A life-threatening, massive subcutaneous hematoma caused by trauma in a patient with neurofibromatosis type 1: a case report and literature review.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that can give rise to the formation of vascular lesions in affected individuals. These lesions, whether occurring spontaneously or as a result of trauma, have the potential to cause severe and even fatal hemorrhage. Case description: We presented a case demonstrating the most extensive hematoma ever documented in a patient with NF1, resulting from a minor trauma. He experienced hemodynamic instability due to severe anemia. Arteriography revealed a rupture in the intercostal artery, which was successfully treated through interventional embolization to stop the hemorrhage. Additionally, we implemented a refined surgical approach, beginning with suturing, followed by the meticulous resection of necrotic and aberrant tissues, thereby markedly diminishing bleeding. Conclusion: Minor trauma may cause severe bleeding in patients with NF1, which can be life-threatening. Timely diagnosis of NF1 and effective hemostatic techniques are key to successful treatment.

Anchoring flap suture technique to repair a wound with exposed bone after hip disarticulation: a case report and brief review of the literature.

BACKGROUND: In specific clinical scenarios characterized by poor tissue conditions surrounding a wound, achieving stable flap fixation with standard sutures can be challenging. The anchoring flap suture technique, which is commonly used for soft tissue-to-bone attachment in cases of injury, may be an alternative and effective approach. CASE REPORT: This report describes the successful application of the anchoring flap suture technique to repair a wound with exposed bone in a 39-year-old female patient. She presented with a 7% TBSA wound of the left trunk following hip disarticulation. After 4 operations, a wound with exposed iliac bone remained. Given the compromised condition of the tissues surrounding the exposed bone, the authors opted to anchor a local flap directly to the exposed bone. Steady flap fixation was achieved using the anchoring flap suture method, resulting in complete healing of that wound. Remarkably, no short- or long-term complications associated with the flap were observed. Three months after hospital discharge, the patient regained mobility, walking on 1 leg with the assistance of a 4-legged walker. CONCLUSION: The anchoring flap suture technique seems to be a reliable and effective treatment option, particularly in cases in which inadequate soft tissue precludes the use of traditional flap fixation using standard sutures.

Transfusion-Related acute lung injury (TRALI) caused by antibodies to HLA-DRB1* 07:01 and HLA-DQB1*02:02: A case report.

Transfusion-related acute lung injury (TRALI) is characterized by non-cardiogenic pulmonary edema and acute hypoxemia. There are few reports of HLA-II antibodies causing TRALI in China.

Dimethyl Fumarate Protects against Lipopolysaccharide- (LPS-) Induced Sepsis through Inhibition of NF-κB Pathway in Mice.

Sepsis is one of the most severe complications and causes of mortality in the clinic. It remains a great challenge with no effective treatment for clinicians worldwide. Inhibiting the release of proinflammatory cytokines during sepsis is considered as an important strategy for treating sepsis and improving survival. In the present study, we have observed the effect of dimethyl fumarate (DMF) on lipopolysaccharide- (LPS-) induced sepsis and investigated the possible mechanism. By screening a subset of the Johns Hopkins Drug Library, we identified DMF as a novel inhibitor of nitric oxide synthesis in LPS-stimulated RAW264.7 cells, suggesting that DMF could be a potential drug to treat sepsis. To further characterize the effect of DMF on LPS signaling, TNF-α, MCP-1, G-CMF, and IL-6 expression levels were determined by using cytokine array panels. In addition, an endotoxemia model with C57BL/6 mice was used to assess the in vivo efficacy of DMF on sepsis. The survival rate was assessed, and HE staining was performed to investigate histopathological damage to the organs. DMF was found to increase the survival of septic mice by 50% and attenuate organ damage, consistent with the reduction in IL-10, IL-6, and TNF-α (inflammatory cytokines) in serum. In vitro experiments revealed DMF's inhibitory effect on the phosphorylation of p65, IκB, and IKK, suggesting that the primary inhibitory effects of DMF can be attributed, at least in part, to the inhibition of phosphorylation of IκBα, IKK as well as nuclear factor-κB (NF-κB) upon LPS stimulation. The findings demonstrate that DMF dramatically inhibits NO and proinflammatory cytokine production in response to LPS and improves survival in septic mice, raising the possibility that DMF has the potential to be repurposed as a new treatment of sepsis.

