Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

The fate and prospects of stem cell therapy in the treatment of hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of long-term neurological disability in neonates and adults. Despite emerging advances in supportive care, like the most effective approach, hypothermia, poor prognosis has still been present in current clinical treatment for HIE. Stem cell therapy has been adopted for treating cerebral ischemia in preclinical and clinical trials, displaying its promising therapeutic value. At present, reported treatments for stroke employed stem cells to replace the lost neurons and integrate them into the existing host circuitry, promoting the release of growth factors to support and stimulate endogenous repair processes and so on. In this review, a meaningful overview to numerous studies published up to now was presented by introducing the preclinical and clinical research status of stem cell therapy for cerebral ischemia and hypoxia, discussing potential therapeutic mechanisms of stem cell transplantation for curing HI-induced brain injury, summarizing a series of approaches for marking transplanted cells and existing imaging systems for stem cell labelling and in vivo tracking and expounding the endogenous regeneration capability of stem cells in the newborn brain when subjected to an HI insult. Additionally, it is promising to combine stem therapy with neuromodulation through specific regulation of neural circuits. The crucial neural circuits across different brain areas related to functional recovery are of great significance for the application of neuromodulation strategies after the occurrence of neonatal hypoxic-ischemic encephalopathy (NHIE).

In Situ Construction of Bronze/Anatase TiO2 Homogeneous Heterojunctions and Their Photocatalytic Performances.

Photocatalytic degradation is one of the most promising emerging technologies for environmental pollution control. However, the preparation of efficient, low-cost photocatalysts still faces many challenges. TiO2 is a widely available and inexpensive photocatalyst material, but improving its catalytic degradation performance has posed a significant challenge due to its shortcomings, such as the easy recombination of its photogenerated electron-hole pairs and its difficulty in absorbing visible light. The construction of homogeneous heterojunctions is an effective means to enhance the photocatalytic performances of photocatalysts. In this study, a TiO2(B)/TiO2(A) homogeneous heterojunction composite photocatalyst (with B and A denoting bronze and anatase phases, respectively) was successfully constructed in situ. Although the construction of homogeneous heterojunctions did not improve the light absorption performance of the material, its photocatalytic degradation performance was substantially enhanced. This was due to the suppression of the recombination of photogenerated electron-hole pairs and the enhancement of the carrier mobility. The photocatalytic ability of the TiO2(B)/TiO2(A) homogeneous heterojunction composite photocatalyst was up to three times higher than that of raw TiO2 (pure anatase TiO2).

The anticancer mechanism investigation of Tanshinone IIA by pharmacological clustering in protein network.

BACKGROUND: Cancer is the second most common cause of death globally. The anticancer effects of Tanshinone IIA (Tan IIA) has been confirmed by numerous researches. However, the underlying mechanism remained to be integrated in systematic format. Systems biology embraced the complexity of cancer; therefore, a system study approach was proposed in the present study to explore the anticancer mechanism of Tan IIA based on network pharmacology. METHOD: Agilent Literature Search (ALS), a text-mining tool, was used to pull protein targets of Tan IIA. Then, pharmacological clustering was applied to classify obtained hits, the anticancer module was analysed further. The top ten essential nodes in the anticancer module were obtained by ClusterONE. Functional units in the anticancer module were catalogued and validated by Gene Ontology (GO) analysis. Meanwhile, KEGG and Cell Signalling Technology Pathway were employed to provide pathway data for potential anticancer pathways construction. Finally, the pathways were plotted using Cytoscape 3.5.1. Furthermore, in vitro experiments with five carcinoma cell lines were conducted. RESULTS: A total of 258 proteins regulated by Tan IIA were identified through ALS and were visualized by protein network. Pharmacological clustering further sorted 68 proteins that intimately involved in cancer pathogenesis based on Gene Ontology. Subsequently, pathways on anticancer effect of Tan IIA were delineated. Five functional units were clarified according to literature: including regulation on apoptosis, proliferation, sustained angiogenesis, autophagic cell death, and cell cycle. The GO analysis confirmed the classification was statistically significant. The inhibiting influence of Tan IIA on p70 S6K/mTOR pathway was revealed for the first time. The in vitro experiments displayed the selectivity of Tan IIA on HeLa, MDA-MB-231, HepG2, A549, and ACHN cell lines, the IC50 values were 0.54 µM, 4.63 µM, 1.42 µM, 17.30 µM and 204.00 µM, respectively. This result further reinforced the anticancer effect of Tan IIA treatment. CONCLUSIONS: The current study provides a systematic methodology for discovering the coordination of the anticancer pathways regulated by Tan IIA via protein network. And it also offers a valuable guidance for systematic study on the therapeutic values of other herbs and their active compounds.

