Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1.

Aminoglycoside antibiotics, including gentamicin (GM), induce delayed ototoxic effects such as hearing loss after prolonged use, which results from the death of hair cells. However, the mechanisms underlying the ototoxicity of aminoglycosides warrant further investigation, and there are currently no effective drugs in the clinical setting. Herein, the therapeutic effect of the flavonoid compound rutin against the ototoxic effects of GM in zebrafish hair cells was investigated. Animals incubated with rutin (100-400 µmol/L) were protected against the pernicious effects of GM (200 µmol/L). We found that rutin improves hearing behavior in zebrafish, and rutin was effective in reducing the number of Tunel-positive cells in the neuromasts of the zebrafish lateral line and promoting cell proliferation after exposure to GM. Subsequently, rutin exerted a protective effect against GM-induced cell death in HEI-OC1 cells and could limit the production of cytosolic reactive oxygen species (ROS) and diminish the percentage of apoptotic cells. Additionally, the results of the proteomic analysis revealed that rutin could effectively inhibit the expression of necroptosis and apoptosis related genes. Meanwhile, molecular docking analysis revealed a high linking activity between the molecular docking of rutin and STAT1 proteins. The protection of zebrafish hair cells or HEI-OC1 cells from GM-induced ototoxicity by rutin was attenuated by the introduction of STAT1 activator. Finally, we demonstrated that rutin significantly improves the bacteriostatic effect of GM by in vitro experiments, emphasising its clinical application value. In summary, these results collectively unravel a novel therapeutic role for rutin as an otoprotective drug against the adverse effects of GM.

Salivary proteins potentially derived from horizontal gene transfer are critical for salivary sheath formation and other feeding processes.

Herbivorous insects employ an array of salivary proteins to aid feeding. However, the mechanisms behind the recruitment and evolution of these genes to mediate plant-insect interactions remain poorly understood. Here, we report a potential horizontal gene transfer (HGT) event from bacteria to an ancestral bug of Eutrichophora. The acquired genes subsequently underwent duplications and evolved through co-option. We annotated them as horizontal-transferred, Eutrichophora-specific salivary protein (HESPs) according to their origin and function. In Riptortus pedestris (Coreoidea), all nine HESPs are secreted into plants during feeding. The RpHESP4 to RpHESP8 are recently duplicated and found to be indispensable for salivary sheath formation. Silencing of RpHESP4-8 increases the difficulty of R. pedestris in probing the soybean, and the treated insects display a decreased survivability. Although silencing the other RpHESPs does not affect the salivary sheath formation, negative effects are also observed. In Pyrrhocoris apterus (Pyrrhocoroidea), five out of six PaHESPs are secretory salivary proteins, with PaHESP3 being critical for insect survival. The PaHESP5, while important for insects, no longer functions as a salivary protein. Our results provide insight into the potential origin of insect saliva and shed light on the evolution of salivary proteins.

Co-option of a non-retroviral endogenous viral element in planthoppers.

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.

Horizontally Transferred Salivary Protein Promotes Insect Feeding by Suppressing Ferredoxin-Mediated Plant Defenses.

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.

Organic-Inorganic Hybrid Interfaces Enable the Preparation of Nitrogen-Doped Hollow Carbon Nanospheres as High-Performance Anodes for Lithium and Potassium-Ion Batteries.

An abundant hollow nanostructure is crucial for fast Li+ and K+ diffusion paths and sufficient electrolyte penetration, which creates a highly conductive network for ionic and electronic transport. In this study, we successfully developed a molecular-bridge-linked, organic-inorganic hybrid interface that enables the preparation of in situ nitrogen-doped hollow carbon nanospheres. Moreover, the prepared HCNSs, with high nitrogen content of up to 10.4%, feature homogeneous and regular morphologies. The resulting HCNSs exhibit excellent lithium and potassium storage properties when used as electrode materials. Specifically, the HCNS-800 electrode demonstrates a stable reversible discharge capacity of 642 mA h g-1 at 1000 mA g-1 after 500 cycles for LIBs. Similarly, the electrode maintains a discharge capacity of 205 mA h g-1 at 100 mA g-1 after 500 cycles for KIBs. Moreover, when coupled with a high-mass-loading LiFePO4 cathode to design full cells, the HCNS-800‖LiFePO4 cells provide a specific discharge capacity of 139 mA h g-1 at 0.1 C. These results indicate that the HCNS electrode has promising potential for use in high-energy and environmentally sustainable lithium-based and potassium-based batteries.

