Construction of an early differentiation diagnosis model for patients with severe fever with thrombocytopenia syndrome and hemorrhagic fever with renal syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high mortality rate. Differentiating between SFTS and hemorrhagic fever with renal syndrome (HFRS) is difficult and inefficient. Retrospective analysis of the medical records of individuals with SFTS and HFRS was performed. Clinical and laboratory data were compared, and a diagnostic model was developed based on multivariate logistic regression analyzes. Receiver operating characteristic curve analysis was used to evaluate the diagnostic model. Among the 189 patients, 113 with SFTS and 76 with HFRS were enrolled. Univariate analysis revealed that more than 20 variables were significantly associated with SFTS. Multivariate logistic regression analysis revealed that gender, especially female gender (odds ratio [OR]: 4.299; 95% confidence interval [CI]: 1.163-15.887; p = 0.029), age ≥65 years (OR: 16.386; 95% CI: 3.043-88.245; p = 0.001), neurological symptoms (OR: 12.312; 95% CI: 1.638-92.530; p = 0.015), leukopenia (<4.0 × 109/L) (OR: 17.355; 95% CI: 3.920-76.839; p < 0.001), and normal Cr (OR: 97.678; 95% CI: 15.483-616.226; p < 0.001) were significantly associated with SFTS but not with HFRS. The area under the curve of the differential diagnostic model was 0.960 (95% CI: 0.936-0.984), which was significantly better than that of each single factor. In addition, the model exhibited very excellent sensitivity and specificity (92.9% and 85.5%, respectively). In cases where HFRS and SFTS are endemic, a diagnostic model based on five parameters, such as gender, age ≥65 years, neurological symptoms, leukopenia and normal Cr, will facilitate the differential diagnosis of SFTS and HFRS in medical institutions, especially in primary care settings.

Trends of type 2 diabetes with pulmonary tuberculosis patients,2013-2022, and changes after the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: To describe the trends of Type 2 Diabetes with Pulmonary Tuberculosis (T2DM-TB) patients from 2013 to 2022 and to investigate the impact of COVID-19 lockdown on glycemic control and associated factors in T2DM-TB. METHODS: In this population-based study of the First Affiliated Yijishan Hospital of Wannan Medical College in China, we described the 10-year trends of patients diagnosed with T2DM-TB. We included patients diagnosed with TB, T2DM-TB and T2DM-TB patients for comparative analysis, aged 15 years or older. Data were missing, and both multidrug-resistant (MDR) TB patients and non-T2DM patients were excluded from our study. RESULTS: We pooled Type 2 Diabetes (T2DM) and Tuberculosis (TB) data from The First Affiliated Yijishan Hospital of Wannan Medical College in China, gathered between January 1, 2013, and December 31, 2022. The data included 14,227 T2DM patients, 6130 TB patients, and 982 T2DM-TB patients. During the past 10 years, the number of inpatients with TB decreased, while the number of patients with T2DM and T2DM-TB increased year by year. To rule out any influence factors, we analyzed the ratio of the three groups. The ratio of TB/T2DM decreased year by year (p < 0.05), while the ratio of TB-T2DM/TB increasing year by year (p = 0.008). During the COVID-19 epidemic period, there was no significant change in the ratio of TB-T2DM/T2DM (p = 0.156). There was no significant change in the proportion of male patients with TB and TB-T2DM (p = 0.325; p = 0.190), but the proportion of male patients with T2DM showed an increasing trend (p < 0.001). The average age of TB patients over the past 10 years was 54.5 ± 18.4 years and showed an increasing trend year by year (p < 0.001). However, there was no significant change in the age of T2DM or TB-T2DM patients (p = 0.064; p = 0.241). Patients data for the first (2013-2017) and the last (2018-2022) five years were compared. We found that the number of T2DM and TB-T2DM in the last five years was significantly higher than in the first five years, but the number of TB was significantly lower than in the first five years. There is a significant statistical difference in the proportion of TB/T2DM and TB-T2DM/TB, which is similar to the previous results. The average age (56.0 ± 17.6 years) of TB patients in the last five years is significantly higher than in the first five years (53.1 ± 18.9) (p < 0.001). The number of male patients with T2DM in the last five years is higher than that in the first five years, with significant difference (p < 0.001). CONCLUSION: The trends of T2DM-TB among hospitalized TB patients have increased significantly over the past 10 years, which may be related to the increase in the number of T2DM cases. The COVID-19 pandemic has been effective in controlling the transmission of TB, but it has been detrimental to the control of T2DM. Male patients with T2DM and elderly TB patients are the key populations for future prevention and control efforts.

