Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

Modified duct-to-mucosa versus conventional pancreaticoenterostomy for pancreaticoduodenectomy: a retrospective cohort study based on propensity score matching analysis.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common neopathy after pancreatoduodenectomy (PD). An ideal pancreaticoenterostomy (PE) which can effectively reduce the incidence of CR-POPF and its potential neopathy is needed. We aimed to assess the efficacy of our modified duct-to-mucosa PE in the PD. METHOD: From January 2011 to December 2017, 233 consecutive patients with PD were retrospectively included from Shenzhen People's Hospital. After propensity score matching (PSM), there were 82 patients in both the modified duct-to-mucosa PE group (group A) and the conventional end-to-side inserting PE group (group B), respectively. The clinical course and the incidence of postoperative neopathy were compared between groups. Logistic regression method was utilized to analyze the association between PE approach and CR-POPF. RESULTS: The PE time was shorter in group A (9.3 ± 1.8 min vs. 21.5 ± 2.8 min, P < 0.001). The group A had significantly lower incidence of severe neopathy (Clavien-Dindo grade > II) [7.3% (5/82) vs. 17.1% (14/82), P = 0.028] and incidence of CR-POPF [1.2% (1/82) vs. 19.5% (12/82), P < 0.001] than the group B. Our modified duct-to-mucosa PE technique was associated with a reduced risk for CR-POPF (OR, 0.11 [95% CI, 0.02-0.57]; P = 0.009) as compared with the conventional end-to-side inserting PE. CONCLUSION: Compared with conventional end-to-side inserting PE, our modified duct-to-mucosa PE technique can effectively reduce the incidences of postoperative neopathy and CR-POPF. TRIAL REGISTRATION: Researchregistry3877 . Registered 24 March 2018. Retrospectively registered.

UBE2T promotes hepatocellular carcinoma cell growth via ubiquitination of p53.

Deregulation of Ubiquitin-conjugating enzyme E2T (UBE2T) contributes to the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unclear. Here, we show that UBE2T is up-regulated in HCC and exerts oncogenic activities via ubiquitination of p53. High UBE2T expression was correlated with higher pathological grade, advanced TNM stage, tumor vascular invasion, and poor overall and disease-free survivals in two independent cohorts containing 827 patients with HCC. UBE2T was further identified as an independent factor for overall survival by multivariate analyses. Luciferase reporter assays confirmed that UBE2T was directly targeted by miR-543 which was down-regulated in HCC. In vitro experiments demonstrated that UBE2T overexpression promoted, whereas UBE2T knockdown inhibited HCC cell growth. Ectopic expression of UBE2T resulted in the decreases of p53, p21 and Noxa. Further studies revealed that UBE2T facilitated the degradation of p53 protein via enhancing its ubiquitination. Collectively, our findings suggest UBE2T serves as a promising prognostic factor for HCC and functions as an oncogene. The newly identified miR-543/UBE2T/p53 axis may represent a new potential therapeutic target for HCC intervention.

Risk Models for Predicting the Recurrence and Survival in Patients With Hepatocellular Carcinoma Undergoing Radio-Frequency Ablation.

Background: Hepatocellular carcinoma (HCC) patients have a poor prognosis after radio-frequency ablation (RFA), and investigating the risk factors affecting RFA and establishing predictive models are important for improving the prognosis of HCC patients. Methods: Patients with HCC undergoing RFA in Shenzhen People's Hospital between January 2011 and December 2021 were included in this study. Using the screened independent influences on recurrence and survival, predictive models were constructed and validated, and the predictive models were then used to classify patients into different risk categories and assess the prognosis of different categories. Results: Cox regression model indicated that cirrhosis (hazard ratio [HR] = 1.65), alpha-fetoprotein (AFP) ⩾400 ng/mL (HR = 2.03), tumor number (multiple) (HR = 2.11), tumor diameter ⩾20 mm (HR = 2.30), and platelets (PLT) ⩾ 244 (109/L) (HR = 2.37) were independent influences for recurrence of patients after RFA. On the contrary, AFP ⩾400 ng/mL (HR = 2.48), tumor number (multiple) (HR = 2.52), tumor diameter ⩾20 mm (HR = 2.25), PLT ⩾244 (109/L) (HR = 2.36), and hemoglobin (HGB) ⩾120 (g/L) (HR = 0.34) were regarded as independent influences for survival. The concordance index (C-index) of the nomograms for predicting disease-free survival (DFS) and overall survival (OS) was 0.727 (95% confidence interval [CI] = 0.770-0.684) and 0.770 (95% CI = 0.821-7.190), respectively. The prognostic performance of the nomograms was significantly better than other staging systems by analysis of the time-dependent C-index and decision curves. Each patient was scored using nomograms and influencing factors, and patients were categorized into low-, intermediate-, and high-risk groups based on their scores. In the Kaplan-Meier survival curve, DFS and OS were significantly better in the low-risk group than in the intermediate- and high-risk groups. Conclusions: The 2 prediction models created in this work can effectively predict the recurrence and survival rates of HCC patients following RFA.

Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis.

OBJECTIVE: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC). METHODS: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study. RESULTS: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo. CONCLUSION: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

Calcyclin-binding protein contributes to cholangiocarcinoma progression by inhibiting ubiquitination of MCM2.

Background: Cholangiocarcinoma (CCA) represents the epithelial cell cancer with high aggressiveness whose five-year survival rate is poor with standard treatment. Calcyclin-binding protein (CACYBP) shows aberrant expression within several malignant tumors, but the role of CACYBP in CCA remains unknown. Methods: Immunohistochemical (IHC) analysis was used to identify CACYBP overexpression in clinical samples of CCA patients. Moreover, its correlation with clinical outcome was revealed. Furthermore, CACYBP's effect on CCA cell growth and invasion was investigated in vitro and in vivo using loss-of-function experiments. Results: CACYBP showed up-regulation in CCA, which predicts the dismal prognostic outcome. CACYBP had an important effect on in-vitro and in-vivo cancer cell proliferation and migration. Additionally, knockdown of CACYBP weakened protein stability by promoting ubiquitination of MCM2. Accordingly, MCM2 up-regulation partly reversed CACYBP deficiency's inhibition against cancer cell viability and invasion. Thus, MCM2 might drive CCA development by Wnt/ß-catenin pathway. Conclusions: CACYBP exerted a tumor-promoting role in CCA by suppressing ubiquitination of MCM2 and activating Wnt/ß-catenin pathway, hence revealing that it may be the possible therapeutic target for CCA treatment.

IHGA: An interactive web server for large-scale and comprehensive discovery of genes of interest in hepatocellular carcinoma.

Mining gene expression data is valuable for discovering novel biomarkers and therapeutic targets in hepatocellular carcinoma (HCC). Although emerging data mining tools are available for pan-cancer-related gene data analysis, few tools are dedicated to HCC. Moreover, tools specifically designed for HCC have restrictions such as small data scale and limited functionality. Therefore, we developed IHGA, a new interactive web server for discovering genes of interest in HCC on a large-scale and comprehensive basis. Integrative HCC Gene Analysis (IHGA) contains over 100 independent HCC patient-derived datasets (with over 10,000 tissue samples) and more than 90 cell models. IHGA allows users to conduct a series of large-scale and comprehensive analyses and data visualizations based on gene mRNA levels, including expression comparison, correlation analysis, clinical characteristics analysis, survival analysis, immune system interaction analysis, and drug sensitivity analysis. This method notably enhanced the richness of clinical data in IHGA. Additionally, IHGA integrates artificial intelligence (AI)-assisted gene screening based on natural language models. IHGA is free, user-friendly, and can effectively reduce time spent during data collection, organization, and analysis. In conclusion, IHGA is competitive in terms of data scale, data diversity, and functionality. It effectively alleviates the obstacles caused by HCC heterogeneity to data mining work and helps advance research on the molecular mechanisms of HCC.

Role of the pre- to postoperative alpha-fetoprotein ratio in the prognostic evaluation of liver cancer after radiofrequency ablation.

OBJECTIVE: This study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after radiofrequency ablation (RFA) in the prognosis of patients with liver cancer. METHODS: A total of 368 patients who underwent RFA for liver cancer in Shenzhen People's Hospital from 2010 to 2020 were randomly divided into the training group and the validation group. Levels of AFP before and after RFA were recorded and their ratios were calculated. RESULTS: Using the X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training group was 37.9. Both in the training group and the validation group, the relapse-free survival and overall survival of patients with an AFP ratio <37.9 (high-risk group) were significantly shorter than those with an AFP ratio >37.9 (low-risk group) (training group, relapse-free survival, P = 0.0003; overall survival, P = 0.0186; validation group, relapse-free survival, P = 0.0490, overall survival, P = 0.0031). An AFP ratio <37.9 was an independent risk factor for recurrence and survival of liver cancer after RFA. CONCLUSION: The AFP ratio can predict the prognosis of patients with liver cancer after RFA. An AFP ratio <37.9 is an independent risk factor for tumor recurrence and survival after RFA.

