Synthesis of glucosamine-selenium compound and evaluation of its oral toxicity and in vitro anti-hepatitis B virus activity.

Selenium supplements are beneficial to human health, however, concerns regarding the toxicity of inorganic selenium have stimulated research on safer organic compounds. The main objective of this study was to develop a novel glucosamine-selenium compound (Se-GlcN), clarify its structure, and subsequently investigate its oral toxicity and in vitro anti-hepatitis B virus (HBV) activity. Electron microscopy, infrared, ultraviolet spectroscopy, nuclear magnetic resonance and thermogravimetric analyses revealed a unique binding mode of Se-GlcN, with the introduction of the Se-O bond at the C6 position, resulting in the formation of two carboxyl groups. In acute toxicity studies, the median lethal dose (LD50) of Se-GlcN in ICR mice was 92.31 mg/kg body weight (BW), with a 95 % confidence interval of 81.88-104.07 mg/kg BW. A 30-day subchronic toxicity study showed that 46.16 mg/kg BW Se-GlcN caused livers and kidneys damage in mice, whereas doses of 9.23 mg/kg BW and lower were safe for the livers and kidneys. In vitro studies, Se-GlcN at 1.25 µg/mL exhibited good anti-HBV activity, significantly reducing HBsAg, HBeAg, 3.5 kb HBV RNA and total HBV RNA by 45 %, 54 %, 84 %, 87 %, respectively. In conclusion, the Se-GlcN synthesized in this study provides potential possibilities and theoretical references for its use as an organic selenium supplement.

ETV2 regulating PHD2-HIF-1α axis controls metabolism reprogramming promotes vascularized bone regeneration.

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.

Interaction of Macrophages with Bone Healing Microenvironment: Mechanism and Biomaterials.

Extensive bone fractures, which can seriously impact both health and quality of life, cannot easily heal naturally, especially if the patient has an underlying medical condition or is aging. The most promising approach to addressing such fractures is bone regeneration through bone tissue engineering. Bone regeneration is a complex process that consists of three distinct phases: inflammation, repair, and remodeling. Macrophages play a bridging role between the various cells involved in each stage of bone regeneration, interacting with different microenvironments and advancing the bone healing process. Although the origin and function of macrophages have been extensively studied, the mechanisms underlying their interaction with the bone healing microenvironment remain unexplored, including the association of microenvironmental changes with macrophage reprogramming and the role of macrophages in cells in the microenvironment. This review summarizes the bone regeneration process and recent advances in research on interactions between macrophages and the bone healing microenvironment and discusses novel biological strategies to promote bone regeneration by modulating macrophages for the treatment of bone injury and loss.

Unleashing the dynamic and nonlinear relationship among new-type urbanization, foreign direct investment, and inclusive green growth in China: an environmental sustainability perspective.

As an important way for China to integrate into the international circulation, foreign direct investment (FDI) can not only increase China's capital accumulation but also directly affect inclusive green growth by promoting the diffusion and transfer of green technologies and activating the domestic market. Based on China's provincial panel data from 2007 to 2019, this paper discusses the following issues: first, Global Malmquist-Luenberger (GML) productivity index is used to measure and analyze the current situation of inclusive green growth in 30 provinces of China; second, we set a fixed effect panel model to test the relationship between FDI and inclusive green growth in China. Third, based on PVAR (panel vector autoregressive) model, the dynamic impacts of FDI and new urbanization on inclusive green growth are tested. Finally, a regression model with the new urbanization level as the threshold variable is constructed to test the threshold effect of FDI on China's green inclusive growth. Accordingly, each region needs to formulate FDI introduction policies according to the local new urbanization level, so as to give full play to the positive role of FDI in inclusive green growth.

The characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies: A systematic review.

BACKGROUND: The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies. METHODS: This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses. RESULTS: In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome. LIMITATIONS: The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.

The involvement of oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation in acrylamide-induced neurotoxicity in C57/BL6 mice.

