Sweet syndrome induced by FLT3 inhibitors: case report and literature review.

BACKGROUND: Acute febrile neutrophilic dermatosis, also commonly referred to as Sweet syndrome, is often associated with tumors, infections, immune disorders and medications. FLT3 inhibitor-induced Sweet syndrome is a rare complication. METHODS AND RESULTS: We report a patient with relapsed and refractory acute monocytic leukemia harboring high-frequency FLT3-ITD and DNMT3a mutations. The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. The leukemia patient achieved remission after 1 month of treatment. However, Sweet syndrome induced by gilteritinib, which was confirmed by skin biopsy, developed during induction therapy. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. CONCLUSION: Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

PMFFNet: A hybrid network based on feature pyramid for ovarian tumor segmentation.

Ovarian cancer is a highly lethal malignancy in the field of oncology. Generally speaking, the segmentation of ovarian medical images is a necessary prerequisite for the diagnosis and treatment planning. Therefore, accurately segmenting ovarian tumors is of utmost importance. In this work, we propose a hybrid network called PMFFNet to improve the segmentation accuracy of ovarian tumors. The PMFFNet utilizes an encoder-decoder architecture. Specifically, the encoder incorporates the ViTAEv2 model to extract inter-layer multi-scale features from the feature pyramid. To address the limitation of fixed window size that hinders sufficient interaction of information, we introduce Varied-Size Window Attention (VSA) to the ViTAEv2 model to capture rich contextual information. Additionally, recognizing the significance of multi-scale features, we introduce the Multi-scale Feature Fusion Block (MFB) module. The MFB module enhances the network's capacity to learn intricate features by capturing both local and multi-scale information, thereby enabling more precise segmentation of ovarian tumors. Finally, in conjunction with our designed decoder, our model achieves outstanding performance on the MMOTU dataset. The results are highly promising, with the model achieving scores of 97.24%, 91.15%, and 87.25% in mACC, mIoU, and mDice metrics, respectively. When compared to several Unet-based and advanced models, our approach demonstrates the best segmentation performance.

Targeting PRAME for acute myeloid leukemia therapy.

Despite significant progress in targeted therapy for acute myeloid leukemia (AML), clinical outcomes are disappointing for elderly patients, patients with less fit disease characteristics, and patients with adverse disease risk characteristics. Over the past 10 years, adaptive T-cell immunotherapy has been recognized as a strategy for treating various malignant tumors. However, it has faced significant challenges in AML, primarily because myeloid blasts do not contain unique surface antigens. The preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is abnormally expressed in AML and does not exist in normal hematopoietic cells. Accumulating evidence has demonstrated that PRAME is a useful target for treating AML. This paper reviews the structure and function of PRAME, its effects on normal cells and AML blasts, its implications in prognosis and follow-up, and its use in antigen-specific immunotherapy for AML.

Myelomonocytic and monocytic acute myeloid leukemia demonstrate comparable poor outcomes with venetoclax-based treatment: a monocentric real-world study.

Venetoclax (VEN), a BCL-2 inhibitor, has transformed treatment strategies for elderly and unfit acute myeloid leukemia (AML) patients by significantly improving response rates and survival. However, the predictive factors for VEN efficacy differ from traditional chemotherapy. The clinical relevance of the FAB (French-American-British) monocytic subtype, including M4 and M5, has been debated as a marker for VEN resistance. This real-world study examined 162 newly diagnosed (ND) and 85 relapsed/refractory (R/R) AML patients who received VEN-based therapy at West China Hospital, Sichuan University, from January 2019 to January 2023. We retrospectively collected clinical and treatment data from electronic medical records. The median age of the cohort was 55.5 years (range: 16.5-83.5). The composite complete remission (cCR) rate in the entire cohort was 60.7%. Specifically, among newly diagnosed (ND) patients, FAB monocytic subtypes exhibited lower cCR compared to non-monocytic subtypes (55.1% vs. 76.3%, P = 0.007). Additionally, there were no significant differences observed between M4 and M5 subtypes, both in the ND group (61.7% vs. 40.9%, p = 0.17) and the R/R group (38.2% vs. 40%, p > 0.9). Furthermore, the median follow-up was 238 (range: 7-1120) days. ND patients with monocytic subtypes had shorter overall survival compared to non-monocytic subtypes (295 days vs. not reached, p = 0.0017). Conversely, R/R patients showed no such difference (204 vs. 266 days, p = 0.72). In summary, our study suggests that the FAB monocytic subtype can predict VEN resistance and shorter survival in ND AML patients. Moreover, there is no significant distinction between M4 and M5 subtypes.