Relationship between physical activity and individual mental health after traumatic events: a systematic review.

Background: Traumatic events can cause social tension, anxiety, panic and other psychological crises, and can even cause post-traumatic stress disorder (PTSD) and suicide. Physical activity has a good role in promoting mental health, and has a great application prospect in individual psychological intervention after traumatic events. However, no systematic review of the relationship between physical activity and individual mental health after traumatic events affecting many people has been published so far, which makes it impossible for people to understand the research status in this field from a holistic perspective.Objective: This review explores the relationship between physical activity and individual psychology, physiology, subjective quality of life and well-being after traumatic events, so as to provide some valuable clues or enlightenment for individual psychological intervention after traumatic events.Method: Relevant literature was searched in five databases, summarised, sorted and studied.Results: Thirty-three study papers were included in this review, the main study findings include: (1) Physical activity is positively correlated with individual mental resilience and subjective well-being after traumatic events, and negatively correlated with anxiety, depression, tension and PTSD. (2) Individuals with higher levels of physical activity have better mental health status after traumatic events than those who do not regularly engage in physical activity. (3) Physical activity can promote sleep quality, self-efficacy, subjective quality of life and various physiological functions of those experiencing traumatic events. (4) Physical activity (including exercise) is regarded as one of the preferred nursing measures to buffer against mental stress and maintain physical and mental health for those experiencing traumatic events.Conclusion: The level of physical activity is positively correlated with individual physical and mental health before and after traumatic events. Physical activity can be used as one of the effective measures to improve individual mental health after traumatic events.

Physical activity can be used as one of the important measures to improve mental health of those experiencing traumatic events.Regular physical activity can reduce the impact of traumatic events on mental health, both before and after the events.

A real-time computer-aided diagnosis method for hydatidiform mole recognition using deep neural network.

BACKGROUND AND OBJECTIVE: Hydatidiform mole (HM) is one of the most common gestational trophoblastic diseases with malignant potential. Histopathological examination is the primary method for diagnosing HM. However, due to the obscure and confusing pathology features of HM, significant observer variability exists among pathologists, leading to over- and misdiagnosis in clinical practice. Efficient feature extraction can significantly improve the accuracy and speed of the diagnostic process. Deep neural network (DNN) has been proven to have excellent feature extraction and segmentation capabilities, which is widely used in clinical practice for many other diseases. We constructed a deep learning-based CAD method to recognize HM hydrops lesions under the microscopic view in real-time. METHODS: To solve the challenge of lesion segmentation due to difficulties in extracting effective features from HM slide images, we proposed a hydrops lesion recognition module that employs DeepLabv3+ with our novel compound loss function and a stepwise training strategy to achieve great performance in recognizing hydrops lesions at both pixel and lesion level. Meanwhile, a Fourier transform-based image mosaic module and an edge extension module for image sequences were developed to make the recognition model more applicable to the case of moving slides in clinical practice. Such an approach also addresses the situation where the model has poor results for image edge recognition. RESULTS: We evaluated our method using widely adopted DNNs on an HM dataset and chose DeepLabv3+ with our compound loss function as the segmentation model. The comparison experiments show that the edge extension module is able to improve the model performance by at most 3.4% regarding pixel-level IoU and 9.0% regarding lesion-level IoU. As for the final result, our method is able to achieve a pixel-level IoU of 77.0%, a precision of 86.0%, and a lesion-level recall of 86.2% while having a response time of 82 ms per frame. Experiments show that our method is able to display the full microscopic view with accurately labeled HM hydrops lesions following the movement of slides in real-time. CONCLUSIONS: To the best of our knowledge, this is the first method to utilize deep neural networks in HM lesion recognition. This method provides a robust and accurate solution with powerful feature extraction and segmentation capabilities for auxiliary diagnosis of HM.

S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma.

BACKGROUND: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. METHODS: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. RESULTS: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. CONCLUSION: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.

