The C4 Protein of TbLCYnV Promotes SnRK1 ß2 Degradation Via the Autophagy Pathway to Enhance Viral Infection in N. benthamiana.

Geminiviruses are a group of single-stranded DNA viruses that have developed multiple strategies to overcome host defenses and establish viral infections. Sucrose nonfermenting-1-related kinase 1 (SnRK1) is a key regulator of energy balance in plants and plays an important role in plant development and immune defenses. As a heterotrimeric complex, SnRK1 is composed of a catalytic subunit α (SnRK1 α) and two regulatory subunits, ß and γ. Previous studies on SnRK1 in plant defenses against microbial pathogens have mainly focused on SnRK1 α. In this study, we validated the interaction between the C4 protein encoded by tobacco leaf curl Yunnan virus (TbLCYnV) and the regulatory subunit ß of Nicotiana benthamiana SnRK1, i.e., NbSnRK1 ß2, and identified that the Asp22 of C4 is critical for TbLCYnV C4-NbSnRK1 ß2 interactions. NbSnRK1 ß2 silencing in N. benthamiana enhances susceptibility to TbLCYnV infection. Plants infected with viral mutant TbLCYnV (C4D22A), which contains the mutant version C4 (D22A) that is incapable of interacting with NbSnRK1 ß2, display milder symptoms and lower viral accumulation. Furthermore, we discovered that C4 promotes NbSnRK1 ß2 degradation via the autophagy pathway. We herein propose a model by which the geminivirus C4 protein causes NbSnRK1 ß2 degradation via the TbLCYnV C4-NbSnRK1 ß2 interaction to antagonize host antiviral defenses and facilitates viral infection and symptom development in N. benthamiana.

Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78.

Colorectal cancer is one of the most common malignancies worldwide. Although initially effective, patients who receive chemotherapy ultimately experience various complications and develop chemo-resistance, leading to cancer recurrence. Therefore, we aimed to find a drug with good efficacy and low toxicity that could enhance the treatment with 5-Fluorouracil (a commonly used clinical drug) and reduce its dosing. Corilagin, an anti-tumor natural product, has received widespread attention. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal cancer cells and plays a key role in the proliferation, migration and drug resistance of cancer cells. Importantly, GRP78 can affect the apoptosis induced by 5-fluorouracil in CRC cells. In the present study, we determined the synergistic anti-tumor activity of the combination treatment by cell proliferation assay, apoptosis assay, fluorescent staining, cell cycle analysis, WB and PCR assays. This synergistic effect was associated with S-phase blockade, intracellular reactive oxygen species production and downregulation of GRP78. Taken together, our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.

Protective effect of Huangpu Tongqiao capsule against Alzheimer's disease through inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress in vitro and in vivo.

Objectives: Huangpu Tongqiao Capsule (HPTQC) is a traditional Chinese medicine (TCM) that has been used to treat Alzheimer's disease (AD). This study was to explore the pharmacological action and molecular mechanism of HPTQC in the treatment of AD. Methods: The possible targets of HTPQC were predicted by the molecular docking technique. Intraperitoneal injection of D-galactose and bilateral injection of Aß25-35 in hippocampus induced AD rat model. Morris water maze was used to observe learning and memory function. The primary hippocampal neurons were induced by Aß25-35. Moreover, the apoptosis rate of hippocampal nerve cells was detected through AnnexinV/PI double standard staining. The mRNA and protein levels of GRP78, CHOP, Caspase 12, Caspase 9, and Caspase 3 were detected by PCR and western blot. Results: The prediction results suggest that HPTQC may act on GRP78. HPTQC significantly improved the learning and memory function, and decreased neuronal apoptosis in vivo and in vitro. In addition, HPTQC could decrease the mRNA and protein expression levels of GRP78, CHOP, Caspase12, Caspase9, and Caspase3, and the effect trend was consistent with the specific inhibitor of GRP78. Conclusions: HPTQC has a neuroprotective effect against AD by inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress.

Oral Microbiota and Tumor-A New Perspective of Tumor Pathogenesis.