Identification of Critical Links Based on Electrical Betweenness and Neighborhood Similarity in Cyber-Physical Power Systems.

Identifying critical links is of great importance for ensuring the safety of the cyber-physical power system. Traditional electrical betweenness only considers power flow distribution on the link itself, while ignoring the local influence of neighborhood links and the coupled reaction of information flow on energy flow. An identification method based on electrical betweenness centrality and neighborhood similarity is proposed to consider the internal power flow dynamic influence existing in multi-neighborhood nodes and the topological structure interdependence between power nodes and communication nodes. Firstly, for the power network, the electrical topological overlap is proposed to quantify the vulnerability of the links. This approach comprehensively considers the local contribution of neighborhood nodes, power transmission characteristics, generator capacity, and load. Secondly, in communication networks, effective distance closeness centrality is defined to evaluate the importance of communication links, simultaneously taking into account factors such as the information equipment function and spatial relationships. Next, under the influence of coupled factors, a comprehensive model is constructed based on the dependency relationships between information flow and energy flow to more accurately assess the critical links in the power network. Finally, the simulation results show the effectiveness of the proposed method under dynamic and static attacks.

Drug repurposing: insights into the antimicrobial effects of AKBA against MRSA.

Staphylococcus aureus is a major threat in infectious diseases due to its varied infection types and increased resistance. S. aureus could form persister cells under certain condition and could also attach on medical apparatus to form biofilms, which exhibited extremely high resistance to antibiotics. 3-Acetyl-11-keto-beta-boswellic acid (AKBA) is a well-studied anti-tumor and antioxidant drug. This study is aimed to determine the antimicrobial effects of AKBA against S. aureus and its persister cells and biofilms. The in vitro antimicrobial susceptibility of AKBA was assessed by micro-dilution assay, disc diffusion assay and time-killing assay. Drug combination between AKBA and conventional antibiotics was detected by checkerboard assay. And the antibiofilm effects of AKBA against S. aureus were explored by crystal violet staining combined with SYTO/PI probes staining. Next, RBC lysis activity and CCK-8 kit were used to determine the cytotoxicity of AKBA. In addition, murine subcutaneous abscess model was used to assess the antimicrobial effects of AKBA in vivo. Our results revealed that AKBA was found to show effective antimicrobial activity against methicillin-resistant S. aureus (MRSA) with the minimal inhibitory concentration of 4-8 µg/mL with undetectable cytotoxicity. And no resistant mutation was induced by AKBA after 20 days of consecutive passage. Further, we found that AKBA could be synergy with gentamycin or amikacin against S. aureus and its clinical isolates. By crystal violet and SYTO9/PI staining, AKBA exhibited strong biofilm inhibitory and eradication effects at the concentration of 1 ~ 4 µg/mL. In addition, the effective antimicrobial effect was verified in vivo in a mouse model. And no detectable in vivo toxicity was found. These results indicated that AKBA has great potential to development as an alternative treatment for the refractory S. aureus infections.

High dose Vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC.

Vitamin C (VitC) presents excellent anti-tumor effect for long time. Recently, high dose VitC achieved by intravenous administration manifests superior anti-tumor effect. However, the functions and detailed mechanisms of high dose VitC's role in cancer immunity are not fully understood. This study investigates the effect of high dose VitC on PD-L1 expression in triple negative breast cancer (TNBC) and the potential mechanism. Results showed VitC inhibited PD-L1 expression in breast cancer cell lines and enhanced anti-tumor effects of T cells. Furthermore, we found VitC inhibited PD-L1 transcription through ROS-pSTAT3 signal pathways. Consistent with in vitro results, in vivo study showed VitC suppressed tumor growth in immunocompetent mice and enhanced CD8+ T cells infiltration and function in tumor microenvironment. Our findings identify the effects of high dose VitC on PD-L1 expression and provide a rationale for the use of high dose VitC as immunomodulator for cancer therapy.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Inverse Problem Algorithm-Based Time-Resolved Imaging of Head and Neck Computed Tomography Angiography Contrast Kinetics with Clinical Testification.