Psychological challenges and related factors of ordinary residents after "7.20" heavy rainstorm disaster in Zhengzhou: a cross-sectional survey and study.

BACKGROUND: In 2021, a once-in-a-century heavy rainstorm suddenly attacked Zhengzhou, an important inland city in northern China. However, there have been no studies on the psychological health of disaster-stricken residents. This study is the first to comprehensively report on the mental health status and related factors of local ordinary residents after the heavy rainstorm. OBJECTIVE: The purpose of this study is to investigate the mental health status and related influencing factors of local ordinary residents after the flood disaster, and to provide reference for government departments to formulate disaster psychological intervention countermeasures based on evidence-driven strategies. METHODS: The snowball sampling technique was used in this study, and measurement tools of Rainstorm Exposure Questionnaire, Subjective Perception of Rainstorm, Post-Traumatic Stress Disorder Checklist-Civilian version (PCL-C), Depression, Anxiety and Stress Scale-21 (DAS-21) and Chinese version of Social Support Rating Scale (SSRS) were used to evaluate the rainstorm exposure, subjective perception of the rainstorm, psychological symptoms and social support of the disaster-stricken residents within a week after the rainstorm. Logistic regression analysis was used to examine the psychological status and related factors of local residents after the rainstorm disaster. RESULTS: A total of 469 valid samples were obtained in this study. All the subjects were in the disaster area and experienced the rainstorm personally, with normal intelligence. The statistical results showed that 25.37% people had experienced at least three rainstorm-related stresses, nearly 20.26% people had post-traumatic stress disorder (PTSD) symptoms, and 39.3%, 53.92% and 65.83% people had depression, anxiety and stress symptoms, respectively. Multivariable logistic regression analyses indicated that female (all p < 0.05), the divorced, agricultural workers/farmers (all p < 0.05), students (all p < 0.05), people experiencing at least three rainstorm-related stresses (p < 0.05 or p < 0.01), people with lower satisfaction at the social flood fighting measures (p < 0.05 or p < 0.01) and people with low social support (p < 0.05 or p < 0.01) were all independent risk factors for poor psychological health, and college education or above (p < 0.05 or p < 0.01), the lower degree of worrying about themselves (all p < 0.01), family members (all p < 0.01) and family property (all p < 0.01) were all related to higher psychological health among flood survivors after the disaster. CONCLUSIONS: Rainstorm could cause local residents to have various degrees of psychological symptoms. This study identified factors associated with the psychological health of disaster-stricken residents, which could be used to develop psychological interventions in improving psychological health of local residents.

Within-patient randomised clinical trial exploring the development of microskin implantation in the treatment of pressure ulcers.

Pressure injury often seriously affects the life quality of aged patients, especially the long-term bedridden casualties. Widely adopted by different disciplines, negative pressure suction has its role in pressure injury. Microskin implantation has been demonstrated powerful in increasing the expansion ratio of donor area-derived skin and accelerating wound healing by forming "skin islands". The study was designed to evaluate the efficacy and safety of additional use of bedside microskin implantation in the palliative care of pressure injury of aged patients who cannot tolerate surgical treatment as a supplement for standard negative pressure suction. An open-label within-patient RCT was conducted in aged patients with pressure injury. Sixteen patients were enrolled. After granulation tissues formed, half of a pressure injury was randomised to receive the negative pressure suction as the control group, and the other half exposed to additional bedside microskin implantation as the experimental group. Efficacy was evaluated within 1 month after treatment, and the primary endpoints included the wound healing rate and pressure ulcer scale for healing (PUSH) scores. The secondary outcomes included survival rate of implanted microskin, pain intensity assessment, satisfaction surveys from patients or their family, and pressure ulcer healing complications. Sixteen patients completed the study. After 14 days of operation, 5.63 ± 1.78 out of 10 pieces of implanted microskin survived and formed neonatal epithelium. The wound healing rates of the control group and the experimental group at 1 month were (26.17 ± 9.03%) and (35.95 ± 16.02%), respectively (P < .01). The mean PUSH score before the surgery was 12.38 ± 2.23. At 1 month after surgery, the mean difference of PUSH score from baseline was 2.13 ± 0.96 in the control group and 2.81 ± 0.83 in the experimental group (P < .01). The treatment of microskin implantation did not cause additional pain or complications to the patients. Accompanied by a better ulcer status, the majority of patients or their guardians have a high degree of acceptance towards the microskin implantation. Bedside microskin implantation could accelerate wound healing with lower PUSH scores. As a complementary palliative treatment, supplementary microskin implantation is effective and well tolerated.