Acute abdominal disease associated with gallbladder torsion recovered after cholecystectomy: a rare case report and literature review.

Background: Gallbladder torsion is very rare and easily misdiagnosed as biliary disease. It is defined as the rotation of the gallbladder along the axis of the cystic pedicle on the mesentery. As gallbladder rotation involves the gallbladder artery, the blood supply is blocked, resulting in gallbladder ischemia and eventual necrosis. If misdiagnosis occurs and treatment is delayed, gallbladder torsion can develop into a lethal disease. The typical imaging features of gallbladder torsion in this case are a good learning resource for our young physicians, as well as providing a rare, unusual and typical case for our current literature database. Case Description: We present a rare case of gallbladder torsion in a 19-year-old man. The patient complained of sudden recurrent pain and discomfort in the right upper abdomen with vomiting for 12 hours. Abdominal ultrasound and computed tomography (CT) scan showed gallbladder enlargement and signs of acute cholecystitis in emergency examination, and there were no signs of cholecystolithiasis. Considering that the patient was a young male and the patients prefer conservative treatment, symptomatic treatment was given. However, there was no obvious effect after 1 day of medical treatment, but severe abdominal pain in the upper right quadrant continues to progress. Finally, the patient underwent laparoscopic cholecystectomy, and the gallbladder was found to be enlarged with ischemic necrosis, which was caused by gallbladder torsion. The patient recovered 2 days after surgery and was discharged without complications. Conclusions: Although the clinical manifestation is similar to that of typical acute calculous cholecystitis, gallbladder torsion can be diagnosed early through some special signs on imaging examination, such as distorted cystic duct signs ("beak and whirl" sign), gallbladder dilatation with gallbladder fossa effusion, and gallbladder in the horizontal position. These signs can help primary surgical treatment and prevent fatal complications such as gallbladder gangrene, perforation, and biliary peritonitis. Therefore, for inexperienced doctors, careful imaging features are required for the correct diagnosis of rare gallbladder torsion. Keywords: Gallbladder torsion; acute abdominal disease; cholecystitis; case report.

Diagnostic accuracy of 3D imaging combined with intra-operative ultrasound in the prediction of post-hepatectomy liver failure.

Background: The risk of post-hepatectomy liver failure (PHLF) is difficult to predict preoperatively. Accurate preoperative assessment of residual liver volume is critical in PHLF. Three-dimensional (3D) imaging and intra-operative ultrasound (IOUS) offer significant advantages in calculating liver volume and have been widely used in hepatectomy risk assessment. Our research aimed to explore the accuracy of 3D imaging technique combining IOUS in predicting PHLF after hepatectomy. Methods: We used a retrospective study design to analyze patients who underwent hepatectomy with 3D imaging combined with IOUS between 2017 and 2020. Utilizing 3D reconstruction, the patient's residual liver volumes (PRLVs) and ratio of PRLV to standard liver volume (SLV) were calculated preoperatively. Hepatectomy were performed and actual hepatectomy volume (AHV) were measured. Consistency between preoperative planned hepatectomy volume (PPHV) and AHV was quantified postoperatively by Bland-Altman analysis. Multiple logistic regression and receiver-operating characteristic (ROC) curves were utilized to discuss the predictive value of PRLV/SLV in PHLF. Results: Among the 214 included patients, 58 (27.1%) had PHLF. Patients with PHLF had significantly higher residual rates of ICG-R15 (%) (P=0.000) and a lower PRLV/SLV ratio (P=0.000). Bland-Altman analysis showed that PPHV was consistent with AHV (P=0.301). Multivariate analysis confirmed that PRLV/SLV ratio >60% (OR, 0.178; 95% CI: 0.084-0.378; P<0.01) was a protective factor for PHLF. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.8% (95% CI: 64.5.3-87.2%), 66.6% (95% CI: 59.1-74.1%), 45.8%, and 88.1%, respectively. The area under the ROC curve (AUC) was 73.7% (95% CI: 65.7-85.8%) and the diagnostic accuracy of PRLV/SLV for PHLF was moderate (P<0.001). These results were validated in the validation cohort perfectly. The primary cohort included 214 patients with a PHLF rate of 27.1% (n=58, 28 grade B and 13 grade C). The validation cohort included 135 patients with a PHLF rate of 35.6% (n=48, 24 grade B and 11 grade C). Conclusions: The calculation of PRLV/SLV has predictive value in PHLF and can be exploited as a predictive factor. The 3D imaging technique combined with IOUS may be useful for PHLF risk assessment in hepatectomy patients.