Acrylamide (ACR) is a typical environmental contaminant, presenting potential health hazards that have been attracting increasing attention. Its neurotoxicity is known to cause significant damage to health. However, the mechanisms of ACR-induced neurotoxicity require further clarification. This study uses a mouse model to explore how ACR-induced oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation mutually contribute to neurotoxicity. A distinct increase in the cellular reactive oxygen species (ROS) levels, malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG) content and a significant decrease in the glutathione (GSH) content after ACR exposure were indicative of oxidative stress. Moreover, ACR caused neurological defects associated with gait abnormality and neuronal loss while suppressing the acetylcholine (ACh) and dopamine (DA) levels and increasing the protein expression of α-synuclein (α-syn), further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammatory response via nuclear factor-kappa B (NF-κB) activation and increased the protein expression of NOD-like receptor protein-3 (NLRP3), consequently activating the NLRP3 inflammasome constituents, including cysteinyl aspartate specific proteinase 1 (Caspase-1), apoptosis-associated speck-like protein containing CARD (ASC), N domain gasdermin D (N-GSDMD), interleukin-1ß (IL-1ß), and IL-18. The results revealed the underlying molecular mechanism of ACR-induced neurotoxicity via oxidative stress, neurotransmission impairment, and neuroinflammation-related signal cascade. This information will further improve the development of an alternative pathway strategy for investigating the risk posed by ACR. The hypothetical mechanism of ACR-induced neurotoxicity in vivo.

Comparison of chemotherapy regimens plus rituximab in adult Burkitt lymphoma: A single-arm meta-analysis.

Background and aim: Given the paucity of evidence-based treatment recommendations, the most appropriate first-line regimen for adult Burkitt lymphoma is currently undefined. We aimed to identify the optimal treatment regimen containing rituximab for adult Burkitt lymphoma patients. Methods: The PubMed, Embase, Web of Science, and Cochrane databases were searched in December 2021 (10). We included all studies for the treatment of Burkitt lymphoma including rituximab. We excluded studies of patients aged ≤14 years old and those with sample numbers ≤10 patients. Random-effects models were used to compare different chemotherapy regimens regarding estimated 2-year overall survival (OS) rate, 2-year progression-free survival (PFS) rate, and overall response rate (ORR). Results: A total of 17 studies were included in this meta-analysis and divided into four groups: CODOX-M/IVAC, DA-EPOCH, GMALL-B-ALL/NHL2002, and Hyper-CVAD. DA-EPOCH was associated with a significantly higher 2-year OS rate [0.95, 95% confidence interval (CI) 0.86-1.00]. There was no significant difference in the 2-year PFS rates (0.81, 95% CI 0.76-0.85) and ORR (0.90, 95% CI 0.87-0.94) between these four treatment regimens. Conclusions: The meta-analysis indicates that DA-EPOCH could be more effective in providing curative treatment for adult Burkitt lymphoma patients, especially without CNS and BM involvement considering OS time. Due to the types of studies and the limited number of included studies, bias should be acknowledged and a randomized controlled trial (RCT) needs to be performed to further identify the optimal treatment regimen for such patients.

Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling.

Periodontitis (PD) is a common chronic infectious disease. The local inflammatory response in the host may cause the destruction of supporting periodontal tissue. Macrophages play a variety of roles in PD, including regulatory and phagocytosis. Moreover, under the induction of different factors, macrophages polarize and form different functional phenotypes. Among them, M1-type macrophages with proinflammatory functions and M2-type macrophages with anti-inflammatory functions are the most representative, and both of them can regulate the tendency of the immune system to exert proinflammatory or anti-inflammatory functions. M1 and M2 macrophages are involved in the destructive and reparative stages of PD. Due to the complex microenvironment of PD, the dynamic development of PD, and various local mediators, increasing attention has been given to the study of macrophage polarization in PD. This review summarizes the role of macrophage polarization in the development of PD and its research progress.

Multifunctional Coatings of Titanium Implants Toward Promoting Osseointegration and Preventing Infection: Recent Developments.

Titanium and its alloys are dominant material for orthopedic/dental implants due to their stable chemical properties and good biocompatibility. However, aseptic loosening and peri-implant infection remain problems that may lead to implant removal eventually. The ideal orthopedic implant should possess both osteogenic and antibacterial properties and do proper assistance to in situ inflammatory cells for anti-microbe and tissue repair. Recent advances in surface modification have provided various strategies to procure the harmonious relationship between implant and its microenvironment. In this review, we provide an overview of the latest strategies to endow titanium implants with bio-function and anti-infection properties. We state the methods they use to preparing these efficient surfaces and offer further insight into the interaction between these devices and the local biological environment. Finally, we discuss the unmet needs and current challenges in the development of ideal materials for bone implantation.