A clustering-optimized segmentation algorithm and application on food quality detection.

For solving the problem of quality detection in the production and processing of stuffed food, this paper suggests a small neighborhood clustering algorithm to segment the frozen dumpling image on the conveyor belt, which can effectively improve the qualified rate of food quality. This method builds feature vectors by obtaining the image's attribute parameters. The image is segmented by a distance function between categories using a small neighborhood clustering algorithm based on sample feature vectors to calculate the cluster centers. Moreover, this paper gives the selection of optimal segmentation points and sampling rate, calculates the optimal sampling rate, suggests a search method for optimal sampling rate, as well as a validity judgment function for segmentation. Optimized small neighborhood clustering (OSNC) algorithm uses the fast frozen dumpling image as a sample for continuous image target segmentation experiments. The experimental results show the accuracy of defect detection of OSNC algorithm is 95.9%. Compared with other existing segmentation algorithms, OSNC algorithm has stronger anti-interference ability, faster segmentation speed as well as more efficiently saves key information ability. It can effectively improve some disadvantages of other segmentation algorithms.

A reasonable identification of the early recurrence time based on microvascular invasion for hepatocellular carcinoma after R0 resection: A multicenter retrospective study.

BACKGROUND: Early and late recurrence of hepatocellular carcinoma (HCC) have different clinical outcomes, especially for those accompanied by microvascular invasion (MVI), but the definition of early recurrence remains controversial. Therefore, a reasonable identification of the early recurrence time for HCC is urgently needed. METHODS: Resected recurrence patients were enrolled and divided into two cohorts, one for identification of the early recurrence time and another for verification of the accuracy of the point. Univariable and multivariable Cox regression analyses were adopted to identify the prognostic factors of recurrence HCC (rHCC) and Kaplan-Meier method was applied to analyze the overall survival (OS). The appropriate cutoff value was determined by the exhaustive method using different recurrence intervals from 1 to 24 months in turn. RESULTS: In total, 292 resected rHCC patients were analyzed to calculate the early recurrence interval, and another 421 resected rHCC patients with MVI were enrolled to verify the efficacy of adjuvant transarterial chemoembolization (TACE) in this recurrence interval. MVI was identified as an independent risk factor by multivariable analysis. The OS of rHCC patients without MVI is better than that of patients with MVI when the recurrence time was within 13 months, while not beyond 13 months. The verification cohort demonstrated that adjuvant TACE provided longer survival for rHCC with MVI when the recurrence time was within 13 months, while not beyond 13 months. CONCLUSION: For HCC patients with MVI who underwent R0 resection, 13 months may be a reasonable early recurrence time point, and within this interval, postoperative adjuvant TACE may result in longer survival compared with surgery alone.

Planthopper salivary sheath protein LsSP1 contributes to manipulation of rice plant defenses.

Salivary elicitors secreted by herbivorous insects can be perceived by host plants to trigger plant immunity. However, how insects secrete other salivary components to subsequently attenuate the elicitor-induced plant immunity remains poorly understood. Here, we study the small brown planthopper, Laodelphax striatellus salivary sheath protein LsSP1. Using Y2H, BiFC and LUC assays, we show that LsSP1 is secreted into host plants and binds to salivary sheath via mucin-like protein (LsMLP). Rice plants pre-infested with dsLsSP1-treated L. striatellus are less attractive to L. striatellus nymphs than those pre-infected with dsGFP-treated controls. Transgenic rice plants with LsSP1 overexpression rescue the insect feeding defects caused by a deficiency of LsSP1 secretion, consistent with the potential role of LsSP1 in manipulating plant defenses. Our results illustrate the importance of salivary sheath proteins in mediating the interactions between plants and herbivorous insects.

Inhibition of ferroptosis by icariin treatment attenuates excessive ethanol consumption-induced atrial remodeling and susceptibility to atrial fibrillation, role of SIRT1.

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.

[Modified Kaixin San improves memory and synaptic damage of mice with Alzheimer's disease by modulating αCaMKâ ¡-PSD95 protein binding through inhibition of neuroinflammation:a study of mechanism].