Ensemble learning based on efficient features combination can predict the outcome of recurrence-free survival in patients with hepatocellular carcinoma within three years after surgery.

Preoperative prediction of recurrence outcome in hepatocellular carcinoma (HCC) facilitates physicians' clinical decision-making. Preoperative imaging and related clinical baseline data of patients are valuable for evaluating prognosis. With the widespread application of machine learning techniques, the present study proposed the ensemble learning method based on efficient feature representations to predict recurrence outcomes within three years after surgery. Radiomics features during arterial phase (AP) and clinical data were selected for training the ensemble models. In order to improve the efficiency of the process, the lesion area was automatically segmented by 3D U-Net. It was found that the mIoU of the segmentation model was 0.8874, and the Light Gradient Boosting Machine (LightGBM) was the most superior, with an average accuracy of 0.7600, a recall of 0.7673, a F1 score of 0.7553, and an AUC of 0.8338 when inputting radiomics features during AP and clinical baseline indicators. Studies have shown that the proposed strategy can relatively accurately predict the recurrence outcome within three years, which is helpful for physicians to evaluate individual patients before surgery.

Outcomes of reoperation for hepatolithiasis with 3D imaging individualized preoperative planning technique: a single-center experience.

BACKGROUND: A detailed assessment of biliary tract anatomy is necessary for the successful reoperation for hepatolithiasis. This study aimed to evaluate the feasibility of preoperative individualized surgical planning with three-dimensional (3D) imaging technique for reoperation of hepatolithiasis. METHODS: This was a retrospective matched case-control study. From January 2011 to December 2018, 56 patients receiving reoperation according to the individualized preoperative plan based on 3D imaging at our center were included (group A). Meanwhile, 54 patients receiving traditional imaging guided reoperation matched by age, gender and distribution of hepatobiliary stones to each case were selected as controls (group B). The perioperative and long-term follow-up outcomes were compared between the two groups. RESULTS: There was no significant difference in demographic characteristics between groups. Compared with group B, the group A had a significantly shorter operation time (245.7±56.2 min vs. 305.2±79.9 min, P<0.001), a significantly higher surgical plan implementation rate (SPIR, 92.9% vs. 66.7%, P=0.001) and a lower incidence-of severe complications (Clavien-Dindo grade>II, 1.8% vs. 14.8%, P=0.015). The incidences of initial residual stone (7.1% vs. 44.4%, P<0.001) and repeated cholangitis (3.6% vs. 33.3%, P<0.001) were significantly lower in group A than in group B. After postoperative choledochoscopic lithotripsy, the incidence of final residual stones was significantly lower in group A than in group B. (1.8% vs. 20.4%, P=0.002). CONCLUSIONS: The preoperative 3D imaging assisted surgical planning is feasible and safe for reoperation of hepatolithiasis which can effectively improve surgical plan implementation rate and reduce the incidence of postoperative complications as compared with conventional surgical planning.

Role of long intergenic non-protein coding RNA 01857 in hepatocellular carcinoma malignancy via the regulation of the microRNA-197-3p/anterior GRadient 2 axis.

OBJECTIVE: This study investigates the differential expression and the mechanism of long intergenic non-protein coding RNA (LINC) 01857 in hepatocellular carcinoma (HCC) proliferation and apoptosis. METHODS: LINC01857 expression in HCC tissues and cells was evaluated. In addition, gain-of and loss-of functions were carried out to assess HCC cell proliferation and apoptosis. After that, LINC01857 subcellular localization was predicted and verified. Additionally, the binding relations between LINC01857 and microRNA (miRNA)-197-3p and between miR-197-3p and anterior GRadient 2 (AGR2) were detected and confirmed. Besides, HCC cell proliferation and apoptosis were assessed after silencing LINC01857 or overexpressing AGR2. Next, levels of key factors in the AKT and ERK pathways were measured. Additionally, xenograft transplantation was also conducted to confirm the effect of LINC01857 in HCC. RESULTS: LINC01857 was overexpressed in HCC. Silencing LINC01857 leads to a blockage in HCC cell proliferation but improved apoptosis. LINC01857 could competitively bind to miR-197-3p and thus upregulate AGR2. miR-197-3p was poorly expressed in HCC, while AGR2 was overexpressed. Mechanistically, downregulated miR-197-3p or overexpressed AGR2 were observed to attenuate the effect of the LINC01857 knockdown on suppressing cell proliferation and enhancing apoptosis. Moreover, LINC01857 activated the AKT and ERK pathways through the manipulation of the miR-197-3p/AGR2 axis in HCC. CONCLUSION: The results of this study indicated that LINC01857 was highly expressed in HCC, and it could improve HCC cell proliferation and reduce apoptosis via competitively binding to miR-197-3p, promoting AGR2 and upregulating the AKT and ERK pathways.