Rubber-based carbon electrode materials derived from dumped tires for efficient sodium-ion storage.

The development of sustainable and low cost electrode materials for sodium-ion batteries has attracted considerable attention. In this work, a carbon composite material decorated with in situ generated ZnS nanoparticles has been prepared via a simple pyrolysis of the rubber powder from dumped tires. Upon being used as an anode material for sodium-ion batteries, the carbon composite shows a high reversible capacity and rate capability. A capacity as high as 267 mA h g-1 is still retained after 100 cycles at a current density of 50 mA g-1. The well dispersed ZnS nanoparticles in carbon significantly enhance the electrochemical performance. The carbon composites derived from the rubber powder are proposed as promising electrode materials for low-cost, large-scale energy storage devices. This work provides a new and effective method for the reuse of dumped tires, contributing to the recycling of valuable waste resources.

DanHong injection targets endothelin receptor type B and angiotensin II receptor type 1 in protection against cardiac hypertrophy.

Cardiac hypertrophy (CH) is an independent risk factor for cardiovascular diseases (CVDs). Mitigating or preventing CH is the most effective strategy for the treatment of CVDs. DanHong injection (DH) is a Chinese herbal medicine preparation (CHMP) widely used in clinical treatment of several CVDs in China. However, the direct targets and cellular mechanisms for these protective effects remain unclear. This study was designed to illustrate the direct targets of DH in protecting against CH and investigate CH molecular pathogenesis. A hypertrophic cell model was induced by endothelin-1 (ET-1) on human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). Real time cellular analysis (RTCA) cardio system and high content analysis (HCA) were used to detect the changes in contractile function, morphology and protein level of hypertrophic hiPS-CMs. Agonist and antagonist assay on receptors were performed using calcium mobilization high-throughput screening (HTS). DH significantly attenuated CH by modulating myocardial contractility, suppressing cell area enlargement and down-regulating ET-1-induced brain natriuretic peptide (BNP), actinin alpha 2 (ACTN2) and cardiac muscle troponin T (TNNT2) protein expression (P < 0.05). Endothelin receptor type B (ETBR) and angiotensin II receptor type 1 (AT1R) were DH direct targets, with IC50 value of 25.67 µL/mL and 1.10 µL/mL, respectively. Proteomics analysis showed that proteins involved in cell cycle inhibition, RNA processing, mitochondrial translation and cytoskeleton are significant regulated by DH treatment. These data revealed that ETBR and AT1R are DH direct targets on protecting against CH, providing a strategy to explore direct targets of CHMPs.

A metabolomic investigation into the effects of temperature on Streptococcus agalactiae from Nile tilapia (Oreochromis niloticus) based on UPLC-MS/MS.

