastasis to distant organs outside the liver (such as lung, brain, lymph nodes). Most patients are in the middle or late stages, making treatment complicated. World Health Organization guidelines recommend radical resection of HAE; However, there is no consensus on lymph node dissection. To date, there have been no reports of cases of HAE accompanied by inferior vena cava-para-abdominal aortic suspected lymph node metastasis and infection. This article reports a clinical case of a complex HAE treated by the surgical method of "middle liver resection + abdominal enlarged lymph node resection + inferior vena cava repair", and histological examination was performed to illustrate the differences in microscopic pathology of alveolar echinococcosis invading the liver and lymph nodes at different magnifications. This article reviews the relevant literature on HAE and derives the latest treatment methods for HAE to provide a reference for future clinical cases of similar alveolar echinococcosis and maximize the benefits of patients.

Therapeutic lumbar puncture and lumbar drainage: which is more effective for the management of intracranial hypertension in HIV patients with cryptococcal meningitis? Results of a prospective non-randomized interventional study in China.

OBJECTIVE: This study aimed to evaluate the effectiveness of therapeutic lumbar drainage (LD) compared to therapeutic lumbar puncture (LP) for the management of intracranial hypertension (ICH) among HIV-positive patients with cryptococcal meningitis (CM). METHODS: The study was a multicenter prospective non-randomized interventional clinical trial. One hundred and sixteen HIV-associated CM patients were identified who presented with ICH (≥250 mmH2O). The LP group comprised 76 cases, while the LD group consisted of 40 cases. We compared mortality, intracranial pressure (ICP) normalization rate, and clinical symptom remission at 10 weeks, between the two groups. RESULTS: The cumulative mortality at week 10 was 22.4% in the LP group and 20% in the LD group (p = .927), without any significant difference in mortality between the two groups. Improvement after treatment at 2-weeks, ICP normalization, and headache reversal event occurrence in the two groups showed no significant difference (p > .05). The incidence of CSF Cryptococcus clearance at two weeks in the LD group was significantly higher than in the LP group (p < .05). The frequency of invasive lumbar therapeutic procedures in the LP group during the first week was higher than that of the LD group (p < .05). Localized infection at the puncture site occurred more frequently in the LD group than in the LP group (p < .05). CONCLUSION: For HIV-positive CM patients with an elevated ICP, LD and LP are comparably effective and safe options to normalize ICP. LP increases the frequency of invasive lumbar therapeutic procedures but does not incur more risk of infection events at the puncture site, while LD may accelerate CSF Cryptococcus clearance but may induce more frequent localized infection. TRIAL REGISTRATION: This study was registered as one of 12 trials under a general project at the Chinese Clinical Trial Registry (ChiCTR1900021195).

MiR-369-5p inhibits the proliferation and migration of hepatocellular carcinoma cells by down-regulating HOXA13 expression.

MicroRNA (miRNA) is vital to the progression of hepatocellular carcinoma (HCC). Thereinto, miR-369-5p could yield assorted effects on various cancers, but there are few reports concerning the effect of miR-369-5p on HCC. Thus this study aimed to investigate the effect and mechanism of miR-369-5p in HCC. The data of miR-369-5p and HOXA13 expressions in liver hepatocellular carcinoma (LIHC) were analyzed by starBase, and then the miR-369-5p expression in HCC tissues and cells was detected by quantitative real-time PCR. Subsequently, miR-369-5p mimic was transfected into HCC cells and then its effects on cell activities were evaluated by cell counting kit-8, colony formation, wound healing, transwell assays, respectively. Expressions of epithelial-mesenchymal transition (EMT)-related genes were determined by western blot. The targeting relationship between miR-369-5p and HOXA13 was predicted by Targetscan and verified by dual-luciferase reporter assay. Pearson correlation test was used to analyze the correlation between HOXA13 and miR-369-5p. The above assays were experimented again to investigate the effects of HOXA13 on biological activity and EMT of HCC cells. MiR-369-5p expression was down-regulated and HOXA13 expression was up-regulated in LIHC. MiR-369-5p targeted HOXA13 and the expression of miR-369-5p was negatively correlated with the HOXA13 expression. MiR-369-5p inhibited the viability, proliferation, migration and invasion of HCC cells, increased E-cadherin level and decreased N-cadherin and Vimentin expressions. Concurrently, HOXA13 overexpression could counteract the effects of miR-369-5p on biological activity and EMT-related biomarkers of HCC cells. To conclude, miR-369-5p inhibits the viability, proliferation, migration and invasion of HCC cells by repressing the expression of HOXA13.