This study mitigated the challenge of head and neck CT angiography by IPA-based time-resolved imaging of contrast kinetics. To this end, 627 cerebral hemorrhage patients with dizziness, brain aneurysm, stroke, or hemorrhagic stroke diagnosis were randomly categorized into three groups, namely, the original dataset (450), verification group (112), and in vivo testified group (65), in the Affiliated BenQ Hospital of Nanjing Medical University. In the first stage, seven risk factors were assigned: age, CTA tube voltage, body surface area, heart rate per minute, cardiac output blood per minute, the actual injected amount of contrast media, and CTA delayed trigger timing. The expectation value of the semi-empirical formula was the CTA number of the patient's left artery (LA). Accordingly, 29 items of the first-order nonlinear equation were calculated via the inverse problem analysis (IPA) technique run in the STATISTICA 7.0 program, yielding a loss function and variance of 3.1837 and 0.8892, respectively. A dimensionless AT was proposed to imply the coincidence, with a lower AT indicating a smaller deviation between theoretical and practical values. The derived formula was confirmed for the verification group of 112 patients, reaching high coincidence, with average ATavg and standard deviation values of 3.57% and 3.06%, respectively. In the second stage, the formula was refined to find the optimal amount of contrast media for the CTA number of LA approaching 400. Finally, the above procedure was applied to head and neck CTA images of the third group of 65 patients, reaching an average CTA number of LA of 407.8 ± 16.2 and finding no significant fluctuations.

The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China.

BACKGROUND: The clinical significance of protein tyrosine phosphatase nonreceptor type 11 mutation (PTPN11mut ) in acute myeloid leukemia (AML) is underestimated. METHODS: We collected the data of AML patients with mutated PTPN11 and wild-type PTPN11 (PTPN11wt ) treated at our hospital and analyzed their clinical characteristics and prognosis. RESULTS: Fifty-nine PTPN11mut and 124 PTPN11wt AML patients were included. PTPN11mut was more common in myelomonocytic and monocytic leukemia, and was more likely to co-mutate with KRAS, KMT2C, NRAS, U2AF1, NOTCH1, IKZF1, and USH2A mutations than PTPN11wt . The overall survival for AML patients with PTPN11mut was significantly shorter than that for those with PTPN11wt (p = 0.03). The negative impact of PTPN11mut on overall survival was pronounced in the "favorable" and "intermediate" groups of ELN2017 risk stratification, as well as in the wild-type NPM1 group (p = 0.01, p = 0.01, and p = 0.04). CONCLUSION: PTPN11mut is associated with distinct clinical and molecular characteristics, and adverse prognosis in AML patients.

Allogeneic cord blood regulatory T cells decrease dsDNA antibody and improve albuminuria in systemic lupus erythematosus.