Microorganisms have long been known to play key roles in the initiation and development of tumors. The oral microbiota and tumorigenesis have been linked in epidemiological research relating to molecular pathology. Notably, some bacteria can impact distal tumors by their gastrointestinal or blood-borne transmission under pathological circumstances. Certain bacteria drive tumorigenesis and progression through direct or indirect immune system actions. This review systemically discusses the recent advances in the field of oral microecology and tumor, including the oncogenic role of oral microbial abnormalities and various potential carcinogenesis mechanisms (excessive inflammatory response, host immunosuppression, anti-apoptotic activity, and carcinogen secretion) to introduce future directions for effective tumor prevention.

Study on the Relationship Between Diet, Physical Health and Gut Microflora of Chinese College Students.

Many elements of a modern lifestyle influence the gut microbiota but few studies have explored the effect of physical health level. This study was aimed to explore the relationship between diet, physical health and gut microbiota in Chinese college students. A total of 69 college students were recruited, including 27 college athletes (AS group) and 42 healthy controls (HC group). Fecal samples were collected for 16S rRNA sequencing. According to National Standards for Students' Physical Health (2014 revision), physical fitness measurements, dietary intake and health-related data were collected via questionnaires. ①According to the physical fitness scores, the physical fitness level of AS group was significantly higher than that of HC group (P < 0.05), there were no significant differences between the two groups in the frequency of intake of food. The frequency and duration of physical activity in the AS group were higher than those in the HC group (P < 0.05); ②The proportion and relative abundances of microorganism composition is varying at two groups: on the phylum level, AS group had mainly increased Firmicutes, Actinobacteria and reduced Bacteroidetes, Proteobacteria; on the genus level, AS group had mainly increased Faecalibacterium, Bifidobacterium and reduced Bacteroides; ③The associations with the 10 most abundant bacterial genera and physical fitness, dietary factors were investigated. Changes in the gut microbiota abundance can be sometimes reflective of a physical health status. Loss of the balance of gut microbial populations will lead to flora disorders and diseases. Therefore, further studies are needed to reveal the mechanisms behind the gut microbiota in its potential role.

Texture Image Classification Based on Deep Learning and Wireless Sensor Technology.

The main purpose of the object detection process is to determine the category of the scene object and use the display 3D and 3D frame size. At present, in the case of 3D object detection, we can extract more accurate features by learning a large number of data, and this deep learning network has good results, but there is a very big problem, including the error of input information, extraction error, and so on. Therefore, solving the above problems has become an important direction to promote the rapid development of 3D target detection technology. This paper mainly studies the deep learning wireless sensor technology and also studies the deep learning infrared and visible image fusion. At the same time, based on the introduction of wireless sensor technology and research status, this paper summarizes the existing algorithms. Texture image classification is a more important visual cue in life. Because it will be affected by light intensity, noise size, image scale, and so on. This makes the classification and feature extraction of image scale and texture image more difficult. To solve these problems has become a hot topic of computer vision research in recent years. The shape of the point cloud is completed by using the 3D target detection method to complete the algorithm research. The radar point cloud is extracted by the 3D target detection method, and the radar point group of the overall shape of the object is obtained. The principal component analysis algorithm is used to extract the principal features of the radar point cloud with the complete shape of the object, and the more accurate 3D target frame is obtained after feature adjustment.

Current Status of Probiotics as Supplements in the Prevention and Treatment of Infectious Diseases.

Probiotics play an important role against infectious pathogens via their effects on the epithelium, the production of antimicrobial compounds, and competitive exclusion. Administration of probiotic supplements may reduce the risk of infectious diseases and the use of antibiotics, hence contributing to a reduction or a delay of the development of multi-resistant bacteria. Infection is a constant concern for people who experience recurrent infections, and antibiotic treatment usually fails due to antibiotic resistance. Therefore, an infection can lead to severe illness and hospitalization if left untreated. A growing number of studies have demonstrated promising results for a variety of probiotic strains used to prevent or treat acute and recurrent infectious diseases, but additional standardized clinical research is needed.

Chrysophanol exerts neuroprotective effects via interfering with endoplasmic reticulum stress apoptotic pathways in cell and animal models of Alzheimer's disease.