E3 ligase TRIM28 promotes anti-PD-1 resistance in non-small cell lung cancer by enhancing the recruitment of myeloid-derived suppressor cells.

BACKGROUND: Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). METHODS: We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the KrasLSL-G12D/+; Tp53fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. RESULTS: Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. CONCLUSION: The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.

Metabolomics and Transcriptomics Analyses Reveals the Molecular Regulatory Mechanisms of Walnut (Juglans regia L.) Embryos in Response to Shade Treatment.

The walnut is an important nut that has numerous uses worldwide. However, due to dwarf and close plantation methods as well as continuous cloudy or rainy days that occur during periods of walnut oil accumulation, the walnut fruit exhibits varying degrees of stress under low-light conditions. However, the effects of shade on metabolites and genes in walnut embryos remain unclear in the literature. The purpose of this study is to investigate the lipid biosynthesis process that occurs in walnut embryos under shade treatment via the use of metabolomics and transcriptomics analyses. The results indicate that the oil content decreases significantly under shaded conditions, while the protein content increases significantly. The expression levels of fatty acid desaturase 2 (FAD2) and stearoyl-ACP-desaturase (SAD) involved in the lipid biosynthesis mechanism were significantly reduced in the shaded group, which resulted in reductions in oleic (C18:1), linoleic (C18:2), and α-linolenic (C18:3) acids. The reduced oil content was consistent with the downregulation of genes associated with the lipid biosynthesis mechanism. In the amino acid biosynthesis process, the upregulated cysteine synthase (cscK) and anthranilate synthase beta subunit 2 (trpG) genes promoted the accumulation of L-aspartic acid and L-citrulline. The increase in protein content was consistent with the upregulation of genes related to amino acid biosynthesis. Thus, our study provides new insights into the regulatory mechanisms of shade underlying overall walnut fruit quality.

Metabolomics and Transcriptomics Provide Insights into Lipid Biosynthesis in the Embryos of Walnut (Juglans regia L.).

Walnut (Juglans regia L.) is an important woody oilseed tree species due to its commercial value. However, the regulation mechanism of walnut oil accumulation is still poorly understood, which restricted the breeding and genetic improvement of high-quality oil-bearing walnuts. In order to explore the metabolic mechanism that regulates the synthesis of walnut oil, we used transcriptome sequencing technology and metabolome technology to comprehensively analyze the key genes and metabolites involved in oil synthesis of the walnut embryo at 60, 90, and 120 days after pollination (DAP). The results showed that the oil and protein contents increased gradually during fruit development, comprising 69.61% and 18.32% of the fruit, respectively, during ripening. Conversely, the contents of soluble sugar and starch decreased gradually during fruit development, comprising 2.14% and 0.84%, respectively, during ripening. Transcriptome sequencing generated 40,631 unigenes across 9 cDNA libraries. We identified 51 and 25 candidate unigenes related to the biosynthesis of fatty acid and the biosynthesis of triacylglycerol (TAG), respectively. The expression levels of the genes encoding Acetyl-CoA carboxylase (ACCase), long-chain acyl-CoA synthetases (LACS), 3-oxoacyl-ACP synthase II (KASII), and glycerol-3-phosphate acyl transfer (GPAT) were upregulated at 60 DAP relative to the levels at 90 and 120 DAP, while the stearoyl-ACP-desaturase (SAD) and fatty acid desaturase 2 (FAD2) genes were highly abundantly expressed during all walnut developmental periods. We found that ABSCISIC ACID INSENSEITIVE3 (ABI3), WRINKLEDl (WRI1), LEAFY COTYLEDON1 (LEC1), and FUSCA3 (FUS3) may be key transcription factors involved in lipid synthesis. Additionally, the metabolomics analysis detected 706 metabolites derived from 18 samples, among which, 4 are implicated in the TAG synthesis, 2 in the glycolysis pathway, and 5 in the tricarboxylic acid cycle (TCA cycle) pathway. The combined analysis of the related genes and metabolites in TAG synthesis showed that phospholipid:diacylglycerol acyltransferase (PDAT) genes were highly abundantly expressed across walnut fruit developmental periods, and their downstream metabolite TAG gradually accumulated with the progression of fruit development. The FAD2 gene showed consistently higher expression during fruit development, and its downstream metabolites 18:2-PC and 18:3-PC gradually accumulated. The ACCase, LACS, SAD, FAD2, and PDAT genes may be crucial genes required for walnut oil synthesis. Our data will enrich public databases and provide new insights into functional genes related to lipid metabolism in walnut.