Background: Lupus nephritis (LN) constitutes the most severe organ manifestations of systemic lupus erythematosus (SLE), where pathogenic T cells have been identified to play an essential role in 'helping' B cells to make autoantibodies and produce inflammatory cytokines that drive kidney injury in SLE. Regulatory T cells (Tregs), responsible for decreasing inflammation, are defective and decreased in SLE and have been associated with disease progression. We hypothesize that treatment with allogeneic, healthy Tregs derived from umbilical cord blood (UCB) may arrest such an inflammatory process and protect against kidney damage. Methods: UCB-Tregs function was examined by their ability to suppress CellTrace Violet-labeled SLE peripheral blood mononuclear cells (PBMCs) or healthy donor (HD) conventional T cells (Tcons); and by inhibiting secretion of inflammatory cytokines by SLE PBMCs. Humanized SLE model was established where female Rag2-/-γc-/- mice were transplanted with 3 × 106 human SLE-PBMCs by intravenous injection on day 0, followed by single or multiple injection of UCB-Tregs to understand their impact on disease development. Mice PB was assessed weekly by flow cytometry. Phenotypic analysis of isolated cells from mouse PB, lung, spleen, liver and kidney was performed by flow cytometry. Kidney damage was assessed by quantifying urinary albumin and creatinine secretion. Systemic disease was evaluated by anti-dsDNA IgG Ab analysis as well as immunohistochemistry analysis of organs. Systemic inflammation was determined by measuring cytokine levels. Results: In vitro, UCB-Tregs are able to suppress HD Tcons and pathogenic SLE-PBMCs to a similar extent. UCB-Tregs decrease secretion of several inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, IL-17A, and sCD40L by SLE PBMCs in a time-dependent manner, with a corresponding increase in secretion of suppressor cytokine, IL-10. In vivo, single or multiple doses of UCB-Tregs led to a decrease in CD8+ T effector cells in different organs and a decrease in circulating inflammatory cytokines. Improvement in skin inflammation and loss of hair; and resolution of CD3+, CD8+, CD20+ and Ki67+ SLE-PBMC infiltration was observed in UCB-Treg recipients with a corresponding decrease in plasma anti-double stranded DNA IgG antibody levels and improved albuminuria. Conclusions: UCB-Tregs can decrease inflammatory burden in SLE, reduce auto-antibody production and resolve end organ damage especially, improve kidney function. Adoptive therapy with UCB-Tregs should be explored for treatment of lupus nephritis in the clinical setting.

Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia.

Here we report a new fusion gene, STRN3-RARA, in acute promyelocytic leukemia (APL). It cooperates with UTX deficiency to drive full-blown APL in mice. Although STRN3-RARA leukemia quickly relapses after all-trans retinoic acid treatment, it can be restrained by cepharanthine.

Multi-Focus Image Fusion via Distance-Weighted Regional Energy and Structure Tensor in NSCT Domain.

In this paper, a multi-focus image fusion algorithm via the distance-weighted regional energy and structure tensor in non-subsampled contourlet transform domain is introduced. The distance-weighted regional energy-based fusion rule was used to deal with low-frequency components, and the structure tensor-based fusion rule was used to process high-frequency components; fused sub-bands were integrated with the inverse non-subsampled contourlet transform, and a fused multi-focus image was generated. We conducted a series of simulations and experiments on the multi-focus image public dataset Lytro; the experimental results of 20 sets of data show that our algorithm has significant advantages compared to advanced algorithms and that it can produce clearer and more informative multi-focus fusion images.

Prognostic value of IDH2R140 and IDH2R172 mutations in patients with acute myeloid leukemia: a systematic review and meta-analysis.