Case report: Rare myeloid sarcoma development following renal transplantation with KRAS and DNMT3A gene mutations.

BACKGROUND: A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence. CASE PRESENTATION: Here, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation. CONCLUSIONS: Our report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.

Poly-l-lysine/Sodium Alginate Coating Loading Nanosilver for Improving the Antibacterial Effect and Inducing Mineralization of Dental Implants.

In recent years, antibacterial surface modification of titanium (Ti) implants has been widely studied in preventing implant-associated infection for dental and orthopedic applications. The purpose of this study was to prepare a composite coating on a porous titanium surface for infection prevention and inducing mineralization, which was initialized by deposition of a poly-l-lysine (PLL)/sodium alginate(SA)/PLL self-assembled coating, followed by dopamine deposition, and finally in situ reduction of silver nanoparticles (AgNPs) by dopamine. The surface zeta potential, SEM, XPS, UV-vis, and water contact angle analyses demonstrate that each coating was successfully prepared after the respective steps and that the average sizes of AgNPs were 20-30 nm. The composite coating maintained Ag+ release for more than 27 days in PBS and induced mineralization when incubated in SBF. The antibacterial results showed that the composite coating inhibited/killed bacteria on the material surface and killed bacteria around them. In addition, although this coating inhibited the initial adhesion of osteoblasts, the mineralized surface greatly enhanced the cytocompatibility. Thus, we concluded that the composite coating could prevent bacterial infections and facilitate mineralization in vivo in the early postoperative period, and then, the mineralized surface could enhance the cytocompatibility.

A Temporal Adaptive Access Mechanism for Data Fusion in an IoT Environment.

Data fusion in the Internet of Things (IoT) environment demands collecting and processing a wide variety of data with mixed time characteristics, both real-time and non-real-time data. Most of the previous research on data fusion was about the data processing aspect; however, successful data transmission is a prerequisite for high-performance data fusion in IoT. On the other hand, research on data transmissions in IoT mainly focuses on networking without sufficiently considering the special requirements of the upper-layer applications, such as the data fusion process, that are consuming the transmitted data. In this paper, we tackle the problem of data transmission for data fusion in an IoT environment by proposing a distributed scheduling mechanism VD-CSMA in wireless sensor networks, which considers the values for data fusion, as well as the delay constraints of packets when determining their priority levels for transmission. Simulation results have shown that VD-CSMA may enhance both throughput and delay performance of data transmission as compared to the typical scheduling schemes used for data fusion in IoT.

[Water Chemistry and Characteristics of Dissolved Organic Carbon During the Wet Season in Wulixia Reservoir, SW China].

In recent years, scientists have focused on the karst carbon cycle. To better understand the hydrochemical characteristics and the physical-chemical properties of DOC in the wet season in karst areas, the water chemistry and DOC distribution characteristics in Wulixia reservoir were analyzed. The molecular weight of the water organic matter was analyzed based on the UV absorption spectrum. The results showed that the water chemistry of Wulixia reservoir was HCO3-Ca ·Mg, the nutrient status of the water body was of the medium nutrient type, and the water maintained a good quality. The DOC mass concentration was lower in the wet season than in the dry season, and DOC was the main component of TOC. The DOC mass concentration tended to decrease from the surface to the bottom in a vertical direction. Chl-a and DIC were the main factors affecting the DOC vertical distribution. The organic matter in the reservoir area related to the absorption spectrum parameters of S275~295, M, SUVA254, and E253/E203 showed that the water was dominated by constituents with small molecular weight, a high proportion of fulvic acid, low proportion of humic acid, and weak aroma. The results showed that the organic matter in the reservoir area was readily consumed by microbial bioactivity and that it played an active role in the carbon cycle of the reservoir. It also showed that the DOC endogenous characteristics of the reservoir were strong and provided a sufficient carbon source for heterotrophic microbes.

[Carbon Metabolism Characteristics of the Karst Soil Microbial Community for Pb-Zn Mine Tailings].