OBJECTIVES: Chrysophanol (CHR), also well-known as Rhei radix et rhizome, is a crucial component in traditional Chinese medicine. It has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects. However, there are very few studies to establish the potential therapeutic effect of CHR in cell and animal models of Alzheimer's disease (AD). Therefore, we aim to investigate whether CHR could be used as a potential therapeutic approach to patients with AD and further disclose the underlying mechanism. Increasing studies have shown that endoplasmic reticulum (ER) calcium (Ca2+) homeostasis emerges as a central player in AD pathogenesis. Moreover, augmentation of ER stress (ERS) promotes neuronal apoptosis, and excessive oxidative stress is an inducer of ERS. Therefore, we believe that ERS-mediated apoptosis may be one of the causes of AD. METHODS: This study examined the neuroprotective effects of CHR on AD rats and AD cell models and explored its potential mechanism. KEY FINDINGS: CHR could reduce the damage of neurons. In AD cell models, CHR significantly inhibited Aß 25-35-induced neuronal damage, reduced the number of apoptotic cells and improved cell survival rate. Western blot showed that the expression of caspases 3, 9 and 12 was decreased after CHR treatment, and CHR also affected the ERS signalling pathway. In addition, the higher expression of pro-apoptotic proteins in the AD cell model was reduced after CHR treatment by inhibiting GRP78 signalling. Further studies have shown that overexpressed protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) inhibited the regulatory effect of CHR on PERK and weakened the neuroprotective effect of CHR on the AD cell model. CONCLUSIONS: This study revealed a novel mechanism through which CHR plays a neuroprotective role by regulating ERS when it comes to the therapy of AD.

METTL21B is a prognostic biomarker and potential therapeutic target in low-grade gliomas.

A considerable amount of literature has demonstrated that eukaryotic translation elongation factor 1A (eEF1A) is closely related to tumors. As a newly identified lysine specific methyltransferase targeting eEF1A at Lys-165, too little attention has been paid to the function of METTL21B. To determine the potential significance and prognostic value of METTL21B in low grade glioma (LGG), we analyzed the expression, methylation level and copy number variations (CNV) of METTL21B and its effect on prognosis in patients with LGG by 4 public databases in conjunction with experimental examination of LGG patient samples. As a result, we found that high expression, hypomethylation and gain/amplification of CNV of METTL21B were associated with poor prognosis in LGG. The potential functions of METTL21B in LGG may be involved in cell adhesion, angiogenesis and cell proliferation of tumor by enrichment analysis. In addition, METTL21B may facilitate immune evasion of tumor and affect prognosis by mediating macrophage polarization from M1 to M2 and regulating expression of immune checkpoints. Nevertheless, patients with high METTL21B level are likely to have better response to immune checkpoints blockage therapy. Because of its substrate specificity, METTL21B is expected to be a promising target for the treatment of glioma.

Huang-Pu-Tong-Qiao Formula Ameliorates the Hippocampus Apoptosis in Diabetic Cognitive Dysfunction Mice by Activating CREB/BDNF/TrkB Signaling Pathway.

BACKGROUND: Huang-Pu-Tong-Qiao formula (HPTQ), a traditional Chinese medicine (TCM) formula used to improve cognitive impairment. However, the underlying neuroprotective mechanism of HPTQ treated for diabetic cognitive dysfunction (DCD) remains unclear. The purpose of this study was to investigate the neuroprotective mechanism of HPTQ in DCD mice based on molecular docking. METHODS: To investigate the neuroprotective effect of HPTQ in DCD, the Morris water maze (MWM), novel object recognition (NOR) test was used to detect the learning and memory changes of mice; hematoxylin-eosin (HE) staining was used to investigate the damage of hippocampal neurons; the western blot (WB) was used to examine the level of brain-derived neurotrophic factor (BDNF) of hippocampus. To investigate the neuroprotective mechanism of HPTQ in DCD, molecular docking was used to predict the possible target proteins of different active components in HPTQ and then the WB was used to verify the expression of key target proteins in the hippocampus of mice. RESULTS: HPTQ improved the learning and memory ability, hippocampal neuron damage, and the level of BDNF in the hippocampus of the DCD model treated with HFD/STZ for 12 weeks. Besides, the results of molecular docking showed that the main chemical components of HPTQ could be well combined with the targets of Bcl-2-associated X (Bax) and B-cell lymphoma2 (Bcl-2) and caspase-3. The levels of Bax/Bcl-2 protein ratio and caspase-3 increased in the DCD model while the HPTQ inhibited it. In addition, HPTQ restored DCD-induced decline of p-CREB, BDNF, TrkB, and p-Akt in the hippocampus. CONCLUSIONS: These data indicated that HPTQ ameliorates the hippocampus apoptosis in diabetic cognitive dysfunction mice by activating CREB/BDNF/TrkB signaling pathway.