Epigenetic modulation enhances immunotherapy for pancreatic ductal adenocarcinoma.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. PDAC has poor response to immunotherapy because of its unique tumour microenvironment (TME). In an attempt to stimulate immunologically silent pancreatic cancer, we investigated the role of epigenetic therapy in modulating the TME to improve immunogenicity. Methods: In vitro human PDAC cell lines MiaPaca2 and S2-013 were treated with 5µ m 3-Deazaneplanocin A (DZNep, an EZH2 inhibitor) and 5 µ m 5-Azacytidine (5-AZA, a DNMT1 inhibitor). In vivo orthotopic murine tumour models using both murine PAN02 cells and KPC cells inoculated in immunocompetent C56/BL7 mice were treated with anti-PD-L1 combined with DZNep and 5-AZA. Short hairpin knockdown (KD) of EZH2 and DNMT1 in PAN02 cells for the orthotopic murine tumour model was established to validate the drug treatment (DZNep and 5-AZA). qRT-PCR and microarray assays were performed for the evaluation of Th1-attracting chemokines and cancer-associated antigen induction. Results: Drug treatments induced significant upregulation of gene expressions of Th1-attracting chemokines, CXCL9 and CXCL10, and the cancer-testis antigens, NY-ESO-1, LAGE and SSX-4 (P < 0.05). In orthotopic tumour models, inoculation of PAN02 cells or KPC cells demonstrated significant tumour regression with corresponding increased apoptosis and infiltration of cytotoxic T lymphocytes in the combination treatment group. In the orthotopic Pan02-KD model, the anti-PD-L1 treatment also caused significant tumour regression. Conclusion: We demonstrate that immunotherapy for PDAC can be potentiated with epigenetic therapy by increasing cancer-associated antigen expression and increased T-cell trafficking across the immunosuppressive tumour microenvironment via upregulation of the repressed chemokines and increased apoptosis with subsequent tumour regression.

Overdrive pacing in the acute management of osimertinib-induced ventricular arrhythmias: A case report and literature review.

QT interval prolongation and ventricular arrhythmias (VAs) induced by osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, are life-threatening complications. However, no consensus has been achieved regarding their management. Overdrive pacing has been shown to be effective in shortening the QT interval and terminating torsade de pointes (TdP). Here, we report a case of osimertinib-induced QT prolongation accompanied by frequent VAs and TdP. Osimertinib was immediately discontinued after it was identified as the etiology for QT prolongation and VAs. A temporary pacemaker and overdrive pacing were used after other anti-arrhythmia treatments had failed and successfully shortened the QTc interval and terminated VAs. Repeated Holter monitoring at 1 week showed no remaining VAs or TdP, and the pacemaker was removed. Routine electrocardiography (ECG) surveillance was conducted afterward, and three- and 6-month follow-ups showed good recovery and normal ECG results. Vigilance is required for rare vital arrhythmias in patients taking osimertinib, and ECG surveillance should be conducted.

Improving the prognostic ability of PET/CT SUVmax to identify follicular lymphoma with early treatment failure.

