Topological Regulating Bismuth Nano-Semiconductor for Immunogenic Cell Death-Mediated Sonocatalytic Hyperthermia Therapy.

Immunogenic cell death (ICD) can activate the body's immune system via dead cell antigens to achieve immunotherapy. Currently, small molecule drugs have been used for ICD treatment in clinical, however, how to precisely control the induced ICD while treating tumors is of great significance for improving therapeutic efficacy. Based on this, a sono/light dual response strategy to tumor therapy and activation of ICD is proposed. A topological synthesis method is used to obtain sulfur-doped bismuth oxide Bi2 O3-x Sx (BS) using BiF3 (BF) as a template through reduction and a morphology-controllable bismuth-based nano-semiconductor with a narrow bandgap is constructed. Under the stimulation of ultrasound, BS can produce reactive oxygen species (ROS) through the sonocatalytic process, which cooperates with BS to consume glutathione and enhance cellular oxidative damage, further inducing ICD. Due to the introduction of sulfur in the reduction reaction, BS can achieve photothermal conversion under light, and combine with ROS to treat tumors. Further, with the assistance of ivermectin (IVM) to form composite (BSM), combined with sono/light dual strategy, ICD is promoted and DCs maturation is accelerated. The proposed ICD-mediated hyperthermia/sonocatalytic therapy strategy will pay the way for synergetic enhancement of tumor treatment efficacy and provide a feasible idea for controllable induction of ICD.

A Novel Strategy for Rapid Fluorescence Detection of FluB and SARS-CoV-2.

Undoubtedly, SARS-CoV-2 has caused an outbreak of pneumonia that evolved into a worldwide pandemic. The confusion of early symptoms of the SARS-CoV-2 infection with other respiratory virus infections made it very difficult to block its spread, leading to the expansion of the outbreak and an unreasonable demand for medical resource allocation. The traditional immunochromatographic test strip (ICTS) can detect one analyte with one sample. Herein, this study presents a novel strategy for the simultaneous rapid detection of FluB/SARS-CoV-2, including quantum dot fluorescent microspheres (QDFM) ICTS and a supporting device. The ICTS could be applied to realize simultaneous detection of FluB and SARS-CoV-2 with one test in a short time. A device supporting FluB/SARS-CoV-2 QDFM ICTS was designed and had the characteristics of being safe, portable, low-cost, relatively stable, and easy to use, ensuring the device could replace the immunofluorescence analyzer in cases where there is no need for quantification. This device does not need to be operated by professional and technical personnel and has commercial application potential.

Laparoscopic Segmentectomy IV Using Hepatic Round Ligament Approach Combined with Fluorescent Negative Staining Method.

BACKGROUND: Laparoscopic segmentectomy, which maximizes the preservation of the functional hepatic reserve and the possibility for future repeat hepatectomy while ensuring adequate surgical margin, is a feasible alternative to hemihepatectomy for hepatocellular carcinoma (HCC) (Vigano et al. in Ann Surg 270(5):842-851, 2019, Ishizawa et al. in Ann Surg 256(6):959-964, 2012). Herein, we present a video of laparoscopic segmentectomy IV for HCC using hepatic round ligament approach combined with fluorescent negative staining method. PATIENT AND METHODS: A 44-year-old male with history of chronic hepatitis B virus (HBV) infection for 22 months was referred for treatment of a single HCC in segment IV. The procedure was performed according to the following steps: (1) lowering the hilar plate based on Laennec's capsule (Sugioka et al. in J Hepatobiliary Pancreat Sci 24(1):17-23, 2017) after cholecystectomy; (2) cutting the Glisson's pedicles to segment IV along the fissure for the round ligament; (3) the first parenchyma transection was along the falciform ligament, while cutting some deep pedicles to segment IV; (4) clamping the left Glisson's pedicle and using fluorescent negative staining method (Abo et al. in Eur J Surg Oncol 41(2):257-264, 2015, Funamizu et al. in J Hepatobiliary Pancreat Sci, 2021, Xu et al. in Surg Endosc 34(10):4683-4691, 2020); (5) the second parenchyma transection was performed along the boundary of negative fluorescence region to expose the middle hepatic vein (MHV) using a combination of cranial and caudal approaches. RESULTS: The operative time was 190 min, and blood loss during operation was 80 mL. The histopathologic examination showed a solitary HCC, 2.5 cm in diameter, with negative surgical margin and no microvascular invasion. The patient had an uneventful postoperative recovery and was discharged on postoperative day 5. CONCLUSION: The round ligament approach combined with fluorescent negative staining method for laparoscopic anatomic segmentectomy IV is a feasible and effective technique.

Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Hepatic Resection Alone for Selected Patients with Moderately Advanced Multifocal Hepatocellular Carcinomas.