Ultrasound activatable microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy.

Chemodynamic therapy (CDT) employs Fenton catalysts to kill bacteria by converting hydrogen peroxide (H2O2) into toxic hydroxyl radical (•OH). Among them, Fenton-type metal peroxide nanoparticles fascinate nanomaterials with intriguing physiochemical properties, but research on this antibacterial agent is still in its infancy. Herein, a distinct CuO2/TiO2 heterostructure constituted of ultrasmall copper peroxide (CuO2) nanoclusters and sonosensitized ultrathin oxygen vacancy-rich porous titanium oxide (OV-TiO2) nanosheets was developed and was incorporated into microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy. Engineering CuO2 nanoclusters on the surface of TiO2 nanosheets not only endows the Fenton catalytic activity for sono-chemodynamic therapy (SCDT), but also improves the sonodynamic and sonothermal performance of TiO2 by narrowing the bandgap of TiO2 and suppressing the recombination of electron-hole pairs. The high efficacy of this CuO2/TiO2 integrated microneedle (CTMN) patch was systematically demonstrated both in vitro and in vivo with the eliminating rate >99.9999% against multidrug resistant (MDR) pathogens in 5 min as well as accelerated wound tissue healing. This work highlights a promisingly new and efficient strategy for the development of sonosensitive and chemoreactive nanomedicine for non-antibiotic therapies. STATEMENT OF SIGNIFICANCE: Feton-type metal peroxides, a novel nanomaterial with self-supplied oxygen and hydrogen peroxide, can achieve effective antimicrobial activity in vitro. However, there is a lack of effective nanomaterial delivery systems and suitable means for in vivo activation/enhancement of antimicrobial activity during bacterial infected skin wound treatment. In this study, we designed and prepared efficient ultrasound activable microneedles that effectively addressed the deficiencies mentioned above and established a new paradigm for efficient utilization of metal peroxide nanomaterials and ultrasound based strategies. Noticeably, copper peroxide nanoclusters/oxygen vacancy-rich porous titanium oxide nanosheets (CuO2/TiO2) integrated microneedle (CTMN) patch combines advantages of both sono-chemodynamic and sonothermal antibacterial therapy, achieving one of the most instant and effective antibacterial efficacy (>99.9999% in 5 min) in vivo reported till now.

Pancreatic injury is associated with poor prognosis in severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. Previous studies have mainly focused on the epidemiological and clinical characteristics of patients with SFTS, while pancreatic injury has received little attention. The purpose of this study is to investigate the effect of pancreatic injury on the prognosis of patients with SFTS. A total of 156 SFTS patients were included in the analysis from April 2016 to April 2022. Multivariable logistic regression analysis showed that pancreatic injury (OR=3.754, 95% CI 1.361-79.036, P=0.024) and neurological symptoms (OR=18.648, 95% CI 4.921-70.668, P<0.001) were independent risk factors for patient death. The receiver operating characteristic (ROC) curve indicated that serum pancreatic enzymes (PEs) were predictive of progression to death in SFTS patients. The area under the curve (AUC) for amylase (AMY) was 0.711, with an optimal cut-off value of 95.5 (U/L), sensitivity of 96.4%, and specificity of 35.9%. Lipase (LIP) had an AUC of 0.754, an optimal cut-off value of 354.75 (U/L), a sensitivity of 75%, and a specificity of 67.2%. Thus, pancreatic injury is associated with a poor prognosis of SFTS and can be used as an important reference for SFTS disease determination and prognostic assessment.

Machine Learning Guided Discovery of Superoxide Dismutase Nanozymes for Androgenetic Alopecia.

Androgenetic alopecia (AGA) is a common form of hair loss, which is mainly caused by oxidative stress induced dysregulation of hair follicles (HF). Herein, a highly efficient manganese thiophosphite (MnPS3) based superoxide dismutase (SOD) mimic was discovered using machine learning (ML) tools. Remarkably, the IC50 of MnPS3 is 3.61 µg·mL-1, up to 12-fold lower than most reported SOD-like nanozymes. Moreover, a MnPS3 microneedle patch (MnMNP) was constructed to treat AGA that could diffuse into the deep skin where HFs exist and remove excess reactive oxygen species. Compared with the widely used minoxidil, MnMNP exhibits higher ability on hair regeneration, even at a reduced frequency of application. This study not only provides a general guideline for the accelerated discovery of SOD-like nanozymes by ML techniques, but also shows a great potential as a next generation approach for rational design of nanozymes.