To investigated the mechanisms underlying the effects of modified Kaixin San(MKXS) on improving memory and synaptic damage of Alzheimer's disease(AD) mouse model with conditional presenilin 1/2 conditional double knockout(PS cDKO). Specifically, 60 PS cDKO mice(3-3.5 months old) and their age-matched wild-type(WT) littermates were randomized into three groups: WT group(n=20), PS cDKO group(n=20), and PS cDKO+MKXS group(n=20). Mice in WT and PS cDKO groups were fed with standard chow and those in PS cDKO+MKXS group were given chow containing MKXS(at 2.55 g·kg~(-1)) for 60 days. Novel object reco-gnition task was employed to detect the recognition memory of mice, and Western blot to detect the protein levels of synapse-associated proteins in the hippocampus(HPC) of mice, such as NR1, NR2 A, NR2 B, p-αCaMKⅡ, tau, and p-tau. Microglial morphology in the HPC CA1 of mice was observed based on immunohistochemistry. Quantitative real time-PCR(qRT-PCR) was employed to detect the mRNA levels of the pro-inflammatory factors and synapse-associated proteins in the HPC of mice, including COX-2, iNOS, IL-1ß, IL-6, TNF-α, PSD95, NR1, NR2 A, NR2 B, and MAP2. The protein levels of IL-1ß, TNF-α, and IL-6 were tested by enzyme-linked immunosorbent assay(ELISA). The interaction between PSD95 and αCaMKⅡ and between PSD95 and p-αCaMKⅡ was tested by co-immunoprecipitation(Co-IP). The results showed that PS cDKO+MKXS demonstrated significantly higher preference index and recognition index of the new objects, lower protein level of p-tau(ser 396/404) and mRNA levels of COX-2, iNOS, TNF-α, IL-1ß, and IL-6 in HPC, higher protein levels of NR1, NR2 A, NR2 B, and p-αCaMKⅡ and mRNA levels of NR1, NR2 A, NR2 B, PSD95, and MAP2, and stronger interaction of αCaMKⅡ with PSD95 and interaction of p-αCaMKⅡ with PSD95 than the PS cDKO group. Immunohistoche-mical staining showed that MKXS inhibited the activation of microglia. In conclusion, MKXS improves memory and synaptic damage in mice with AD by modulating αCaMKⅡ-PSD95 protein binding through inhibition of neuroinflammation.

Efficacy and safety of transarterial chemoembolization plus antiangiogenic- targeted therapy and immune checkpoint inhibitors for unresectable hepatocellular carcinoma with portal vein tumor thrombus in the real world.

Purpose: This study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: Consecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: As of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period. Conclusions: TACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities.

Network Construction for Bearing Fault Diagnosis Based on Double Attention Mechanism.

Aiming at the difficulty of feature extraction in the case of multicomponent and strong noise in the traditional rolling bearing fault diagnosis method, this paper proposes a bearing fault diagnosis network with double attention mechanism. The original signal with noise is decomposed into a series of intrinsic mode functions (IMFs) by the Empirical Mode Decomposition method. The Pearson correlation coefficient is discussed to filter the IMFs components for signal reconstruction. The spatial features of the reconstructed signal are extracted by attention convolutional networks. Then, time series features are extracted based on the long short-term memory method. Furthermore, the importance of temporal features is measured through a temporal attention mechanism. The Softmax layer of the constructed network is used as the classifier for fault diagnosis. Comparing this method with the existing methods of experiments, the proposed method has not only better diagnosis accuracy but also stronger antiinterference ability and generalization ability, which can accurately diagnose and classify the bearing fault types. The fault diagnosis accuracy rate for each load is above 99%.

Icariin attenuates excessive alcohol consumption-induced susceptibility to atrial fibrillation through SIRT3 signaling.