BIOLOG and 18S rRNA PCR-DGGE methods were used to estimate the characteristics of carbon source metabolism of the soil microbial community as well as the relationship between soil fungi and soil organic carbon in different karst land use types (corn field, citrus field, and paddy field) contaminated by Pb-Zn tailings at Sidi Village, Yangshuo, Guangxi Zhuang Autonomous Region, SW China. It was found that the concentrations of Pb, Zn, Cu, and Cd were highest in the paddy field, followed by the corn field, citrus field, and control group (dry field). In addition, the geo-accumulation index indicated that the heavy metal pollution at this area was caused by Pb and Cd and that Cd was the key environmental risk factor. With the Pb-Zn tailings, there was low microbial biomass carbon, biological entropy, and microbial carbon source metabolism in the soil samples. The highest soil organic carbon and heavy metal concentrations were found in the paddy field, followed by the corn field and citrus field. According to the DDGE results, it was found that Pycnoporus sp. ZW02.30 was found in control group soils, Fusarium solani and Fusarium oxysporum were found in the corn field and citrus field, and Penicillium decumbens was found in citrus field. These were involved in the degradation of sugars, such as starch, cellulose, hemicellulose, and lignin. However, the fungi were not found in the paddy field. Based on the low functional diversity of the soil microbial community and biological entropy as well as the high soil organic carbon concentration in the paddy field, it was concluded that soil microbial carbohydrate metabolism and the mineralization rate of the soil organic carbon was controlled by soil microorganisms, especially fungi, in different land use soils in the karst area contaminated by Pb-Zn tailings.

Facile Soaking Strategy Toward Simultaneously Enhanced Conductivity and Toughness of Self-Healing Composite Hydrogels Through Constructing Multiple Noncovalent Interactions.

Tough and stretchable conductive hydrogels are desirable for the emerging field of wearable and implanted electronics. Unfortunately, most existing conductive hydrogels have low mechanical strength. Current strategies to enhance mechanical properties include employing tough host gel matrices or introducing specific interaction between conductive polymer and host gel matrices. However, these strategies often involve additional complicated processes. Here, a simple yet effective soaking treatment is employed to concurrently enhance mechanical and conductive properties, both of which can be facilely tailored by controlling the soaking duration. The significant improvements are correlated with co-occurring mechanism of deswelling and multiple noncovalent interactions. The resulting optimal sample exhibits attractive combination of high water content (75 wt %), high tensile stress (∼2.5 MPa), large elongation (>600%), reasonable conductivity (∼25 mS/cm), and fast self-healing property with the aid of hot water. The potential application of gel as a strain sensor is demonstrated. The applicability of this method is not limited to conductive hydrogels alone but can also be extended to strengthen other functional hydrogels with weak mechanical properties.

[Distinguishing the Properties and Sources of the Dissolved Organic Matter in Karst Reservoir Water During Winter Using Three-Dimensional Fluorescence Spectrum Technology:A Case Study in Wulixia Reservoir of Guangxi Province].

In recent years, the fluorescence spectrum technology has been widely applied to study the physical and chemical properties of dissolved organic matter (DOM) in natural water. In order to reveal the properties of the dissolved organic matter in reservoir water, the three-dimensional fluorescence spectrum and the parallel factor analysis were used to determine the properties of DOM and its sources in the Wulixia reservoir during the winter of 2016. Moreover, the chemical characteristics of water and the relative proportion of DOM fluorescent components were estimated. Results show that:① Ca2+ and HCO3- are the main cations and anions in the Wulixia reservoir during winter. The water is mainly controlled by the carbonate balance system and dissolved organic carbon (DOC) accounted for about 91% of total organic carbon (TOC). ③ DOM from the Wulixia reservoir can be divided into three components:fulvic acid, humic acid, and tryptophan. ③ The parameters, fluorescence index, humification index, biological index, and freshness index show the existence of DOM in the Wulixia reservoir. Microorganisms have a significant effect on DOM composition.

BlueDetect: An iBeacon-Enabled Scheme for Accurate and Energy-Efficient Indoor-Outdoor Detection and Seamless Location-Based Service.

