The second docetaxel rechallenge for metastatic castration-resistant prostate cancer: a case report.

Background: Docetaxel combined with prednisone plus androgen deprivation therapy (ADT) is the preferred treatment option for metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC). With the development of next-generation hormonal agents (NHAs) and poly (ADP-ribose) polymerase (PARP) inhibitors, more aggressive first-line or later-line treatment strategies have been added to the treatment of mHSPC and mCRPC. However, docetaxel rechallenge (DR) has special clinical significance in patients with "docetaxel-sensitive" prostate cancer. There are no reports on the efficacy and safety of the second DR in mCRPC patients. Case presentation: We report one patient diagnosed with mCRPC who showed progression-free survival (PFS) and overall survival (OS) benefits and safety and good lower urinary tract function after the second DR. Conclusion: The second DR as a potential alternative later-line treatment strategy should be considered for patients with mCRPC who worry about the high economic burden of multigene molecular testing and PARP inhibitors as well as repeated prostate needle biopsy.

The application of magnetic anchoring traction device in assisting donor liver bench surgery in classic orthotopic liver transplantation.

OBJECTIVE: To explore the clinical application of a newly developed magnetic anchoring traction (MAT) system in the liver bench trimming and transplantation surgery. BACKGROUND: The conventionally limited space, vision, and exposure have always been a challenge for the quality of surgery in the liver bench trimming due to the fact that the exposure depends largely on the experience of surgeon. To deal with this problem, a MAT system is developed as an alternative support to enhance exposure. The preliminarily experiments on animals verified its feasibility and reliability in the practical use, and its clinical application and effects were examined in the present research. METHODS: A total of 20 DCD (donation of cardiac death) donor livers were collected and divided evenly between the magnetic anchor traction (MAT) assisted group (n = 10) and the manual assisted group (n = 10). The results and quality assessment from experts about the liver bench surgery performed by two groups were examined and compared. RESULTS: The MAT system can be employed effectively to compete and replace the manual assistance to achieve a better exposure in the liver bench trimming. No statistical difference was found regarding the baseline data between the MAT and the manual groups. In the inferior vena cava and hepatic artery trimming, the MAT group outperformed the manual group remarkably in many aspects. The surgery time for liver bench shortened considerably after a quick grasp of MAT skills by surgeons. CONCLUSION: The MAT system provides a more stable, reliable and qualified local exposure in the liver bench surgery, and can preferably be employed to replace the manual assistance in the procedures of liver transplantation.

Antibacterial and Antifungal Properties of a Novel Antimicrobial Peptide GK-19 and Its Application in Skin and Soft Tissue Infections Induced by MRSA or Candida albicans.

The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.

Education curriculum for surgical interns that improves stress management and grit levels.

INTRODUCTION: Overwhelming stress or burnout has been observed in medical students, including 69% of surgical interns. This study aimed to assess the stress levels of fifth-year medical students during surgical training. An education curriculum with both clinical and research sessions was evaluated for its effect on the interns' stress and grit levels. METHOD: A blinded, prospective study was conducted to evaluate the efficacy of an educational program on the recognition and management of stress. The State-Trait Anxiety Inventory (STAI) was used to assess anxiety. The Grit Scale was used to quantify the interns' grit, conscientiousness, and self-control. RESULTS: The STAI survey results showed that the STAI state scores but not the trait scores were significantly lower in the intervention group than in the control group (p < 0.05). Additionally, the postintervention STAI score and the change in the STAI score were both lower in the intervention group (p < 0.05). There was a significant increase in grit among the medical students in the intervention group from baseline to post-intervention (p < 0.001). The scores of the consistency and perseverance subscales of the Grit Scale also increased significantly from baseline to post-intervention (both p < 0.001). CONCLUSION: The education curriculum can improve interns' stress management and grit levels. We believe this curriculum needs to be implemented in medical education, and we plan to continue the program.

A modified animal model of hepatic regeneration induced by hilar bile duct ligation.