BACKGROUND: Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we performed a meta-analysis to assess their prognostic value. METHODS: Eligible studies were systematically searched from PubMed, Embase, the Cochrane Library and Chinese databases up to June 1, 2022. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) to carry out a meta-analysis by a fixed effect model or random effect model according to the heterogeneity between studies. RESULTS: A total of 12725 AML patients from 11 studies were included in this meta-analysis, of which 1111 (8.7%) and 305 (2.4%) had IDH2R140 and IDH2R172 mutations, respectively. The results revealed that both IDH2R140 and IDH2R172 mutations had no significant effect on OS (IDH2R140: HR = 0.92, 95% CI: 0.77-1.10, P = 0.365; IDH2R172: HR = 0.91, 95% CI: 0.65-1.28, P = 0.590) or PFS (IDH2R140: HR = 1.02, 95% CI: 0.75-1.40, P = 0.881; IDH2R172: HR = 1.31, 95% CI: 0.78-2.22, P = 0.306) in AML patients. Subgroup analysis of AML patients with IDH2R140 mutation revealed that studies from the USA (HR = 0.60, 95% CI: 0.41-0.89, P = 0.010) and ≤ 50 years old (HR = 0.63, 95% CI: 0.50-0.80, P = 0.000) had longer OS. However, studies from Sweden (HR = 1.94, 95% CI: 1.07-3.53, P = 0.030) had shorter OS. Meanwhile, subgroup analysis of AML patients with IDH2R172 mutation showed that studies from Germany/Austria (HR = 0.76, 95% CI: 0.61-0.94, P = 0.012) and from Sweden (HR = 0.22, 95% CI: 0.07-0.74, P = 0.014) had longer OS, whereas studies from the UK (HR = 1.49, 95% CI: 1.13-1.96, P = 0.005) and studies with nonmultivariate analysis of data type (HR = 1.35, 95% CI: 1.06-1.73, P = 0.014) had shorter OS. In addition, our study also found that patients with IDH2R140 mutation had significantly longer OS (HR = 0.61, 95% CI: 0.39-0.96, P = 0.032) and PFS (HR = 0.31, 95% CI: 0.18-0.52, P = 0.021) than patients with IDH2R172 mutation, despite some degree of heterogeneity. CONCLUSIONS: This meta-analysis demonstrates that IDH2R140 mutation improves OS in younger AML patients and that the prognostic value of IDH2R172 mutation is significantly heterogeneous. Differences in region and data type have a significant impact on the prognosis of AML patients with IDH2R140 and/or IDH2R172 mutations. Additionally, AML patients with IDH2R140 mutation have a better prognosis than those with IDH2R172 mutations, albeit with some degree of heterogeneity.

A Lightweight Feature Distillation and Enhancement Network for Super-Resolution Remote Sensing Images.

Super-resolution (SR) images based on deep networks have achieved great accomplishments in recent years, but the large number of parameters that come with them are not conducive to use in equipment with limited capabilities in real life. Therefore, we propose a lightweight feature distillation and enhancement network (FDENet). Specifically, we propose a feature distillation and enhancement block (FDEB), which contains two parts: a feature-distillation part and a feature-enhancement part. Firstly, the feature-distillation part uses the stepwise distillation operation to extract the layered feature, and here we use the proposed stepwise fusion mechanism (SFM) to fuse the retained features after stepwise distillation to promote information flow and use the shallow pixel attention block (SRAB) to extract information. Secondly, we use the feature-enhancement part to enhance the extracted features. The feature-enhancement part is composed of well-designed bilateral bands. The upper sideband is used to enhance the features, and the lower sideband is used to extract the complex background information of remote sensing images. Finally, we fuse the features of the upper and lower sidebands to enhance the expression ability of the features. A large number of experiments show that the proposed FDENet both produces less parameters and performs better than most existing advanced models.

RNA sequencing of myeloid sarcoma, shed light on myeloid sarcoma stratification.

BACKGROUND: Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens. METHODS: Here, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA-seq) on formalin-fixed paraffin-embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities-based risk stratification using fusion genes and gene mutations. RESULTS: A total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1-RUNX1T1, CBFß-MYH11, ETV6-MECOM, FUS-ERG, and PICALM-MLLT10. The prognosis in the adverse-risk group was significantly worse than that in the favorable/intermediate-risk group (median survival: 12 months vs. not reached; p = 0.0004). CONCLUSION: These results indicated the efficacy of RNA-seq using FFPE-derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.

Sparse Representation-Based Multi-Focus Image Fusion Method via Local Energy in Shearlet Domain.

Multi-focus image fusion plays an important role in the application of computer vision. In the process of image fusion, there may be blurring and information loss, so it is our goal to obtain high-definition and information-rich fusion images. In this paper, a novel multi-focus image fusion method via local energy and sparse representation in the shearlet domain is proposed. The source images are decomposed into low- and high-frequency sub-bands according to the shearlet transform. The low-frequency sub-bands are fused by sparse representation, and the high-frequency sub-bands are fused by local energy. The inverse shearlet transform is used to reconstruct the fused image. The Lytro dataset with 20 pairs of images is used to verify the proposed method, and 8 state-of-the-art fusion methods and 8 metrics are used for comparison. According to the experimental results, our method can generate good performance for multi-focus image fusion.

Impact of NOTCH1 polymorphisms on liver cancer in a Chinese Han population.

