Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla _IMP gene harbored in the strain was most similar to bla _IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.
Infant, Newborn ; Child ; Humans ; Female ; Enterobacteriaceae Infections/microbiology* ; Enterobacteriaceae/genetics* ; Anti-Bacterial Agents/therapeutic use* ; Plasmids

OBJECTIVE: To investigate the clinicopathological features and prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2 -) breast cancer. METHODS: In the study, 3 035 consecutive breast cancer patients diagnosed in Breast Disease Center, Peking University First Hospital from January 2008 to December 2017 were collected. The prognostic signi-ficance of important pathological factors in HR +/HER2 - patients with complete clinicopathological information was analyzed. RESULTS: Within the 1 920 (63.26%) cases of HR +/HER2 - breast cancer, there were 1 624 cases with complete clinicopathological data, of which, 124 cases (7.64%) recurred and/or metastasized and 63 cases died of the disease, and the 5-year overall survival (OS) rate and disease-free survival (DFS) rate was 93.0% and 92.6% respectively. The stage of pT1-2 was 92.80%, while pN0 was 69.03%. 89.66% cases belonged to histologically non-specific type and 30.11%, 55.60%, 14.29% were credited to Grade 1, 2 and 3 respectively. The distribution of ER negative, low or high expression groups were 1.60%, 2.09% and 96.31%, while PR were 6.83%, 10.47%, 82.70%, respectively. The group of Ki67 index < 10% was 19.52%, ≥10% & < 20% for 32.02%, ≥20% for 48.46%. Survival analysis showed that cases with pT1 stage had lower risk of recurrence than those with pT3, while cases with pT2 and pT3 had shorter DFS than those with pT1, with higher risk of recurrence and metastasis. Analysis proved that both pN stage and histological grade were negatively correlated with DFS. The cases with pN0, pN1 and pN2 were lower risk of recurrence than those with pN3, while cases with Grade 1 and 2 had lower risk of recurrence than cases with Grade 3. And the group of Ki67 index ≥20% showed higher risk of recurrence and metastasis. The prognostic significance of ER expression in HR+/HER2- breast cancer was not significant. However, the negative/low PR expression groups showed higher risk of recurrence and metastasis, of which PR < 10% group had shortest DFS and OS, followed by 10%-60% group and then > 60% group. The most common site of metastasis was bone (55 cases, 44.35%), while cases with liver metastasis (30 cases, 24.20%) had the worst outcome. CONCLUSION Our study revealed that pT, pN, Grade, HR expression level and Ki67 index were important prognostic factors for HR +/HER2 - breast cancer, although there are variables in prognostic value. Factors of pN and Grade showed independent prognostic significance. PR expression level had prognostic significance for the risk of recurrence and metastasis. The stratified level of PR expression (< 10%, 10%-60%, >60%) had independent prognostic value, showing successively longer DFS and OS, lower risk of recurrence. PR>60% group had the longest DFS and OS as well as the lowest risk of recurrence.
Breast Neoplasms ; Disease-Free Survival ; Female ; Humans ; Ki-67 Antigen/metabolism* ; Prognosis ; Receptor, ErbB-2/metabolism* ; Receptors, Progesterone/analysis* ; Triple Negative Breast Neoplasms/metabolism*

Axilla/pathology* ; Breast Neoplasms/surgery* ; China ; Humans ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Mastectomy ; Neoplasm Staging ; Sentinel Lymph Node Biopsy