BACKGROUND: The role of hepatic resection (HR) combined with radiofrequency ablation (RFA) versus HR alone remains unclear for patients with multifocal hepatocellular carcinomas (HCCs). The aim of this study was to assess the outcomes of selected patients with moderately advanced multifocal HCCs after HR combined with intraoperative RFA versus HR alone. METHODS: A total of 304 selected patients with multifocal HCCs (three or fewer lesions, with the largest lesion > 4.5 cm and the residual lesion[s] ≤ 3 cm) who underwent HR plus RFA (HR+RFA group) or HR alone (HR group) were included. Propensity score matching (PSM) was used to adjust for baseline differences. Multivariable and subgroup analyses estimated the effects of clinical factors on survival. RESULTS: Both overall survival (OS) and recurrence-free survival (RFS) were comparable between both groups before and after PSM. Subgroup analysis showed that HR was associated with better RFS than HR+RFA for those patients with two tumors, or with all lesions located in the same lobe or without microvascular invasion (MVI) [all p < 0.05]. Moreover, en bloc resection provided a higher RFS than separate resection for those with all lesions in the same lobe (p = 0.039). CONCLUSION: For selected patients with moderately advanced multifocal HCCs, HR+RFA may offer similar OS and RFS as HR alone. However, HR may be more suitable for those with two tumors, or with all lesions in the same lobe or without MVI. Moreover, en bloc resection may be recommended for those with all lesions in the same lobe.

Laparoscopic anatomic bi-segmentectomy (S3 and S4b) using the Glisson's pedicle-first and intrahepatic anatomic markers approach.

BACKGROUND: With the advancement of laparoscopic technology, more precise anatomical hepatectomies such as segmentectomy or even bi-segmentectomy have been recommended by updated expert consensus to treat a single small hepatocellular carcinoma (HCC) [1, 2]. Herein, we presented a video of laparoscopic anatomic bi-segmentectomy (S3 and S4b) using the Glisson's pedicle-first and intrahepatic anatomic markers approach. METHODS: A 66-year-old male was referred for treatment of a single HCC adjacent to the Sagittal part of the left portal vein. The procedure was performed according to the following steps: (1) dissecting and transecting the Glisson's pedicle to S3 and S4b based on Laennec's capsule [3]; (2) identification of the ischemia boundary on the liver surface and confirming the presence of adequate surgical margins within the boundary, ensuing the integrity of segment 2 and 4a by the intraoperative ultrasonography meanwhile; (3) the left parenchymal transection was begun along the demarcation line, exposing the Glisson's pedicle to S2, left hepatic vein, and umbilical fissure vein; (4) the right parenchymal transection was performed to expose the V5, V4b, and V4a. And this operation was approved by the Institutional Review Board of the West China Hospital and written informed consent was obtained from patient of Sichuan University and written informed consent was obtained from patient. (5) The blood supply of residual liver surface was observed, and the integrity of segment 2 and 4a hepatic pedicle was ensured by intraoperative ultrasonography. RESULTS: The operative time was 224 min and blood loss during operation was 50 ml. The histopathologic examination showed a solitary HCC, 4 cm in diameter, with negative surgical margin and no microvascular invasion. The patient had an uneventful postoperative recovery and was discharged on postoperative day 5. CONCLUSION: Laparoscopic bi-segmentectomy (S3 and S4b) using the Glisson's pedicle-first and intrahepatic anatomic markers approach is feasible and effective. Its advantages lie in obtaining the benefits of anatomical hepatectomy, while maximizing the postoperative functional hepatic reserve [4-6].

[Inhibition of Autophagy Augments the Anticancer Activity of KPT-330 in Mantle Cell Lymphoma Cells].

OBJECTIVE: To investigate the influence of novel CRM1 inhibitor KPT-330 on the autophagy of mantle cell lymphoma (MCL) cells, and effect of KPT-330 on the prolifiration of MCL cells in the presence or absence of autophagy inhibitor. METHODS: CCK-8 assay was used to detect the effect of KPT-330 on MCL cell lines Z-138， Jeko-1， Granta-519， Rec-1. The effect of KPT-330 on autophagy features were determined by detecting acidic vesicular organelles (AVO) by MDC staining under fluorescence microscope and detecting protein expression of LC3B-II assessed by Western blot. Further combined application of lysosomal inhibitor Chloroquine (CQ) was used to observe its effect on the increase of LC3B-Ⅱ caused by KPT-330. CalcuSyn 2.0 software was used to detected the Combination index (CI) of KPT-330 combined with CQ. RESULTS: The proliferation of MCL cell lines （Z-138, Jeko-1, Grant-519, Rec-1） could be inhibited by KPT-330 in a dose-dependent manner (r =0.930, 0.946, 0.691, 0.968 respectively). The number of acidic vesicular organelles (AVO) and the expression of LC3B-II were increased in KPT-330 treated Jeko-1 and Granta-519 cells in a dose-dependent manner (r Jeko-1=0.993, r Granta-519=0.971). LC3B-II protein amounts still increased upon KPT-330 treatment with the existence of lysosomal inhibitor CQ in Jeko-1 and Granta-519 cells, which was higher than CQ or KPT-330 single drug group. The combination of KPT-330 and CQ produced the synergistic effects on cells proliferation inhibition with CalcuSyn 2.0 analysis. CONCLUSION: KPT-330 can inhibit MCL cell proliferation and induce autophagy. KPT-330 combined with autophagy inhibitor CQ could produce synergistic anti MCL effects, providing experimental basis for clinical combination therapy.