Streptococcosis caused by Streptococcus agalactiae is one of the most serious diseases in farmed tilapia, and temperature is one of the most important environmental factors related to its outbreak. To elucidate the influence of temperature variation on the pathogen from a metabolic perspective, the global metabolomics of 2 pathogenic strains of S. agalactiae from sick tilapia were analyzed at 35°C and 25°C using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combined with pattern recognition approaches and pathway analysis. The result showed that the metabolic status of S. agalactiae was extensively affected by its culture temperature. Based on the results of metabolites contributing to these differences, a large number of nucleotides and their ramifications were markedly elevated at 35°C. Various energy substances, components of the cell wall and substances associated with stress regulation such as glyceraldehyde 3-phosphate, pyroglutamic acid, glutamate, d-Alanyl-d-alanine, glycerophosphocholine, dephospho-CoA, and oxidized glutathione increased when the strains were cultured at 35°C. Additionally, a general decrease in various precursors of capsule, antigen, and virulence protein formation were detected including mannose, maltotriose, N-acetyl-d-glucosamine 6-phosphate, uracil, proline, and citrulline. These metabolic changes indicated that metabolic activity decreased, while adaptive ability to environment and pathogenicity to host increased at high temperature. This study is the first to determine the metabolomic responses of S. agalactiae to temperature, and the results are useful to reveal its pathogenic mechanism and find effective disease control.

Reconstruction of polarization images from a multimode light-field imaging system.

The multimode light-field camera can capture spatial location and spectral and polarization characteristics of a target simultaneously. There is an aliasing effect, which causes the directly extracted image of a certain filter to include information from other filters. The reconstruction method proposed by Li (Jingzhen Li, thesis of Beihang University, 2015) can improve the accuracy of the polarization images, but the gray values still have gradient variations. In this paper, a method for reconstructing polarization images from the light-field image is proposed along with an aliasing model. Compared with the conventional direct-extraction and Li's methods, the proposed method can greatly reduce energy loss, and the accuracy of the reconstructed image increases more than fivefold.

Correlations of the expressions of c-Jun and Egr-1 proteins with clinicopathological features and prognosis of patients with nasopharyngeal carcinoma.

This study intended to explore the correlation of the expressions of c-Jun and Egr-1 proteins with clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2008 to January 2011, 123 NPC patients and 59 patients with chronic rhinitis were enrolled in this study. Fresh NPC and normal nasopharynx tissue specimens were obtained during surgery. Immunohistochemistry (IHC) was adopted to determine the positive expressions of the c-Jun and Egr-1 proteins. A 5-year clinical follow-up was conducted on all NPC patients. The Kaplan-Meier survival curve and Cox regression model were used for survival analysis. Compared with normal nasopharynx tissues, c-Jun expression was up-regulated but Egr-1 expression was down-regulated in NPC tissues. NPC patients with stage T3-T4 or stage III-IV had higher positive rates of c-Jun expression than those with stage T1-T2 or stage I-II. However, the positive rates of Egr-1 expression was higher in patients with stage T1-T2 or stage III-IV than those with stage T3-T4 or stage I-II. The survival rate of NPC patients with high c-Jun expression was lower than those with low/negative c-Jun expression, while the survival rate of NPC patients with high Egr-1 expression was higher than those with low/negative Egr-1 expression. The Cox regression analysis revealed that stage T3-T4, high c-Jun expression, and low Egr-1 expression were risk factors for poor prognosis of NPC patients. In conclusion, our study suggests that the c-Jun and Egr-1 proteins can serve as novel potential biomarkers for the early diagnosis and prognosis prediction of NPC.

Effects of thermal treatment on high solid anaerobic digestion of swine manure: Enhancement assessment and kinetic analysis.

Anaerobic digestion (AD), which is a process for generating biogas, can be applied to the treatment of organic wastes. Owing to its smaller footprint, lower energy consumption, and less digestate, high solid anaerobic digestion (HSAD) has attracted increasing attention. However, its biogas production is poor. In order to improve biogas production and decrease energy consumption, an improved thermal treatment process was proposed. Raw swine manure (>20% solid content) without any dilution was thermally treated at 70±1°C for different retention times, and then its effect on HSAD was investigated via batch AD experiments at 8.9% solid content. Results showed that the main organic components of swine manure hydrolyzed significantly during the thermal treatment, and HSAD's methane production rate was improved by up to 39.5%. Analysis using two kinetic models confirmed that the treatment could increase biodegradable organics (especially the readily biodegradable organics) in swine manure rather than upgrading its hydrolysis rate. It is worth noting that the superimposed first-order kinetics model was firstly applied in AD, and was a good tool to reveal the AD kinetics mechanism of substrates with complex components.