Corrigendum: A Paradigm for Matching Waking Events Into Dream Reports.

[This corrects the article DOI: 10.3389/fpsyg.2020.01430.].

An increase in DNA G-quadruplex formation in acute myelocytic leukemia is detected by a supramolecular probe.

Acute myeloid leukemia (AML) is a common acute leukemia in both adults and children, with poor early detection and diagnosis. Therefore, identifying new indicators for AML detection is significant for effective treatment. Here, we developed a supramolecular probe that exhibits high specificity and sensitivity to G-quadruplex structures in physiological buffer solution, chromosomes, and cells. Using this probe, we tested the DNA extracted from different types of cells and found that the DNA extracted from human acute myeloid leukemia cells HL-60 and KG-1 enhanced the probe fluorescence more significantly than the DNA extracted from other cells. This phenomenon may be related to a large number of G-quadruplexes in acute myeloid leukemia cells, implicating that G-quadruplex levels may be a potential indicator for the detection of acute myeloid leukemia.

Integration of waking experience through dreams considered in light of individual differences in implicit learning ability.

The present study explored whether individual differences in implicit learning were related to the incorporation of waking events into dreams. Participants (N = 60) took part in a sequence learning task, a measure of implicit learning ability. They were then asked to keep a record of their waking experiences (personally significant events [PSEs]/major concerns), as well as their nightly dreams for a week. Of these, the responses of 51 participants were suitable for further analysis in which participants themselves and three independent judges rated the correlation between waking events and dreams of the same day. Implicit learning ability was found to significantly correlate with the incorporation of PSEs into dreams. The present results may lend support to the Horton and Malinowski autobiographical memory (AM) model, which accounts for the activation of memories in dreams as a reflection of sleep-dependent memory consolidation processes that focusses in particular on the hyperassociative nature of AM during sleep.

Research Progress of Alzheimer's Disease Therapeutic Drugs: Based on Renin-Angiotensin System Axis.

It is widely recognized that Alzheimer's disease (AD) has a complicate link to renin-angiotensin system (RAS). It is known that cerebrovascular disease has some connections with AD, but most of the studies are still conducted in parallel or independently. Although previous research came up with large number of hypotheses about the pathogenesis of AD, it does not include the mechanism of RAS-related regulation of AD. It has been found that many components of RAS have been changed in AD. For example, the multifunctional and high-efficiency vasoconstrictor Ang II and Ang III with similar effects are changed under the action of other RAS signal peptides; these signal peptides are believed to help improve nerve injury and cognitive function. These changes may lead to neuropathological changes of AD, and progressive defects of cognitive function, which are association with some hypotheses of AD. The role of RAS in AD gradually attracts our attention, and RAS deserved to be considered carefully in the pathogenesis of AD. This review discusses the mechanisms of RAS participating in the three current hypotheses of AD: neuroinflammation, oxidative stress and amyloid-ß protein (Aß) hypothesis, as well as the drugs that regulate RAS systems already in clinical or in clinical trials. It further demonstrates the importance of RAS in the pathogenesis of AD, not only because of its multiple aspects of participation, which may be accidental, but also because of the availability of RAS drugs, which can be reused as therapies of AD.

Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3-mediated E2F1 activation.

BACKGROUND: Growing evidences have been revealing that long noncoding RNAs are vital factors in oncogenesis and tumor development. Among them, cancer susceptibility candidate 11 (CASC11) has displayed an impressively essential role in various kinds of cancers including hepatocellular carcinoma (HCC). Nevertheless, its role and potential mechanism in HCC still remain to be fully investigated. METHODS: CASC11 expression level was evaluated by real-time polymerase chain reaction, western blotting, and in situ hybridization staining in HCC patients, and its prognostic effect was analyzed. The role of CASC11 in HCC tumorigenesis and progression was investigated by cell proliferation assay, transwell assay, extracellular acidification rate, western blotting, flow cytometry, and an in vivo xenograft model. The interactions among CASC11, E2F transcription factor 1 (E2F1), and eukaryotic translation initiation factor 4A3 (EIF4A3) were explored by using quantitative reverse transcriptase polymerase chain reaction, western blotting, RNA-binding protein immunoprecipitation assay, and chromatin immunoprecipitation assays. RESULTS: Upregulation of CASC11 was confirmed in HCC tissues and associated with poor prognosis. Loss of function assays showed inhibition of CASC11 expression suppressed HCC cells proliferation, mobility, and glucose metabolism and promoted apoptosis. E2F1 expression significantly decreased after inhibition of CASC11. Rescue experiments illustrated that E2F1 overexpression alleviated the suppression of CASC11 inhibition on HCC progression in vitro and in vivo. Mechanistically, CASC11 recruited EIF4A3 to enhance the stability of E2F1 mRNA. CASC11 and E2F1 impacted the activation of the NF-κB signaling and PI3K/AKT/mTOR pathway and further regulated the expression PD-L1 that is an important target of immunotherapy. In addition, we identified YY1 could modulate CASC11 expression by binding to its promoter. CONCLUSIONS: Our data revealed that CASC11 promoted the progression of HCC by means of EIF4A3-mediated E2F1 upregulation, indicating CASC11 is a promising diagnostic biomarker and therapeutic target for HCC.

Chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CDCAG) in patients with relapsed/refractory acute myeloid leukemia: a single-arm, phase 1/2 study.

BACKGROUND: Epigenetic mechanisms play an important role in the chemoresistance of acute myeloid leukemia (AML). The clinical response to epigenetic modifier-based chemotherapy in patients with relapsed/refractory AML (r/r AML) is unclear. This multicenter clinical trial evaluated the safety and efficacy of epigenetic modifiers (chidamide and decitabine) in combination with aclarubicin, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in patients with r/r AML. RESULTS: Adult patients with r/r AML were treated with chidamide, decitabine, cytarabine, aclarubicin, and G-CSF (CDCAG). The primary measures were overall response (OR), overall survival (OS), and safety. Next-generation sequencing was performed to analyze the correlation between gene mutations and response. A total of 93 patients with r/r AML were enrolled. Overall, 24 patients had a complete remission (CR) and 19 patients achieved CR with incomplete blood count recovery (CRi). The overall response rate (ORR) was 46.2%. The overall survival of these 43 patients who achieved CR/CRi was significantly longer than that of patients who failed to achieve remission (563 vs 152 days, P < 0.0001). Of the patients with mutations in epigenetic and transcription factor-related genes, but without internal tandem duplications in FMS-like tyrosine kinase3 (FLT3-ITDs), 55.6% achieved CR/CRi, whereas the ORR was 28.2% for patients with mutations in other genes. CONCLUSIONS: The CDCAG regimen was well tolerated and effective in r/r AML. Patients with epigenetic and transcription factor-related gene mutations, but without FLT3-ITD mutations, may benefit from this regimen. TRIAL REGISTRATION: Clinical Trials, NCT02886559 . Registered 01 September 2016.

The Regulating Mechanism of Chrysophanol on Protein Level of CaM-CaMKIV to Protect PC12 Cells Against Aß25-35-Induced Damage.

OBJECTIVE: To investigate the neuroprotective effect of chrysophanol (CHR) on PC12 treated with Aß25-35, and the involved mechanism. METHODS: After the establishment of an AD cell model induced by Aß25-35, the cell survival rate was detected by MTT, cell apoptosis was assayed by Hoechst 33342 staining, mRNA expressions of calmodulin (CaM), calcium/calmodulin-dependent protein kinase kinase (CaMKK), calcium/calmodulin-dependent protein kinase IV (CaMKIV) and tau (MAPT; commonly known as tau) were determined by qRT-PCR, and protein levels of CaM, CaMKK, CaMKIV, phospho-CaMKIV (p-CaMKIV), tau and phospho-tau (p-tau) were detected by Western blot analysis. RESULTS: When pretreated with CHR before exposure to Aß25-35, PC12 cells showed that increased cell viability and reduced apoptosis. The qRT-PCR results indicated that the deposition of Aß25-35 triggers a decrease in levels of CaM, CaMKK, CaMKIV, and tau in PC12 cells. In addition, Western blot results also suggested that Aß25-35 decreases the protein expression of CaM, CaMKK, CaMKIV, p-CaMKIV, and the ratio of p-tau to tau in PC12 cells. However, the above effects were significantly alleviated after the treatment of CHR. CONCLUSION: CHR plays a neuroprotective role in AD though decreasing the protein level of CaM-CaMKK-CaMKIV and the expression of p-tau downstream.

A Paradigm for Matching Waking Events Into Dream Reports.