E3 ligase TRIM15 facilitates non-small cell lung cancer progression through mediating Keap1-Nrf2 signaling pathway.

BACKGROUND: Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. METHODS: TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. RESULTS: Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. CONCLUSIONS: Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract.

Silver Peroxide Nanoparticles for Combined Antibacterial Sonodynamic and Photothermal Therapy.

Metal peroxide nanoparticles designed to elevate the oxidative stress are considered a promising nanotherapeutics in biomedical applications, including chemotherapy, photodynamic therapy, and bacterial disinfection. However, their lack of specificity towards the therapeutic target can cause toxic side effects to healthy tissues. Here, silver peroxide nanoparticles (Ag2 O2 NPs) capable of controlled reactive oxygen species (ROS) release are synthesized. The release of bactericidal Ag+ ions and ROS is strictly regulated by external stimuli of ultrasound (US) and near-infrared (NIR) light. In vitro and in vivo investigations show that the Ag2 O2 NPs present enhanced antibacterial and antibiofilm capabilities with a killing efficiency >99.9999% in 10 min, significantly accelerate multi-drug resistant Staphylococcus aureus infected skin wound closure with excellent cytocompatibility and hemocompatibility. This work not only provides the first paradigm for fabricating silver peroxide nanoparticle but also introduces a highly efficient noninvasive and safe therapeutic modality for combating bacterial infectious diseases.

Pomegranate-Like CuO2@SiO2 Nanospheres as H2O2 Self-Supplying and Robust Oxygen Generators for Enhanced Antibacterial Activity.

Reactive oxygen species (ROS)-induced nanosystems represent one of the most essential, efficient, and encouraging nanobactericides for eliminating bacterial infection concerning the increasing resistance threats of existing antibiotics. Among them, Fenton-type metal peroxide nanoparticles are exciting nanomaterials with intriguing physiochemical properties, yet the study of this antimicrobial agent is still in its infancy. Herein, a robust pH-responsive Fenton nanosystem is constructed by the assembly of copper peroxide nanodots in pomegranate-like mesoporous silica nanoshells (CuO2@SiO2) that are capable of self-supplying H2O2 and sustainably generating O2. The enhanced antimicrobial performance is attributed to the pH responsiveness and excellent Fenton catalytic activity through either the Cu2+-catalyzed conversion of H2O2 to detrimental ROS under acid treatment or in situ O2 evolution in neutral media. Moreover, in vitro and in vivo investigations demonstrate that this nanocomposite can exhibit boosted antimicrobial capabilities and can significantly accelerate skin wound closure, while retaining outstanding cytocompatibility and hemocompatibility. Given its excellent physicochemical and antimicrobial properties, the broad application of this nanocomposite in bacteria-associated wound management is anticipated.

Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression.

BACKGROUND: Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. METHODS: Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. RESULTS: We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1ß. CONCLUSIONS: Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1ß secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.

Aspirin enhances the clinical efficacy of anti-tuberculosis therapy in pulmonary tuberculosis in patients with type 2 diabetes mellitus.

Background: Tuberculosis in patients with diabetes mellitus is characterised by rapid disease progression, poor treatment efficacy, poor prognosis and poses a new challenge in tuberculosis treatment and control.Methods: Patients with pulmonary TB and type 2 DM were recruited at Yijishan Hospital of Wannan Medical College. A total of 348 patients were randomly assigned to two groups. The aspirin group (aspirin + TB/DM) included 174 patients who received anti-TB therapy and enteric-coated aspirin tablets (100 mg/tablet). The control group (placebo + TB/DM) included 174 patients who received anti-TB therapy and enteric-coated placebo tablets (an identical tablet containing no drug). Eighty-two patients in the aspirin group and 86 in the control group completed the trial and were included in the analysis. Clinical characteristics, laboratory test results, imaging data and side effects of aspirin were monitored.Results: Aspirin treatment affect certain signs and symptoms. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were lower in the aspirin group than in the control group after treatment (Both p = .000). The sputum-negative conversion rate was 86.7% in the aspirin group, significantly higher than in the control group (53.8%) (p = .031). After two months of treatment, the differences in the number of cases with cavities, the number of cavities, and maximum diameter of cavities in the aspirin group were statistically significant (p = .003, p = .023 and p = .015 respectively).Conclusion: Our findings suggest that aspirin may improve treatment in patients with pulmonary TB and type 2 DM.