Mechanisms of the proliferation of liver are mainly studied in animal model of liver regeneration after partial hepatectomy (PH). However, the PH model involves complex regeneration mechanisms, including hemodynamic factors, cytokines, growth factors, and metabolites. Among liver metabolites, bile acid (BA) is a key signaling molecule that regulates liver regeneration. This study aimed to establish a new type of rapid liver hyperplasia model induced mainly by bile acid pathway through hepatoenteral circulation with hilar bile duct ligation (HBDL). We first established the HBDL model by ligating the bile duct of all hepatic lobes but the right lateral lobe in rabbits and compared with the PVL model and sham operation group. Changes in the liver lobe and hemodynamics were observed. Liver function and the bile acid level were also analyzed. Then we verified the HBDL model in mice. Liver function and the levels of bile acids and cytokines were tested. The protein and mRNA levels of FXR, FGF15, CYP7A1 and FoxM1b in liver tissue were also analyzed. After hilar ligation of the biliary tract, the unligated liver lobes proliferated significantly. Compared with those in the sham group, the volume and weight of the unligated right lateral lobe of the liver in the HBDL group and the PVL group increased significantly (P < 0.05). Transient liver function impairment occurred both in the HBDL group and PVL group in the rabbit model as well as the mouse models. The bile acid levels in the HBDL groups of the rabbit model and mouse model increased significantly within first week after surgery (P < 0.05). The immunohistochemistry results confirmed the proliferation of hepatocytes in the unligated liver lobe. Compared with those in the sham group, the levels of FXR, FGF15 and FoxM1b in the HBDL group were significantly increased (P < 0.05), while the expression of CYP7A1 was inhibited. Compared with those in the HBDL group, the postoperative hemodynamic changes in the PVL group were significant (P < 0.05). The levels of IL-6 and TNF-α in the HBDL group were higher than those in the sham group. The HBDL model is simple to establish and exhibits good surgical tolerance. The model has definite proliferative effect and strong specificity of bile acid pathway. This is an ideal animal model to study the mechanism of liver regeneration through bile acid pathway.

NFATc1 promotes epithelial-mesenchymal transition and facilitates colorectal cancer metastasis by targeting SNAI1.

Metastatic recurrence remains a major cause of colorectal cancer (CRC) mortality. In this study, we investigated the mechanistic role of nuclear factor of activated T cells 1 (NFATc1) in CRC metastasis. First, we explored the potential role of NFATc1 in CRC using bioinformatics and hypothesized that NFATc1 might play different roles at different stages of CRC development. Then, we examined the relative expression of NFATc1 in 25 CRC tissues and adjacent normal tissues, and further analyzed the correlation between NFATc1 expression levels and clinical stages in 120 CRC patients. The role of NFATc1 in CRC metastasis and the molecular mechanisms were investigated in both in vitro and in vivo models. Our results showed that the expression of NFATc1 was increased in metastatic CRC tissues and positively associated with clinical stages (stage I vs. stage II, III or IV) of CRC. Overexpression of NFATc1 promoted CRC cell migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, SNAI1 was verified as the direct transcriptional target of NFATc1 and interacted with SLUG to promote EMT. Remarkably, our lung and liver metastasis mouse model demonstrated that NFATc1 overexpression accelerated CRC metastasis, and treatment with FK506, a calcineurin-NFAT pathway inhibitor, could suppress CRC metastasis in vivo. Taken together, our findings suggest that NFATc1 could transcriptionally activate SNAI1, which in turn interacts with SLUG to mediate EMT to promote CRC metastasis. Thus, making NFATc1 a promising therapeutic target in the treatment of metastatic CRC.

Construction and validation of a nomogram for predicting cancer-specific survival in hepatocellular carcinoma patients.

The prognosis of patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is a research hotspot. This study aimed to incorporate important factors obtained from SEER database to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of patients with HCC and ICC. We obtained patient data from SEER database. The nomogram was constructed base on six prognostic factors for predicting CSS rates in HCC patients. The nomogram was validated by concordance index (C-index), the receiver operating characteristic (ROC) curve and calibration curves. A total of 3227 patients diagnosed with HCC (3038) and ICC (189) between 2010 and 2015 were included in this study. The C-index of the nomogram for HCC patients was 0.790 in the training cohort and 0.806 in the validation cohort. The 3- and 5-year AUCs were 0.811 and 0.793 in the training cohort. The calibration plots indicated that there was good agreement between the actual observations and predictions. In conclusion, we constructed and validated a nomogram for predicting the 3- and 5-year CSS in HCC patients. We have confirmed the precise calibration and excellent discrimination power of our nomogram.

Acute and subacute effects of irreversible electroporation on normal common bile ducts in a rabbit model.

BACKGROUND/PURPOSE: This study aimed to evaluate the acute and subacute effects of irreversible electroporation (IRE) on normal common bile ducts (CBDs). METHODS: Cell susceptibility to IRE was assessed in vitro with cholangiocarcinoma and normal cell lines. The electric field and temperature distributions were evaluated with a two-dimensional simulation model of bile duct. In vivo bile duct IRE was performed in 28 adult rabbits. RESULTS: Different cells showed different susceptibility to the effect of IRE, cancer cell line HUCC-T1 was the least sensitive to IRE. Simulations predicted the distributions of electric field and temperature during the IRE process, and the maximum temperature of tissue was below 43℃. Complications were observed in 8/28 animals (biliary dilatation, n = 4; biliary stricture, n = 4) by postoperative days 7, 14, and 28. Histopathological analyses revealed complete cell death with bile duct wall integrity. Bile duct epithelial recovery was completed between post-IRE days 14-28. CONCLUSIONS: The normal CBD retains the lumen wall integrity following IRE with immediate periductal placement of the electrode. However, the risk of biliary dilatation and stricture is a reminder that the parameters of IRE need to be determined more precisely to ensure the treatment efficacy and reduce the risk of collateral damage.

Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.