The E2F1/USP11 positive feedback loop promotes hepatocellular carcinoma metastasis and inhibits autophagy by activating ERK/mTOR pathway.

Deubiquitinase ubiquitin-specific protease 11 (USP11), a member of the deubiquitinating family, plays an important but still controversial role in cancer development. Namely, USP11 has been shown to promote the proliferation and metastasis of hepatocellular carcinoma (HCC), but the underlying molecular basis is poorly understood. This study aimed to unravel novel functions of USP11 in HCC, especially those related to autophagy. Here, EdU, migration and colony formation assays, and mouse models showed that USP11 played a crucial role in HCC cell proliferation and metastasis in vitro and in vivo. Results from co-immunoprecipitation and ubiquitination assays demonstrated that USP11 interacted with E2F1 and maintained E2F1 protein stability by removing its ubiquitin. Notably, E2F1 regulated USP11 expression at the transcriptional level. Thus, the E2F1/USP11 formed a positive feedback loop to promote the proliferation and migration of HCC cells. Moreover, E2F1/USP11 inhibited autophagy by regulating ERK/mTOR pathway. In addition, the combination treatment inhibition of USP11 and autophagy enhanced the apoptosis of HCC cells and inhibited the tumor growth in mice more effective than either treatment alone. Taken together, these results indicate that the E2F1/USP11 signal axis promotes HCC proliferation and metastasis and inhibits autophagy, which provides an experimental basis for the treatment of HCC.

Graphdiyne nanosheets as a platform for accurate copper(ii) ion detection via click chemistry and fluorescence resonance energy transfer.

A novel sensing platform for sensitive detection of copper(ii) ions (Cu2+) in living cells and body fluids was developed by taking advantage of the excellent fluorescence quenching ability of graphdiyne (GDY) and the high specificity of click chemistry for the first time.

A Regioselectively Oxidized 2D Bi/BiOx Lateral Nano-Heterostructure for Hypoxic Photodynamic Therapy.

Optoelectronic science and 2D nanomaterial technologies are currently at the forefront of multidisciplinary research and have numerous applications in electronics and photonics. The unique energy and optically induced interfacial electron transfer in these nanomaterials, enabled by their relative band alignment characteristics, can provide important therapeutic modalities for healthcare. Given that nano-heterostructures can facilitate photoinduced electron-hole separation and enhance generation of reactive oxygen species (ROS), 2D nano-heterostructure-based photosensitizers can provide a major advancement in photodynamic therapy (PDT), to overcome the current limitations in hypoxic tumor microenvironments. Herein, a bismuthene/bismuth oxide (Bi/BiOx)-based lateral nano-heterostructure synthesized using a regioselective oxidation process is introduced, which, upon irradiation at 660 nm, effectively generates 1 O2 under normoxia but produces cytotoxic •OH and H2 under hypoxia, which synergistically enhances PDT. Furthermore, this Bi/BiOx nano-heterostructure is biocompatible and biodegradable, and, with the surface molecular engineering used here, it improves tumor tissue penetration and increases cellular uptake during in vitro and in vivo experiments, yielding excellent oxygen-independent tumor ablation with 660 nm irradiation, when compared with traditional PDT agents.

In Vivo Enrichment and Elimination of Circulating Tumor Cells by Using a Black Phosphorus and Antibody Functionalized Intravenous Catheter.

