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 efficacy and safety of venetoclax combined with reduced dose HAD regimen in the treatment of newly diagnosed acute myeloid leukemia (AML) was investigated. From May 2022 to January 2023, a total of 25 patients with newly diagnosed AML were treated with venetoclax combined with reduced-dose HAD regimen as induction therapy. Accoding to the 2017 ELN recommendations, 13 (52.0%) in favoable, 3 (12.0%) in intemediate, and 9 (36.0%) in adverse. The ORR (CR rate+PR rate) was 88.0%, and the CR rate was 84.0%. By May 30, 2023, with a median follow-up of 9 months, 1 year overall survival, event-free survival, and relapse-free survival were 100%, 94.7%, and 94.7%, respectively. All patients received 1-5 cycles of consolidation therapy and two median cycles. Treatment with venetoclax and reduced dose of HAD regimen in the treatment of patients with newly diagnosed AML was high effective and safe.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Objective: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. Methods: Data of patients who had been treated for stage I–II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failurefree survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell’s C-index, calibration curves and receiver operating characteristic (ROC) curves. Results: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2–15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. Conclusion Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

OBJECTIVE: To analyze the spatial distribution of the prevalence of cognitive dysfunction and its risk factors in Chinese population aged 45 years and above to provide evidence for formulating regional prevention and control strategies. METHODS: The study subjects with complete cognitive function data were selected from the follow-up data of the China Health and Retirement Longitudinal Study (CHARLS) Phase IV. ArcGis 10.4 software was used for spatial analysis of the prevalence of cognitive dysfunction in the population aged 45 years and above for each province based on the geographic information system (GIS) technology. RESULTS: In 2018, the overall prevalence of cognitive dysfunction was 33.59% (5951/17716) in individuals aged 45 and above in China. Global spatial autocorrelation analysis indicated a spatial clustering and a positive autocorrelation (P < 0.001) of the prevalence of cognitive dysfunction in the study subjects, with a Moran's I value of 0.333085. The results of local spatial autocorrelation analysis showed that the southwestern region of China was the main aggregation area of patients with cognitive dysfunction. Geographically weighted regression analysis suggested that a male gender, an advanced age, and illiteracy were the major risk factors for cognitive dysfunction (P < 0.05). These 3 risk factors showed a spatial distribution heterogeneity with greater impact in the northern, western, and northwestern regions of China, respectively. CONCLUSION The prevalence of cognitive dysfunction is relatively high in individuals aged 45 years and above in China. A male gender, an advanced age, and illiteracy are the major risk factors for cognitive dysfunction and show different spatial distribution patterns, with the northern, western and northwestern regions of China as the key areas for prevention and control, where the prevention and control measures should be designed based on local conditions.
Humans ; Male ; China/epidemiology* ; Cluster Analysis ; Cognitive Dysfunction/epidemiology* ; East Asian People ; Longitudinal Studies ; Risk Factors ; Middle Aged

OBJECTIVE: To investigate the incidence trend and spatial clustering characteristics of scarlet fever in China from 2016 to 2020 to provide evidence for development of regional disease prevention and control strategies. METHODS: The incidence data of scarlet fever in 31 provinces and municipalities in mainland China from 2016 to 2020 were obtained from the Chinese Health Statistics Yearbook and the Public Health Science Data Center led by the Chinese Center for Disease Control and Prevention.The three-dimensional spatial trend map of scarlet fever incidence in China was drawn using ArcGIS to determine the regional trend of scarlet fever incidence.GeoDa spatial autocorrelation analysis was used to explore the spatial aggregation of scarlet fever in China in recent years. RESULTS: From 2016 to 2020, a total of 310 816 cases of scarlet fever were reported in 31 provinces, municipalities directly under the central government and autonomous regions, with an average annual incidence of 4.48/100 000.The reported incidence decreased from 4.32/100 000 in 2016 to 1.18/100 000 in 2020(Z=103.47, P < 0.001).The incidence of scarlet fever in China showed an obvious regional clustering from 2016 to 2019(Moran's I>0, P < 0.05), but was randomly distributed in 2020(Moran's I>0, P=0.16).The incidence of scarlet fever showed a U-shaped distribution in eastern and western regions of China, and increased gradually from the southern to northern regions.Inner Mongolia Autonomous Region and Hebei and Gansu provinces had the High-high (H-H) clusters of scarlet fever in China. CONCLUSION Scarlet fever still has a high incidence in China with an obvious spatial clustering.For the northern regions of China with H-H clusters of scarlet fever, the allocation of health resources and public health education dynamics should be strengthened, and local scarlet fever prevention and control policies should be made to contain the hotspots of scarlet fever.
Humans ; Incidence ; Scarlet Fever/epidemiology* ; China/epidemiology* ; Spatial Analysis ; Cluster Analysis ; Spatio-Temporal Analysis

Dental resin composites (DRCs) are popular materials for repairing caries or dental defect, requiring excellent properties to cope with the complex oral environment. Filler/resin interface interaction has a significant impact on the physicochemical/biological properties and service life of DRCs. Various chemical and physical modification methods on filler/resin interface have been introduced and studied, and the physical micromechanical interlocking caused by the modification of fillers morphology and structure is a promising method. This paper firstly introduces the composition and development of DRCs, then reviews the chemical and physical modification methods of the filler/resin interface, mainly discusses the interface micromechanical interlocking structures and their enhancement mechanism for DRCs, finally give a summary on the existing problems and development potential.
Composite Resins/chemistry* ; Surface Properties ; Materials Testing

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.