Follicular lymphoma (FL) has a high degree of heterogeneity both clinically and molecularly. Early treatment failure (ETF), progression or relapse within 24 months of frontline immunochemotherapy is associated with a poor prognosis in FL. However, the clinical utility of ETF at diagnosis is limited. The maximum standardized uptake value (SUVmax) is a metabolic parameter for positron emission tomography/computed tomography (PET/CT); nevertheless, the relationship between SUVmax and ETF remains unclear. Thus, identifying early biomarkers that incorporate SUVmax and other clinical correlative variables could be helpful in identifying patients at high risk of ETF. A nomogram consisted of three independent variables, including SUVmax ≥ 12, beta-2 microglobulin > 3 mg/L, and Ki67 > 40%, was established to predict ETF in 127 patients with grade 1, 2, or 3a FL from the First Hospital of Jilin University (training cohort) and was validated using data from the Duke University Medical Center (validation cohort, n=95). The nomogram demonstrated prognostic accuracy in predicting ETF (sensitivity 70.8% and specificity 83.5% in the training cohort; sensitivity 84.2% and specificity 68.4% in the validation cohort). The patients were stratified into three groups: low-, intermediate-, and high-risk. In the training cohort, the corresponding 5-year progression-free survival (PFS) rates were 81.7%, 73.4%, and 34.9%, and the 5-year overall survival (OS) rates were 97.4%, 87.4%, and 62.3%, respectively. In the validation cohort, the 5-year PFS rates were 77.7%, 52.9%, and 34.8%, and the 5-year OS rates were 96.4%, 94.1%, and 73.7%, respectively. This was the first study to use a nomogram with SUVmax to predict ETF in FL to identify a subset of patients who might benefit from individualized targeted therapy.

Cross-sectional investigation and correlation analysis of psychology of college students returning to campus after COVID-19 lockdown lift.

Objective: To conduct a large cross-sectional survey of the mental health of college students during the recovery period of the COVID-19 epidemic. Methods: Symptom Checklist 90 (SCL-90) and COVID-19 questionnaire were used to investigate the overall mental health level and cognition of epidemic situation of college students in seven colleges and universities in Shaanxi Province. Results: (1) In the recovery period of COVID-19 epidemic, college students still had psychological and somatic symptoms such as obsessive-compulsive disorder, interpersonal sensitivity, anxiety, hostility, and poor appetite or insomnia; (2) female college students, science and engineering college students, freshmen and senior graduates, and some ethnic minority college students were all groups with psychological symptoms; (3) the psychological status of college students was related to their perception of COVID-19 epidemic, and the more knowledge about epidemic prevention and control, the more confident they were in overcoming the epidemic, and the milder the psychological symptoms. Conclusion: College students still have some mental health problems in the recovery period of COVID-19 epidemic, which should be paid attention to by education authorities and colleges and universities.

Short-term outcomes of neoadjuvant sintilimab with chemotherapy in stage III non-small cell lung cancer: a case series.

Background: Neoadjuvant chemoimmunotherapy seems to be a promising treatment option for stage III non-small cell lung cancer (NSCLC). Sintilimab, as a programmed death receptor-1 inhibitor, has exhibited a fine performance in treating NSCLC. However, the efficiency of sintilimab combined with chemotherapy for stage IIIA/IIIB NSCLC remains inconclusive. The purpose of this study was to share our experience on sintilimab in neoadjuvant chemoimmunotherapy for stage III NSCLC. Methods: This study retrospectively reviewed patients who received surgical resection following 1-3 cycles of neoadjuvant sintilimab (200 mg) with chemotherapy for stage III NSCLC between June 2020 and March 2022 in our center. Patients characteristics, surgical factors, surgery-related complications 30 days postoperatively, and treatment-related adverse events (TRAEs) before surgery were recorded through reviewing medical record data and telephone follow-up. Results: A total of eight patients were enrolled, including six cases of squamous cell carcinoma and two cases of adenocarcinoma. All of the patients received 1-3 cycles of neoadjuvant therapy. There were no treatment-related surgical delays. All patients underwent lobectomy, among which two underwent sleeve lobectomy and one received bronchoplasty. Five patients underwent open thoracotomy. Fibrosis of the primary tumor and lymph nodes was observed in all the cases. There were no surgery-related complications > grade 2 at 30 days postoperatively. According to the radiographic findings, one patient had stable disease and all of the others achieved a partial response. The median of maximum standardized uptake value change from baseline was a 52.75% reduction (range, 37.2-68.8%). Five patients achieved a major pathological response. R0 resection was achieved in all eight cases. One grade 4 event was observed. Neutropenia was the most common TRAE > grade 2 (3/8). There were no cases of treatment discontinuation or dose reduction due to TRAEs. Conclusions: The current study found that neoadjuvant sintilimab plus chemotherapy bring a high rate of major pathological response and acceptable TRAEs. Even though it increased the difficulties of surgery, there is still no evidence suggesting that it will brings additional surgical death. We believe that neoadjuvant sintilimab plus chemotherapy might be feasible for stage III NSCLC.