Excessive alcohol consumption has long been identified as a risk factor for adverse atrial remodeling and atrial fibrillation (AF). Icariin is a principal active component from traditional Chinese medicine Herba Epimedii and has been demonstrated to exert potential antiarrhythmic effect. The present study was designed to evaluate the effect of icariin against alcohol-induced atrial remodeling and disruption of mitochondrial dynamics and furthermore, to elucidate the underlying mechanisms. Excessive alcohol-treated C57BL/6 J mice were infected with serotype 9 adeno-associated virus (AAV9) carrying mouse SIRT3 gene or negative control virus. Meanwhile, icariin (50 mg/kg/d) was administered to the animals in the presence or absence of AAV9 carrying SIRT3 shRNA. We noted that 8 weeks of icariin treatment effectively attenuated alcohol consumption-induced atrial structural and electrical remodeling as evidenced by reduced AF inducibility and reversed atrial electrical conduction pattern as well as atrial enlargement. Furthermore, icariin-treated group exhibited significantly enhanced atrial SIRT3-AMPK signaling, decreased atrial mitoSOX fluorescence and mitochondrial fission markers, elevated mitochondrial fusion markers (MFN1, MFN2) as well as NRF-1-Tfam-mediated mitochondrial biogenesis. Importantly, these beneficial effects were mimicked by SIRT3 overexpression while abolished by SIRT3 knockdown. These data revealed that targeting atrial SIRT3-AMPK signaling and preserving mitochondrial dynamics might serve as the novel therapeutic strategy against alcohol-induced AF genesis. Additionally, icariin ameliorated atrial remodeling and mitochondrial dysfunction by activating SIRT3-AMPK signaling, highlighting the use of icariin as a promising antiarrhythmic agent in this circumstance.

Polydatin attenuates chronic alcohol consumption-induced cardiomyopathy through a SIRT6-dependent mechanism.

Polydatin has attracted much attention as a potential cardioprotective agent against ischemic heart disease and diabetic cardiomyopathy. However, the effect and mechanism of polydatin supplementation on alcoholic cardiomyopathy (ACM) are still unknown. This study aimed to determine the therapeutic effect of polydatin against ACM and to explore the molecular mechanisms with a focus on SIRT6-AMP-activated protein kinase (AMPK) signaling and mitochondrial function. The ACM model was established by feeding C57/BL6 mice with an ethanol Lieber-DeCarli diet for 12 weeks. The mice received polydatin (20 mg kg-1) or vehicle treatment. We showed that polydatin treatment not only improved cardiac function but also reduced myocardial fibrosis and dynamin-related protein 1 (Drp-1)-mediated mitochondrial fission, and enhanced PTEN-induced putative kinase 1 (PINK1)-Parkin-dependent mitophagy in alcohol-treated myocardium. Importantly, these beneficial effects were mimicked by SIRT6 overexpression but abolished by the infection of recombinant serotype 9 adeno-associated virus (AAV9) carrying SIRT6-specific small hairpin RNA. Mechanistically, alcohol consumption induced a gradual decrease in the myocardial SIRT6 level, while polydatin effectively activated SIRT6-AMPK signaling and modulated mitochondrial dynamics and mitophagy, thus reducing oxidative stress damage and preserving mitochondrial function. In summary, these data present new information regarding the therapeutic actions of polydatin, suggesting that the activation of SIRT6 signaling may represent a new approach for tackling ACM-related cardiac dysfunction.

Perovskite-Gallium Nitride Tandem Light-Emitting Diodes with Improved Luminance and Color Tunability.

Tandem structures with different subpixels are promising for perovskite-based multicolor electroluminescence (EL) devices in ultra-high-resolution full-color displays; however, realizing excellent luminance- and color-independent tunability considering the low brightness and stability of blue perovskite light-emitting diodes (PeLEDs) remains a challenge. Herein, a bright and stable blue gallium nitride (GaN) LED is utilized for vertical integration with a green MAPbBr3 PeLED, successfully achieving a Pe-GaN tandem LED with independently tunable luminance and color. The electronic and photonic co-excitation (EPCE) effect is found to suppress the radiative recombination and current injection of PeLEDs, leading to degraded luminance and current efficiency under direct current modulation. Accordingly, the pulse-width modulation is introduced to the tandem device with a negligible EPCE effect, and the average hybrid current efficiency is significantly improved by 139.5%, finally achieving a record tunable luminance (average tuning range of 16631 cd m-2 at an arbitrary color from blue to green) for perovskite-based multi-color LEDs. The reported excellent independent tunability can be the starting point for perovskite-based multicolor EL devices, enabling the combination with matured semiconductor technologies to facilitate their commercialization in advanced display applications with ultra-high resolution.