The location and contextual status (indoor or outdoor) is fundamental and critical information for upper-layer applications, such as activity recognition and location-based services (LBS) for individuals. In addition, optimizations of building management systems (BMS), such as the pre-cooling or heating process of the air-conditioning system according to the human traffic entering or exiting a building, can utilize the information, as well. The emerging mobile devices, which are equipped with various sensors, become a feasible and flexible platform to perform indoor-outdoor (IO) detection. However, power-hungry sensors, such as GPS and WiFi, should be used with caution due to the constrained battery storage on mobile device. We propose BlueDetect: an accurate, fast response and energy-efficient scheme for IO detection and seamless LBS running on the mobile device based on the emerging low-power iBeacon technology. By leveraging the on-broad Bluetooth module and our proposed algorithms, BlueDetect provides a precise IO detection service that can turn on/off on-board power-hungry sensors smartly and automatically, optimize their performances and reduce the power consumption of mobile devices simultaneously. Moreover, seamless positioning and navigation services can be realized by it, especially in a semi-outdoor environment, which cannot be achieved by GPS or an indoor positioning system (IPS) easily. We prototype BlueDetect on Android mobile devices and evaluate its performance comprehensively. The experimental results have validated the superiority of BlueDetect in terms of IO detection accuracy, localization accuracy and energy consumption.

Robust Extreme Learning Machine With its Application to Indoor Positioning.

The increasing demands of location-based services have spurred the rapid development of indoor positioning system and indoor localization system interchangeably (IPSs). However, the performance of IPSs suffers from noisy measurements. In this paper, two kinds of robust extreme learning machines (RELMs), corresponding to the close-to-mean constraint, and the small-residual constraint, have been proposed to address the issue of noisy measurements in IPSs. Based on whether the feature mapping in extreme learning machine is explicit, we respectively provide random-hidden-nodes and kernelized formulations of RELMs by second order cone programming. Furthermore, the computation of the covariance in feature space is discussed. Simulations and real-world indoor localization experiments are extensively carried out and the results demonstrate that the proposed algorithms can not only improve the accuracy and repeatability, but also reduce the deviation and worst case error of IPSs compared with other baseline algorithms.

A fast and precise indoor localization algorithm based on an online sequential extreme learning machine.

Nowadays, developing indoor positioning systems (IPSs) has become an attractive research topic due to the increasing demands on location-based service (LBS) in indoor environments. WiFi technology has been studied and explored to provide indoor positioning service for years in view of the wide deployment and availability of existing WiFi infrastructures in indoor environments. A large body of WiFi-based IPSs adopt fingerprinting approaches for localization. However, these IPSs suffer from two major problems: the intensive costs of manpower and time for offline site survey and the inflexibility to environmental dynamics. In this paper, we propose an indoor localization algorithm based on an online sequential extreme learning machine (OS-ELM) to address the above problems accordingly. The fast learning speed of OS-ELM can reduce the time and manpower costs for the offline site survey. Meanwhile, its online sequential learning ability enables the proposed localization algorithm to adapt in a timely manner to environmental dynamics. Experiments under specific environmental changes, such as variations of occupancy distribution and events of opening or closing of doors, are conducted to evaluate the performance of OS-ELM. The simulation and experimental results show that the proposed localization algorithm can provide higher localization accuracy than traditional approaches, due to its fast adaptation to various environmental dynamics.

Herpes simplex virus thymidine kinase and ganciclovir suicide gene therapy for human pancreatic cancer.

AIM: To investigate the in vitro effects of suicide gene therapy system of herpes simplex virus thymidine kinase gene (HSV-TK) in combination with the treatment of nucleotide analog-ganciclovir (GCV) on human pancreatic cancer, and to provide a novel clinical therapeutic method for human pancreatic cancer. METHODS: We used a replication defective recombinant retrovirus vector GINaTK (bearing HSV-TK gene) to make packaging cell PA317 produce progeny virions. We then transferred the HSV-TK gene to target cells SW1990 using these progeny virions, and treated these gene-modified tumor cells with GCV to study the sensitivity of the cells to GCV and their bystander effects by routine MTT-method. RESULTS: Packaging cell PA317/TK was successfully constructed, and we acquired SW1990/TK through virus progeny infection. These gene-modified pancreatic cancer cells were sensitive to the treatment of GCV compared with unmodified tumor cells (t=4.15, n=10, P<0.0025). We also observed a remarkable bystander effect by mixing two kinds of cells at different ratio. CONCLUSION: Our data demonstrate that HSV-TK/GCV suicide gene therapy system is effective for treating experimental human pancreatic cancer, which is largely resistant to the common therapies, so the suicide gene therapy system may be a potential treatment approach for pancreatic cancer.