Effects of Liraglutide on Reperfusion Injury in Patients With ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Liraglutide, a glucagon-like peptide-1 analog, was reported to reduce reperfusion injury in mice. We planned to evaluate the effects of liraglutide on reperfusion injury in patients with acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. METHODS AND RESULTS: A total of 96 patients with ST-segment-elevation myocardial infarction undergoing emergency primary percutaneous coronary intervention were randomized to receive either subcutaneous liraglutide or placebo. Study treatment was commenced 30 minutes before intervention (1.8 mg) and maintained for 7 days after the procedure (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days). The salvage index was calculated from myocardial area at risk, measured during the index admission (35±12 hours), and final infarct size measured at 91±5 days after primary percutaneous coronary intervention by cardiac magnetic resonance. At 3 months, the primary end point, a higher salvage index was found in the liraglutide group than in the placebo group in 77 patients evaluated with cardiac magnetic resonance (0.66±0.14 versus 0.55±0.15; P=0.001). The final infarct size was lower in the liraglutide group than that in the placebo group (15±12 versus 21±15 g; P=0.05). Serum high-sensitivity C-reactive protein level was lower in the liraglutide group (P<0.001). During a 6-month follow-up period, no difference was observed in the incidence of major adverse cardiovascular event. Safety and tolerability were similar among the 2 groups. CONCLUSIONS: Our study provides evidence that liraglutide improves myocardial salvage and infarct size after ST-segment-elevation myocardial infarction, possibly by reducing reperfusion injury, making it a promising treatment for evaluation in larger trials. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02001363.

Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain.

BACKGROUND The aim of this study was to investigate the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone pain (CIBP). MATERIAL AND METHODS We established a rat CIBP model and a rat CIBP-morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13, neutralizing anti-CXCL13, and normal saline, while the control group rats underwent a sham operation and were injected with normal saline. The morphine analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) at various time points. The co-expressions of CXCL13 and NeuN were measured by immunofluorescence double-staining. CXCL13 protein and mRNA expressions were detected by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively. RESULTS Compared to the sham-operation (S) group, the BM group showed obviously decreased MWT and increased MWD on Day 9 after CIBP, but obviously increased MWT and decreased MWD on Day 3 after morphine administration; subsequently, the MWT was decreased and MWD was increased (all P<0.05). In comparison with the S+saline group, increased MWT and decreased MWD were observed in BM rats on Day 3 after anti-CXCL13 administration, and obviously decreased MWT and increased MWD were found in BM rats on Day 3 after rmCXCL13 administration (all P<0.05). CONCLUSIONS Up-regulated CXCL13 has a negative role in morphine analgesia in relief of CIBP, which may provide a new target for the management of CIBP.

[Pollution Source Identification of Water Body Based on Aqueous Fingerprint-Case Study].

Three-dimensional fluorescence spectroscopy is an emerging sensitive technology to detect organic pollution in water bodies. Based on this technique, a research group from Tsinghua University developed a novel instrument as a tool of pollution early-warning and pollution source identification，it has been put into use in A city in South China, for aqueous fingerprint monitoring and pollution sources identification under abnormal conditions. As a new monitoring method, it broke the limitation that traditional water quality monitoring technology could not provide directivity information of pollution source, and could detect abnormity of water quality quickly and identify pollution source accurately. In this paper, the process to identify pollution source during an abnormity incident of water quality in S River captured by the instrument was studied. When the instrument captured unidentified aqueous fingerprints during on-line monitoring, pollution intrusion process was inferred based on the variation of aqueous fingerprint figure and peak intensity. Then the pollution source identification was achieved by comparing the fingerprints between the polluted water body and possible pollution sources by the instrument. The source identification was verified with the changes of other water quality parameters such as pH, aniline, TOC and TN. The results showed that this early-warning and pollution source identification technique can quickly detect and release warning of abnormity of water quality and identify pollution sources accurately via monitoring aqueous fingerprints. The abnormity incident studied in this paper might be caused by dumping raw materials by a chemical plant located in upstream of the river.