In this study, participants recorded their waking events (Personal significant events, PSEs/Major concerns, MCs) and dream reports for 7 days. These events and dreams were paired by the same day (216 PSEs-dreams pairs and 215 MCs-dreams pairs). Then participants were instructed to both find similar features (characters, objects, locations, actions, emotions, and themes) of their events-dreams pairs and give a match score of their events-dreams pairs. Besides, we proposed a method for independent judges to match waking events into dreams (the external ratings). The rating standard of the external-ratings was to look for similar behaviors between events and dreams. Based on this rating standard, three independent judges were instructed to rate participants' events-dreams pairs. Firstly, we compared the two kinds of methods of self-ratings. Spearman correlations showed that the two methods were significantly correlated with each other. These results suggested that the sum of different kinds of similar features could be used to represent self-ratings reported of the degree of the correlation between a waking event and a dream. Regression correlations showed that for PSEs-dreams pairs, characters, actions, emotions, and themes were similar features that affected the degree of the correlation between an event and a dream of the same day, and for MCs-dreams pairs, characters, locations, emotions, and themes were similar features that affected the degree of the correlation between an event and a dream of the same day. These results suggested that different kinds of similar features had different influence on the self-ratings' evaluation for the degree of matching between waking event and dream. Secondly, we compared the rating results of the self-ratings and the rating results of the external-ratings. Spearman correlations showed that the results of the self-ratings were significantly correlated with the results of the external-ratings. So this study's method for the external ratings may be suitable for future studies. Besides, as the external ratings of this study can rate dream metaphors, we also made a short discussion on dream metaphors. Future studies can use the method to explore dream metaphors.

Chrysophanol improves memory ability of d-galactose and Aß25-35 treated rat correlating with inhibiting tau hyperphosphorylation and the CaM-CaMKIV signal pathway in hippocampus.

This study was aimed to investigate the effect of Chrysophanol (CHR) on Alzheimer's disease. We also attempted to understand the potential mechanisms. An Alzheimer's disease rat model was established using an intraperitoneal injection of d-galactose combined with an intracerebral injection of amyloid-ß peptide (25-35), and the effect of CHR on the learning and memory ability, the hippocampal neurons change, the ultrastructure of the hippocampal CA1 region, the protein levels of CaM, CaMKK, CaMKIV, p-CaMKIV and p-tau in the hippocampus of rats were studied. The results showed that CHR significantly improved the cognitive deficits, alleviated hippocampal neurons damage, prevented the ultrastructure alteration of neurons in hippocampal CA1 region, and reduced the protein levels of CaM, CaMKK, p-CaMKIV and p-tau in the hippocampus of AD rats. These results suggested that Chrysophanol could improve memory ability of Alzheimer's disease rat by inhibiting tau hyperphosphorylation and the CaM-CaMKIV signal pathway.

Very late onset post-transplant diffuse large B cell lymphoma in a liver transplant recipient with hepatitis B: A case report.

RATIONALE: Post transplantation lymphoproliferative disorder (PTLD) is a rare but severe complication. Epstein-Barr virus (EBV) is considered an important pathogen for PTLD and EBV deoxyribonucleic acid (DNA) load is widely monitored to detect PTLD early. Hepatitis B virus (HBV) infection is rarely reported to be related with PTLD. We report a case of EBV negative (EBV), HBV positive (HBV) diffuse large B cell lymphoma in a patient 12 years after liver transplantation. PATIENT CONCERNS AND DIAGNOSIS: A 52-year-old man complained of worsening appetite, abdominal distension, and pruritus. Abdominal computed tomography (CT) detected a huge retroperitoneal mass and pathology of the fine needle biopsy established the diagnosis of diffuse large B cell lymphoma. Virology showed active hepatitis B viral duplication and EBV DNA was negative. INTERVENTION: Treatment modalities for this patient included: reduction and subsequent cessation of immunosuppression; antiviral therapy for HBV with entecavir and adefovir; conventional chemotherapy consisting of cyclophosphamide, epirubicin, vindesine, and prednisone, followed by radiotherapy. He achieved complete remission (CR) and was kept on entecavir treatment afterwards. OUTCOMES: He has been in remission for 2 years. LESSONS: HBV infection might have played some role in this very late onset EBV PTLD patient. Therefore, HBV serology and HBV load should be monitored during the follow-up of HBV surface antigen positive (HBsAg) transplant recipients and life-long antiviral therapy is required.