BACKGROUND: Minimal change nephropathy (MCD) is a common pathological type of nephrotic syndrome and is often associated with acute kidney injury (AKI). This study aimed to investigate the clinical characteristics and related factors of AKI in patients with MCD and nephrotic syndrome. METHODS: Patients from Chinese People's Liberation Army General Hospital who were diagnosed with pathological renal MCD with clinical manifestations of nephrotic syndrome were included from January 1, 2013 to December 31, 2017. Patients diagnosed with membranous nephropathy (MN) by renal biopsy from January 1, 2013 to December 31, 2017 are included as a control population. We retrospectively analyzed the clinical and pathological characteristics of patients as well as the percentages and clinical characteristics of AKI in different age groups. We assessed the correlation of pathological characteristics with serum creatinine using multivariate linear regression analysis. RESULTS: A total of 367 patients with MCD were included in the analysis, with a sex ratio of 1.46: 1 (male: female) and an age range of 6 to 77 years. Among all the patients, 109 developed AKI (29.7%), and of these patients, 85 were male (78.0%). In the 586 patients with MN, 27 (4.6%) patients developed AKI. The percentage of AKI in MCD patients was significantly higher than that in MN patients (χ2 = 41.063, P < 0.001). The percentage of AKI increased with age in the MCD patients. The percentage of AKI in patients aged 50 years or older was 52.9% (46/87), which was significantly higher than that [22.5% (63/280)] in patients under 50 years (χ2 = 6.347, P = 0.013). We observed statistically significant differences in age (43 [27, 59] years vs. 28 [20, 44] years, Z = 5.487, P < 0.001), male (78.0% vs. 51.4%, χ2 = 22.470, P < 0.001), serum albumin (19.9 ± 6.1 g/L vs. 21.5 ± 5.7 g/L, t = 2.376, P = 0.018), serum creatinine (129.5 [105.7, 171.1] μmol/L vs. 69.7 [57.7, 81.9] μmol/L, Z = 14.190, P < 0.001), serum urea (10.1 [6.2, 15.8] mmol/L vs. 4.7 [3.6, 6.4] mmol/L, Z = 10.545, P < 0.001), IgE (266.0 [86.7, 963.0] IU/ml vs. 142.0 [35.3, 516.5] IU/ml, Z = 2.742, P = 0.007), history of diabetes (6.4% vs. 1.2%, P = 0.009), and history of hypertension (23.9% vs. 5.1%, χ2 = 28.238, P < 0.001) between the AKI group and the non-AKI group. According to multivariate linear regression analysis, among the renal pathological features analyzed, renal tubular epithelial cell damage (β = 178.010, 95% CI: 147.888-208.132, P < 0.001) and renal interstitial edema (β = 28.833, 95% CI: 11.966-45.700, P = 0.001) correlated with serum creatinine values. CONCLUSIONS The percentage of AKI in MCD patients is significantly higher than that in MN patients. Patients over 50 years old are more likely to develop AKI. Renal tubular epithelial cell injury and renal interstitial edema may be the main pathological lesions that are associated with elevated serum creatinine in patients with MCD.
Acute Kidney Injury/etiology* ; Adolescent ; Adult ; Aged ; Child ; Cross-Sectional Studies ; Female ; Humans ; Kidney ; Male ; Middle Aged ; Nephrosis, Lipoid/complications* ; Nephrotic Syndrome/complications* ; Retrospective Studies ; Young Adult

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
Bone Neoplasms ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies

OBJECTIVE: To analyze and characterize the separation effectiveness of self-constructed asymmetrical flow field-flow fractionation system on proteins and lipoproteins, to achieve the optimization of the experimental conditions when separating lipoproteins by orthogonal design test and to investigate the carrier viscosity's influence on separation effectiveness. METHODS: The evaluation of asymmetrical flow field-flow fractionation separation capacity was conducted by using two standard proteins (carbonic anhydrase and thyroglobulin). Under the optimized separation conditions of carbonic anhydrase and thyroglobulin, the channel actual thickness (after assembling, the actual thickness of separation channel was less than initial thickness) was calculated by the analytes' elution time based on the hydrokinetic theory. With orthogonal design test the optimized experimental conditions were studied and statistical analysis was carried on to find out the factors with statistical significance which needed further exploration. RESULTS: According to the hydrodynamics principle and Stoke's function, the channel actual thickness was measured to be 164 μm by separating the two standard proteins, carbonic anhydrase and thyroglobulin, under proper experimental conditions. By the optimization based on orthogonal design test, base-line separation (the resolution had to be higher than 1.50) was achieved. The resolutions of the two experiments were 1.61 and 1.58. According to previous study/ pre-study and supporting theory, in the orthogonal design test, the total 5 factors were integrated for comprehensive investigation: the total flow rate (3.00, 3.50, 4.00, 4.50 mL/min), focus time (3.00, 3.50, 4.00, 4.50 min), transition time (0.5, 1.0, 1.5, 2.0 min), pH of the carrier fluid(6.8, 7.00, 7.20, 7.40) and viscosity of the carrier fluid hydroxypropylmethylcellulose concentration: 0.00%, 0.03%, 0.06%, 1.00%). Among the 5 factors, viscosity was found to have the statistical significance on separation effectiveness which was further investigated. The resolution of high density lipoprotein and low density lipoprotein was increased by the increasing viscosity which also caused more obvious negative spikes. CONCLUSION The separating capacities of self-constructed asymmetrical flow field-flow fractionation system on lipoproteins were verified to be effective and an optimized experimental condition was found to achieve the base-line separation of high density lipoprotein and low density lipoprotein. Viscosity of the carrier fluid was proved to have the statistical significance on lipoprotein separation.
Fractionation, Field Flow ; Lipoproteins ; Lipoproteins, LDL

Objective:To investigate the effects of Sevoflurane on inflammatory response,neuro damage and the prognosis on surgery patients with traumatic brain injury ( TBI ) . Methods:From July 2015 to December 2016, 80 TBI patients undergoing neurosurgery were randomly divided into experimental group ( Sevoflurane treatment, n=40 ) and control group ( n=40 ) . The serum levels of TNF-α,IL-6,C-reactive protein ( CRP) and neuron specific enolase ( NSE) were tested with enzyme linked immunosorbent Assay (ELISA). GCS score,APACHEⅡ score and prognosises of the two groups were also compared. Results:Compared with control group,the serum levels of inflammatory related factors (CRP,TNF-α,IL-6) in the experimental group were significantly decreased in 1 hour of intraoperative,at the end of surgery and on 1st day after surgery respectively ( P<0. 05 or 0. 01 ) . Meanwhile, NSE protein expressions were significantly decreased(P<0. 05 or 0. 01). The experimental group received better prognosis compared to the control group,GCS scores[(10. 82±1. 40) vs (8. 29±1. 02),P=0. 03],APACHEⅡ scores[(14. 42±1. 97) vs (18. 03±2. 15),P=0. 02]on the 14th day. Conclusion:Sevoflurane treatment can effectively regulate the inflammatory response, reduce the neurons damage in surgery patients with TBI,possibly playing brain protection effect.

OBJECTIVETo study the change of TK1 expression level in patients with NHL and its clinical significance.

METHODSA total of 108 NHL patients from July 2013 to January 2016 were chosen, all patients were treated with chemotherapy. The TK1 expression level and TK1 variation rate were compared among CR/PR/PD/DR patients. All patients were followed up, and the relation of TK1 level with OS/PFS was analyzed.

RESULTSAfter treatment, the TK1 expression level of CR/PR/SD patients decreased significantly (P<0.05). Before treatment, the TK1 expression level of CR patients was 1.49±0.34,that after treatment was 0.45±0.17,the variation rate was (68.12±5.41)%; those of PR patients were respectively 2.89±0.58, 1.43±0.29 and (50.27±4.82)%; those of PD patients were respectively 3.98±0.78, 3.71±0.85 and (5.04±0.31)%; and those of SD patients were respectively 3.49±0.92, 2.45±0.57 and (28.65±3.97)%, the difference had statistic significance(P<0.05). After treatment, TK1 level related significantly with OS and PFS (P<0.05).

CONCLUSIONTK1 expression level has suggested implications for the evaluation of tumor loading, and treatment effect as well as prognosis of patients with NHL.