[Fingerprint Properties of Semi Synthetic Penicillin Pharmaceutical Wastewater].

High-concentration antibiotics are detected in surface water from time to time. There has been an increasing demand for strengthening the supervision of the antibiotic pharmaceutical wastewater. Three-dimensional fluorescence technique is known as a rapid, simple and high-sensitivity method. The three-dimensional fluorescence spectrum can display organic components and it was named as aqueous fingerprint. In this paper, three-dimensional fluorescence characteristics of a typical semi synthetic penicillin pharmaceutical wastewater were studied. There were totally four fluorescence peaks in the aqueous fingerprint of this wastewater, locating in excitation wavelength/emission wavelength of 360/445, 255/445, 275/305 and 230/300 nm respectively. Fluorescence peak's intensity within certain range related linearly to the relative concentration. The possible fluorescent pollutants related to Peak C and Peak D might be the mixture of D-(-)-A-4-Hydroxyphenylglycine Dane Salt Methyl Potassium (pharmaceutical intermediates), Amoxicillin (pharmaceutical product) and D(-)-4-Hydroxyphenylglycine (pharmaceutical hydrolysate). PH played an important role in the fluorescence characteristics of this wastewater. This indicated that the fluorescent organic pollutants in this wastewater might contain acid or base groups. The aqueous fingerprint technique could be used to monitor the discharge of semi synthetic penicillin pharmaceutical wastewater as a novel tool.

[Impact of Thermal Treatment on Biogas Production by Anaerobic Digestion of High-solid-content Swine Manure].

Livestock manure is a kind of waste with high organic content and sanitation risk. In order to investigate the impact of thermal treatment on the anaerobic digestion of high-solid-content swine manure, 70 degrees C thermal treatment was conducted to treat raw manure (solid content 27.6%) without any dilution. The results indicated that thermal treatment could reduce the organic matters and improve the performance of anaerobic digestion. When the thermal treatment time was 1d, 2d, 3d, 4d, the VS removal rates were 15.1%, 15.5%, 17.8% and 20.0%, respectively. The methane production rates (CH4/VSadd) were 284.4, 296.3, 309.2 and 264.4 mL x g(-1), which was enhanced by 49.7%, 55.9%, 62.7% and 39.2%, respectively. The highest methane production rate occurred when the thermal treatment time was 3d. The thermal treatment had an efficient impact on promoting the performance of methane production rate with a suitable energy consumption. On the other hand, thermal treatment could act as pasteurization. This showed that thermal treatment would be of great practical importance.

[Aqueous Fingerprint of Printing and Dyeing Wastewater].

Aqueous fingerprint has an advantage to represent the organic components of water samples as compared to traditional parameters such as chemical oxygen demand (COD) and total organic carbon (TOC). Printing and dyeing wastewater is one of the major types of industrial wastewater in China. It is of huge volume and heavy pollution, containing large numbers of luminescent components and being difficult to be degraded. In this study the aqueous fingerprint of printing and dyeing wastewater was investigated with the fluorescent spectrometry. The experimental results showed that there existed two peaks in the aqueous fingerprint of the printing and dyeing wastewater, locating at the excitation/emission wavelength around 230/340 nm and 280/310 nm respectively. The intensity of the excitation/emission wavelength at 230/340 nm was higher than that of 280/310 nm. The locations and intensities of peaks varied within small range. The intensities of the two peaks linearly correlated with coefficient of 0.910 8 and slope of 1.506. The intensity ratio of Peak at 280/310 nm to Peak at 230/340 nm averagely was 0.777, ranging between 0.712 and 0.829. It was found that the aqueous fingerprints of sewage and aniline compounds were significantly different from that of the printing and dyeing wastewater, but the aqueous fingerprints of several types of widely-used dye were similar to that of the printing and dyeing wastewater. Thus dye may be the main luminescent components in the wastewater. The aqueous fingerprint can be used as a novel tool of early warning of waterbodies.