Prognostic Comparison Between Liver Resection and Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Patients With Bile Duct Tumor Thrombus: A Propensity-Score Matching Analysis.

Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of this study is to evaluate the long-term prognosis of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) in these patients. Methods: Data from HCC patients with BDTT who underwent liver resection and TACE were analyzed respectively. Propensity score matching (PSM) analysis was performed in these patients. Results: A total of 145 HCC patients with BDTT were divided into two groups: the LR group (n = 105) and the TACE group (n = 40). The median OS in the LR group was 8.0 months longer than that in the TACE group before PSM (21.0 vs. 13.0 months, P <0.001) and 9.0 months longer after PSM (20.0 vs. 11.0 months, P <0.001). The median DFS in the LR group was 3.5 months longer than that in the TACE group before PSM (7.0 vs. 3.5 months, P = 0.007) and 5 months longer after PSM (7.0 vs. 2.0 months, P = 0.007). Conclusion: If surgery is technically feasible, liver resection provides better prognosis for HCC patients with BDTT compared with TACE.

Patterns, treatments, and prognosis of tumor recurrence after resection for hepatocellular carcinoma with microvascular invasion: a multicenter study from China.

BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.

Association of type 2 diabetes mellitus with incidences of microvascular invasion and survival outcomes in hepatitis B virus-related hepatocellular carcinoma after liver resection: A multicenter study.

BACKGROUND: Microvascular invasion (MVI) adversely affects long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aimed to examine the association between preoperative type 2 diabetes mellitus (T2DM) with incidences of MVI and prognosis in HBV-related HCC after liver resection (LR). MATERIAL AND METHODS: Data of HBV-related HCC patients who underwent LR as an initial therapy from four hospitals in China were retrospectively collected. Clinicopathological factors associated with the incidence of MVI were identified using univariate and multivariate logistic regression analysis. The recurrence-free survival (RFS) and overall survival (OS) curves between different cohorts of patients were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Of 1473 patients who were included, 219 (14.9%) patients had T2DM. Preoperative T2DM, HBV DNA load, antiviral treatment, AFP level, varices, and tumor encapsulation were identified to be independent predictors of the incidence of MVI. Patients with HBV-related HCC and T2DM had a higher incidence of MVI (65.8%) than those without T2DM (55.4%) (P = 0.004). The RFS and OS were significantly worse in patients with T2DM than those without T2DM (median RFS: 11.1 vs 16.7 months; OS: 26.4 vs 42.6 months, both P < 0.001). Equivalent results were obtained in HCC patients with MVI who had or did not have T2DM (median RFS: 10.0 vs 15.9 months; OS: 24.5 vs 37.9 months, both P < 0.001). CONCLUSIONS: Preoperative T2DM was an independent risk factor of incidence of MVI. Patients with HBV-related HCC and T2DM had worse prognosis than those without T2DM after LR.

Liver resection versus intensity-modulated radiation therapy for treatment of hepatocellular carcinoma with hepatic vein tumor thrombus: a propensity score matching analysis.

BACKGROUND: The presence of hepatic vein tumor thrombus (HVTT) is a major determinant of survival outcomes in hepatocellular carcinoma (HCC) patients. This study compared survival outcomes between liver resection (LR) and intensity-modulated radiation therapy (IMRT) in HCC patients with HVTT. METHODS: Data from patients who underwent LR or IMRT for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Their survival outcomes were compared before and after propensity score matching (PSM). RESULTS: Three hundred and seven HCC patients with HVTT who underwent either LR (n=140) or IMRT (n=167) were enrolled. PSM matched 82 pairs of patients. The overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher for patients in the LR group than those in the IMRT group. On subgroup analysis, significantly better survival outcomes were obtained after LR than IMRT in patients with peripheral type of HVTT (pHVTT) and major type of HVTT (mHVTT). However, similar survival outcomes were obtained after LR and IMRT when the HVTT had developed into inferior vena cava tumor thrombus (IVCTT). CONCLUSIONS: LR resulted in significantly better survival outcomes in HCC patients with HVTT when compared to IMRT. Once the HVTT had developed IVCTT, LR and IMRT resulted in similarly bad survival outcomes.