The circulating tumor cell (CTC) count is closely related to cancer recurrence and metastasis. The technology that can in vivo destroy CTCs may bring great benefits to patients, which is an urgent clinical demand. Here, a minimally invasive therapeutic intravenous catheter for in vivo enriching and photothermal killing of CTCs is developed. The surface of catheter is modified with anti-EpCAM antibody and the interior is filled with black phosphorus nanosheets (BPNSs). CTCs in the peripheral blood are captured by the catheter continually with the aid of circulation. The captured CTCs are used for downstream analyses or in vivo eliminated by the near-infrared (NIR) photothermal effect of BPNSs. A capture efficiency of 2.1% is obtained during the 5 min of treatment, and 100% of the captured CTCs are killed by following NIR light irradiation in both an in vitro closed-loop circulation system and an in vivo rabbit model. This cost-effective modality for lowering the CTCs burden can be a good supplement to traditional therapies, which holds great promise as an effective clinical intervention for cancer patients.

Immunogenic exosome-encapsulated black phosphorus nanoparticles as an effective anticancer photo-nanovaccine.

Tumor vaccines are a promising form of cancer immunotherapy, but difficulties such as neo-antigen identification, activation of immune cells, and tumor infiltration prevent their clinical breakthrough. Interestingly, nanotechnology-based photothermal therapy (PTT) has great potential to overcome these barriers. Previous studies have shown that serum exosomes (hEX) from hyperthermia-treated tumor-bearing mice displayed an array of patient-specific tumor-associated antigens (TAAs), and strong immunoregulatory abilities in promoting dendritic cell (DC) differentiation and maturation. Here, we developed a tumor vaccine (hEX@BP) by encapsulating black phosphorus quantum dots (BPQDs) with exosomes (hEX) against a murine subcutaneous lung cancer model. In comparison with BPQDs alone (BP), hEX@BP demonstrated better long-term PTT performance, greater elevation of tumor temperature and tumor targeting efficacy in vivo. Vaccination with hEX@BP in combination with PTT further demonstrated an outstanding therapeutic efficacy against established lung cancer, and promoted the infiltration of T lymphocytes into the tumor tissue. Our findings demonstrated that hEX@BP might be an innovative cancer photo-nanovaccine that offers effective immuno-PTT against cancers.

Role of procalcitonin as a predictor in difficult laparoscopic cholecystectomy for acute cholecystitis case: A retrospective study based on the TG18 criteria.

Difficult laparoscopic cholecystectomy (DLC) is difficult to precisely predict before operation. This observational cohort study aimed to evaluate the predictive value of procalcitonin (PCT) for DLC in patients with acute cholecystitis (AC). A total of 115 patients were included in the study from January 2017 to April 2018. Multiple logistic regression and receiver-operating characteristic (ROC) were performed to evaluate the predictive value of PCT levels in DLC. Patients with DLC had significantly higher Tokyo Guidelines 2018 (TG18) grade (P = 0.002) and levels of C-reactive protein (CRP) (P = 0.007) and PCT (P < 0.001). The cut-off value of PCT for predicting DLC was 1.50 ng/ml. The sensitivity and specificity were 91.3% (95% CI 78.3-97.1) and 76.8% (95% CI 64.8-85.8), respectively. The area under ROC curve was 92.7% (95% CI 88.2-97.3, P < 0.001). Our results suggested that PCT was a good predictor for DLC in the AC patients, but further research is necessary. Monitoring of PCT trends in AC patients may be useful for preoperative risk assessment.

MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-ß/Smad pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality worldwide. Early growth response factor 1 (Egr1) plays a crucial role in cancer progression. However, its precise role in HCC has not been clear. Here, we identified the aggravating role of Egr1 in cell proliferation of HCC firstly. The expression of Egr1 was significantly increased in HCC tissues. Functionally, overexpression of Egr1 enhanced, whereas silenced Egr1 expression attenuated HCC cells proliferation in vitro. Mechanistically, up-regulated Egr1 induced cell proliferation through activating Transforming growth factor (TGF)-ß1/Smad signaling pathway concomitantly with upregulation of p-Smad2 and p-Smad3. Secondly, miR-181a-5p was down-regulated in clinical HCC specimens and its expression was inversely correlated with Egr1 expression. Functionally, overexpression of miR-181a-5p inhibited, whereas decreased expression of miR-181a-5p promoted HCC cells proliferation in vitro. Furthermore, we demonstrated that miR-181a-5p overexpression directly suppressed Egr1, resulting in a down-regulated TGF-ß1/Smad pathway. Besides, the silenced Egr1 expression could rescue the enhanced cell proliferation induced by miR-181a-5p inhibitor. Thus, we concluded that miR-181a-5p is a negative regulator of Egr1 that can suppress tumor proliferation in HCC through targeting Egr1/TGF-ß1/Smad pathway, which may be a potential therapeutic approach of HCC.