NOTCH1, a member of the Notch family, is up-expression in advanced liver cancer (LC) patients and is associated with tumor sizes, tumor stage, metastasis, and invasion. A few studies have discovered the contribution of NOTCH1 variants to LC risk. Our purpose was to assess the relationship of NOTCH1 rs10521, rs2229971, and rs4489420 to LC risk. We enrolled 709 LC patients and 708 healthy controls. Genotyping was determined through the Agena MassARRAY system. Multiple genetic models by logistic regression were useful for odds ratios (ORs) with 95% confidence intervals (CIs). Rs10521-G (p = 0.009, OR = 0.75, 95% CI: 0.61-0.93), rs2229971-A (p = 0.023, OR = 0.81, 95% CI: 0.67-0.97), and rs4489420-A (p = 0.014, OR = 0.38, 95% CI: 0.16-0.85) might be protective factors for LC occurrence in the Chinese Han population, especially rs10521 and rs2229971 (false-positive report probability (FPRP) <0.2 and statistical power >90%). Interestingly, stratified analysis displayed that the contribution of NOTCH1 polymorphisms to LC risk might be associated with gender, age, smoking, and drinking. Our data first determined that NOTCH1 rs10521-G, rs2229971-A, and rs4489420-A might be protective factors for LC susceptibility.

Chronic active Epstein-Barr virus infection involving gastrointestinal tract with hemophagocytic lymphohistiocytosis.

Chronic active EBV infection (CAEBV) is a lymphoproliferative disorder of T- or NK-cell type in Asian countries. CAEBV involving the gastrointestinal tract (GI CAEBV) is a rare condition with poor prognosis that may rapidly progress with hemophagocytic lymphohistiocytosis (HLH) and life-threatening complications such as GI bleeding and/or perforation. The approach to CAEBV with GI tract involvement (GI CAEBV) is still an unmet clinical need. In this case series study, we summarized the clinical features, treatment, and prognosis of seven cases of GI CAEBV with HLH, particularly focusing on its prognosis and the possible salvage therapy combining surgery, novel therapeutic agents, and/or autologous(auto-) hematopoietic stem cell transplantation (HSCT) based on successful cases from our center. GI CAEBV is often misdiagnosed as inflammatory bowel diseases and certain infections. The key to its early recognition is the integrative consideration of its systemic manifestation, serum virology, endoscopic, and imaging findings along with pathology. Surgical intervention should not be hesitated when life-threatening GI complications occur. Resection of the involved bowel segment is an effective way of controlling bleeding and reducing tumor burden. In addition to upfront allogeneic HSCT, new therapeutic modalities including PD-1 antibody and auto-HSCT may be effective in certain patients.

PIK3R3 Missense and NOTCH2 Synonymous Single Nucleotide Polymorphisms Are Associated with Liver Cancer.

BACKGROUND: Single nucleotide polymorphism (SNP) of candidate genes also affects the occurrence and prognosis of liver cancer. We mainly explored the effects of PIK3R3 and NOTCH2 polymorphisms on liver cancer risk among Chinese people. METHODS: Four SNPs (rs785468, rs785467, rs3795666, and rs17024525 in PIK3R3 and NOTCH2) from 709 liver cancer patients and 700 healthy controls were genotyped using the Agena MassARRAY system. The correlation between SNPs and liver cancer risk was evaluated using logistic regression analysis. The SNP-SNP interactions were conducted by the multifactor dimensionality reduction method. RESULTS: The results revealed that PIK3R3-rs785467 reduced the likelihood of liver cancer among Chinese Han people (p < 0.05). In addition, PIK3R3-rs785467 decreased the susceptibility to liver cancer in different populations (females, non-smokers, and age >55 years, p < 0.05). NOTCH2-rs3795666 reduced the susceptibility to liver cancer among males, drinkers, and patients aged >55 years (p < 0.05). CONCLUSIONS: Our results demonstrate that PIK3R3-rs785476 and NOTCH2-rs3795666 polymorphisms are responsible for decreasing the susceptibility of liver cancer development in the Chinese Han population.