Air-Liquid Interface Microfluidic Monitoring Sensor Platform for Studying Autophagy Regulation after PM2.5 Exposure.

Undoubtedly, a deep understanding of PM2.5-induced tumor metastasis at the molecular level can contribute to improving the therapeutic effects of related diseases. However, the underlying molecular mechanism of fine particle exposure through long noncoding RNA (lncRNA) regulation in autophagy and, ultimately, lung cancer (LC) metastasis remains elusive; on the other hand, the related monitoring sensor platform used to investigate autophagy and cell migration is lacking. Herein, this study performed an air-liquid interface microfluidic monitoring sensor (AIMMS) platform to analyze human bronchial epithelial cells after PM2.5 stimulation. The multiomics analysis [RNA sequencing (RNA-seq) on lncRNA and mRNA expressions separately] showed that MALAT1 was highly expressed in the PM2.5 treatment group. Furthermore, RNA-seq analysis demonstrated that autophagy-related pathways were activated. Notably, the main mRNAs associated with autophagy regulation, including ATG4D, ATG12, ATG7, and ATG3, were upregulated. Inhibition or downregulation of MALAT1 inhibited autophagy via the ATG4D/ATG12/ATG7/ATG3 pathway after PM2.5 exposure and ultimately suppressed LC metastasis. Thus, based on the AIMMS platform, we found that MALAT1 might become a promising therapeutic target. Furthermore, this low-cost AIMMS system as a fluorescence sensor integrated with the cell-monitor module could be employed to study LC migration after PM2.5 exposure. With the fluorescence cell-monitoring module, the platform could be used to observe the migration of LC cells and construct the tumor metastasis model. In the future, several fluorescence probes, including nanoprobes, could be used in the AIMMS platform to investigate many other biological processes, especially cell interaction and migration, in the fields of toxicology and pharmacology.

Laparoscopic Hepatectomy for Giant Hepatic Hemangioma Using the Involved Intrahepatic Anatomic Markers Approach.

BACKGROUND: Hepatic hemangioma has been one of the absolute indications of laparoscopic hepatectomy (LH).1 However, the risk of catastrophic intraoperative bleeding and the difficulty to control it make the laparoscopic treatment of giant hepatic hemangioma (GHH) a technical challenge for hepatobiliary surgeons.2 Herein, we presented a video of LH for GHH using the involved intrahepatic anatomic markers approach. METHODS: A 22-year-old female was referred for treatment of an intractable GHH (18 cm), which involved the left hepatic pedicle, left hepatic vein (LHV), and middle hepatic vein (MHV), resulting in the invisibility of the above intrahepatic anatomic markers on CT. The procedure was performed according to the following steps: (1) dissecting and ligating the left hepatic artery (LHA) and left portal vein (LPV) via intrafascial approach, respectively; (2) cutting the accessory LHA; (3) transecting parenchymal along the demarcation line in a caudal-to-cranial direction and exposing the involved caudal middle hepatic vein (MHV); (4) isolating and transecting the involved left hepatic duct; (5) preserving the integrity of involved MHV; (6) isolating and transecting the left hepatic vein (LHV) and splenic vein (SV); (7) mincing and extracting the specimen. This study was approved by the West China Hospital Ethics Committee and was conducted in accordance with the ethical guidelines of the Declaration of Helsinki. All treatments were performed after obtaining written informed consent from the patients. RESULTS: The operative time was 286 min, and blood loss during operation was 160 ml. This procedure ensured the integrity of MHV and maximized the residual functional hepatic volume. The histopathologic examination confirmed the hepatic cavernous hemangioma. The patient had an uneventful postoperative recovery and was discharged on the fifth day after operation. CONCLUSION: LH using the involved intrahepatic anatomic markers approach is feasible and effective for intractable GHH. Its advantages lie in decreasing the risk of disastrous hemorrhage or open conversion rate while maximizing the postoperative functional hepatic reserve.3.