Comparison of the clinicopathological features and prognoses of patients with schistosomal and nonschistosomal colorectal cancer.

Patients with schistosomal colorectal cancer (CRC) and nonschistosomal CRC have different clinicopathological features, laboratory test results and survival rates. Long-term infection with schistosomiasis in patients with CRC may affect the pathogenesis and subsequently change the mechanisms of CRC in these patients, resulting in changes in the survival rates of patients with schistosomal and nonschistosomal CRC. In China, the most common type of schistosomiasis is S. japonicum. The present study aimed to investigate the clinicopathological features and prognostic factors of schistosomal and nonschistosomal CRC. A total of 253 patients with schistosomal CRC and 2,885 patients with nonschistosomal CRC were analyzed and their symptoms, clinicopathological features and laboratory test results were retrospectively evaluated. Patients with CRC in the present study underwent radical resection at The First Affiliated Yijishan Hospital of Wannan Medical College between January 2012 and December 2018. A total of 3,138 patients with CRC were enrolled, 253 of whom were patients with schistosomal CRC. Patients were followed-up to examine differences in the 5-year survival rates between patients with schistosomal and nonschistosomal CRC to determine whether schistosomiasis impacted the prognosis of CRC. There were significant differences in age, sex, fecal occult blood positive, pathological T stage, and CA19-9, WBC, RBC and PLT levels between patients with schistosomal CRC and nonschistosomal CRC. For residents in areas with higher levels of schistosomiasis infections, especially middle-aged and elderly males, serum tumor markers and digestive tract endoscopy should be regularly evaluated to detect the presence of digestive tract tumors as early as possible.

Clinical analysis of patients with acute pancreatitis complicated with hemorrhagic fever with renal syndrome and acute biliary pancreatitis.

Acute pancreatitis (AP) is a rare complication of hemorrhagic fever with renal syndrome (HFRS), and is difficult to diagnose. In this study, we retrospectively analyzed the clinical characteristics of 7 cases of HFRS complicated with AP and 105 cases of acute biliary pancreatitis (ABP).Medical records of 83 hospitalized patients with HFRS and 105 hospitalized patients with ABP in the affiliated Yijishan Hospital of Wannan Medical College were reviewed. The comparative analysis of patients between the 2 groups was conducted in terms of sex, age, duration of hospital stay, fever, hemorrhage, proteinuria, oliguria, laboratory results, radiologic examinations, and prognosis.A total of 83 patients were diagnosed with HFRS during study period. Only 8.43% (7/83) of the total HFRS patients were diagnosed with AP. The differences in the gender, age, and duration of hospital stay between the 2 investigated groups of patients were not statistically significant. The major symptoms for all 7 patients with HFRS complicated with AP and 105 patients with ABP were fever and upper abdominal pain. During the disease course of HFRS complicated with AP, 6 patients experienced hemorrhaging, and 7 patients underwent an oliguric stage, but none of the ABP patients experienced hemorrhaging and oliguria. Among the laboratory results of all patients, the differences in alanine aminotransferase and glycemia were not statistically significant. The other laboratory results (leucocyte count, platelet count, amylase, lipase, total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, prothrombin time, activated partial thromboplastin time, and serum calcium level) were significantly different during hospitalization. All 7 patients with HFRS complicated with AP received conservative medical treatment and hemodialysis. In the patients with ABP, 21 patients were discharged from the hospital after conservative treatment, 53 patients were treated by endoscopic invasive treatment after stabilization, and 31 patients were treated by surgery after stabilization.AP is not a frequent complication in patients with HFRS. There are differences in clinical manifestations and laboratory findings between the HFRS complicated with AP group and the ABP group; these differences may help in the differential diagnosis and treatment of these 2 types of pancreatitis.

An TRIM59-CDK6 axis regulates growth and metastasis of lung cancer.

Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up-regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular-signal regulated protein kinase (ERK) signalling pathway and epithelial-to-mesenchymal transition (EMT)-markers, as validated by loss-of-function studies. In-depth bioinformatics analysis showed that there is preliminary evidence of co-expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up-regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss- and gain-of-function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway.

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.