Chidamide Maintenance Therapy Following Induction Therapy in Patients With Peripheral T-Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation: Case Series From China.

Objective: To assess the potential benefit of chidamide maintenance therapy after induction treatment in peripheral T-cell lymphoma (PTCL). Materials and Methods: The clinical data of 48 transplantation-ineligible patients with different PTCL subtypes who received continuous chidamide treatment after first-line therapy were collected. Progression-free survival (PFS), overall survival (OS), and safety were analyzed. Results: In total, 68.8% of patients were male (33/48), the median age was 59.5 years (22~80). The pathological subtypes were angioimmunoblastic T-cell lymphoma (AITL, 43.8%), anaplastic large cell lymphoma (ALCL, 16.6%), PTCL-not otherwise specified (NOS, 25%), NK/T-cell lymphoma (NKT, 14.6%). 35.4% (7/48) patients had intermediate or high risk (IPI=3~5). 20 patients (41.7%) received chidamide as a maintenance treatment after achieving a complete response (CR). 57.1% (16/28) exhibited a better response after chidamide (9 cases partial response [PR] to CR, 7 from stable disease [SD] to PR). The CR and overall response rate (ORR) were 60.4% and 93.8%, respectively. In addition, 21/21 AITL, 10/12 PTCL-NOS, and 8/8 ALCL, 6/7 NK/T exhibited CR/PR as the best response during the follow-up period. Meanwhile, the CR and ORR did not differ by age (<60 vs ≥60: 50.0% vs 70.8%, P = 0.091; and 91.7% vs 95.8%, P = 0.551). The median follow-up period was 12.8 months (3.0-66.6), 14 patients developed PD (29.2%), 10 of them died of lymphoma (20.8%). Totally, the 40 cases achieved CR/PR from 1st line regimen got better PFS as well as OS than the rest 8 cases (the 1-year PFS was 80.8% vs 46.9% and the 2-year PFS was 71.9% vs 46.9%, P=0.012. the 1-year OS was 89.9% vs 72.6% and the 2-year OS was 85.9% vs 48.6%, P=0.032). No patients discontinued treatment because of adverse events. The most common toxicities were neutropenia (75.0%), anemia (79.2%), thrombocytopenia (58.3%), and anorexia (45.8%), and fatigue (43.8%). Conclusion: Chidamide maintenance therapy led to improvements of PFS and OS with a manageable safety profile in patients with PTCL. Further randomized studies are required to examine the role of chidamide maintenance therapy in PTCL.

Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk.

Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular P. gingivalis and infected host cells via dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of P. gingivalis livk and livh genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by P. gingivalis, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury via livh/livk. To verify this hypothesis, we constructed P. gingivalis livh/livk-deficient strains (Δlivk, Δlivh) and established a high-fat diet (HFD)-fed murine model infected with P. gingivalis. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and in vivo colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that P. gingivalis infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, livh deletion had no effect on bacterial growth, EPS production, invasion efficiency, and in vivo colonization, whereas the Δlivk strain showed a slight decrease in invasion efficiency and in vivo colonization. More importantly, however, both the Δlivk and Δlivh strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that P. gingivalis possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system.

Second malignant neoplasms in lymphomas, secondary lymphomas and lymphomas in metabolic disorders/diseases.

