DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

The anti-inflammatory effect of simplified Zhiqin Decoction was observed by using lipopolysaccharide (LPS)-induced inflammation mouse model. The main chemical constituents and the main mechanism of action of simplified Zhiqin Decoction were predicted by network pharmacology. Animal experiments verified the anti-inflammatory mechanism of simplified Zhiqin Decoction (this experiment was approved by the Animal Experiment Ethics Committee of Southwest University, approval number: IACUC-20210825-02). Simplifying Zhiqin Decoction has a significant anti-inflammatory effect on inflammatory mice, can significantly improve the overall macro shape of mice, reduce body temperature, water intake, increase the number of autonomous activities; alleviate liver, lung, spleen, thymus inflammation and pathological damage; decrease tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, nitric oxide (NO), prostaglandin E₂ (PGE₂) content in serum and urine. The contents of serum immune factors IgG, IgA and IgM were increased. Network pharmacology predicted 66 potential anti-inflammatory active components of simplified Zhiqin Decoction involving 132 inflammatory targets, and the key anti-inflammatory signaling pathway involved PI3K/AKT, TNF, JAK-STAT, etc. Animal experiments show that simplified Zhiqin Decoction can significantly reduce the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway related proteins in lung tissue of inflammatory mice. The results of this study showed that simplified Zhiqin Decoction had significant anti-inflammatory effects, and its main anti-inflammatory components were quercetin, β-sitosterol, kaempferol, wogonin, stigmasterol, luteolin, neobaicalein, etc. The main mechanism of its anti-inflammatory action is that it significantly inhibits the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway protein.

Objective To investigate the diagnostic value of 62-slice spiral CT and its post-processing techniques for tibial plateau fracture(TPF)and its influence on treatment regimens selection.Methods A total of 173 TPF patients diagnosed and treated in our hospital from January 2021 to December 2022 were included,and the diagnostic accuracy,classification diagostic accuracy and fracture collapse degree accuracy of X-ray and CT scans were compared,with surgical and pathological diagnosis as the gold standard.Results CT and its post-processing technique can more clearly show the direction of fracture line,the displacement direction of fracture fragments and the collapse degree of articular surface than X-ray.The fracture morphology of 171 patients seen during the operation was consistent with CT and its post-processing images.The diagnostic accuracy of X-ray for TPF was 93.64%,which was lower than that of CT and its post-processing techniques(98.84% ),and the difference was statistically significant(χ2=6.474,P=0.011).The overall accuracy of X-ray in evaluating the degree of fracture collapse was significantly lower than that of CT 3D reconstruction(65.32% vs.90.75%;χ2=32.644,P<0.001).The total accuracy of CT and its post-processing techniques for TPF Schatzker classification(97.69% )was higher than that of X-ray(88.44% ),and the difference was statistically significant(χ2=11.462,P=0.001).Different CT reconstruction models had statistically significant difference on the total accuracy of TPF Schatzker classification diagnosis(χ2=40.647,P<0.001),and the diagnosis accuracy of volume reconstruction was the highest(96.53% ).Conclusion The application of CT and its post-processing techniques can effectively evaluate TPF,articular surface collapse and fracture classification,and provide imaging reference for clinical decision-making.

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.
Mice ; Animals ; Heart Failure/metabolism* ; Stroke Volume ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Metabolomics ; Arachidonic Acids ; Proline

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg² combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.
Adult ; Humans ; Male ; Female ; Adolescent ; Young Adult ; Middle Aged ; Aged ; Non-alcoholic Fatty Liver Disease/pathology* ; Diabetes Mellitus, Type 2/pathology* ; Liver/pathology* ; Obesity/pathology* ; Apolipoproteins A

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Humans ; Otitis Media, Suppurative ; Chronic Disease ; Biofilms ; Otitis Media

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.
Female ; Humans ; Albinism, Oculocutaneous/genetics* ; DNA Copy Number Variations ; Membrane Transport Proteins/genetics* ; Molecular Biology ; Mutation ; Infant

Humans ; Receptors, Chimeric Antigen ; Hematopoietic Stem Cell Transplantation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Immunotherapy, Adoptive ; Antigens, CD19