With inconsistent findings, evidence has been obtained in recent years that metabolic disorders are closely associated with the development of lymphomas. Studies and multiple analyses have been published also indicating that some solid tumor survivors develop a secondary lymphoma, whereas some lymphoma survivors subsequently develop a second malignant neoplasm (SMN), particularly solid tumors. An interaction between the multiple etiologic factors such as genetic factors and late effects of cancer therapy may play an important role contributing to the carcinogenesis in patients with metabolic diseases or with a primary cancer. In this review, we summarize the current knowledge of the multiple etiologic factors for lymphomagenesis, focusing on the SMN in lymphoma, secondary lymphomas in primary cancers, and the lymphomas associated to metabolic disorders/diseases, which have been received less attention previously. Further, we also review the data of coexistence of lymphomas and hepatocellular carcinoma (HCC) in patients with infection of hepatitis C virus and hepatitis B virus.

Nilotinib related acute myocardial infarction with nonobstructive coronary arteries: a case report and literature review.

BACKGROUND: Myocardial Ischemia with No Obstructive Coronary Artery Disease (MINOCA) is a common cause of type 2 acute myocardial infarction (AMI) which requires careful differential diagnosis. Coronary artery spasm (CAS) syndrome is one etiology that can lead to MINOCA. Nilotinib, a targeted treatment for chronic myeloid leukemia (CML), has been reported to be related with increased risk of adverse vascular events. CASE PRESENTATION: A 67-year-old male patient was admitted to hospital with acute chest pain. He had a past medical history of CML and a history of treatment with nilotinib for 12 months. Coronary angiography (CAG) showed no significant stenosis. Since the onset of angina was generally in the early morning, and ECG and echocardiography suggested right coronary artery (RCA) disease, an ergonovine provocation test was performed to confirm the diagnosis of CAS. After intracoronary administration of ergonovine, middle and distal RCA showed over 90% vasoconstriction. Nilotinib related MINOCA, CAS and CML were diagnosed. Lifestyle changes (cessation of smoking), anti-spasmodics, statin treatment and adjustment of the nilotinib dose (from 200 mg bid, to 150 mg bid) were recommended for this patient. Six-month's follow-up showed good recovery with no onsets of angina. CONCLUSIONS: Physicians should be vigilant to adverse vascular events when treating patients who have been prescribed nilotinib. It is suggested that in patients with MINOCA who have a history of treatment with nilotinib, CAS-induced MINOCA should be included in the differential diagnosis. Further studies are needed to clarify the mechanism and to find better management.

Efficacy and Safety of Lenalidomide Monotherapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma: Systematic Review and Meta-Analysis.

INTRODUCTION: Several maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes. RESULTS: We included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months. CONCLUSION: This study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.

Aberrant FGFR4 signaling worsens nonalcoholic steatohepatitis in FGF21KO mice.

Background: Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease (NAFLD) and a potential precursor of hepatocellular carcinoma (HCC). In our previous studies, we found that endocrine fibroblast growth factor 21 (FGF21) played a key role in preventing the development of NASH, however, the FGF15/19 mediated-FGFR4 signaling worsened NASH and even contributed to the NASH-HCC transition. The aim of this study is to determine whether FGF15/FGFR4 signaling could alleviate or aggravate NASH in the FGF21KO mice. Methods: NASH models were established in FGF21KO mice fed with high fat methionine-choline deficient (HFMCD) diet to investigate FGF15/FGFR4 signaling during early stage NASH and advanced stage NASH. Human hepatocytes, HepG2 and Hep3B cells, were cultured with human enterocytes Caco-2 cells to mimic gut-liver circulation to investigate the potential mechanism of NASH development. Results: Significant increase of FGF15 production was found in the liver of the NASH-FGF21KO mice, however the increased FGF15 protein was unable to alleviate hepatic lipid accumulation. In contrast, up-regulated FGF15/19/FGFR4 signaling was found in the FGF21KO mice with increased NASH severity, as evident by hepatocyte injury/repair, fibrosis and potential malignant events. In in vitro studies, blockage of FGFR4 by BLU9931 treatment attenuated the lipid accumulation, up-regulated cyclin D1, and epithelial-mesenchymal transition (EMT) in the hepatocytes. Conclusion: The increased FGF15 in NASH-FGF21KO mice could not substitute for FGF21 to compensate its lipid metabolic benefits thereby to prevent NASH development. Up-regulated FGFR4 signaling in NASH-FGF21KO mice coupled to proliferation and EMT events which were widely accepted to be associated with carcinogenic transformation.