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.

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

ObjectiveTo investigate the distribution and trend of rehabilitation personnel of China Disabled Persons' Federation (CDPF) system and the people with disabilities (PWDs) using geographical gravity model. MethodsBased on ArcGIS and statistical data, the distribution of geographical center of gravity of the rehabilitation personnel of the CDPF system from 2011 to 2021 was analyzed. According to the economic development, the areas were divided into three regions, and the eastern region included eleven provincial units, the central region includes eight provincial units, and the western region included twelve provincial units. ResultsCompared with 2011, rehabilitation staffs per thousand PWDs increased at 107.5% in 2021, 81.1%, 114.2% and 174.1% for the eastern, central, and western regions, respectively; professional staffs increased at 190.5%, 148.8%, 284.6% and 280.6% for the eastern, central, and western regions, respectively; managerial staff increased at 80.0%, 46.8%, 554.3% and 128.1% for the eastern, central, and western regions, respectively. Compared with 2011, the geographical center of gravity of the rehabilitation personnel moved about 330.9 km in 2021, while the geographical center of gravity of the PWDs moved about 169.64 km. ConclusionThe rehabilitation personnel in the CDPF system is the most in the eastern region and least in the western region. The tracks of the geographical center of gravity of the three kind of rehabilitation personnel in the CDPF system are relatively consistent. The rehabilitation personnel in the eastern region are more concentrated than those in the western region, and the density of the PWDs is more westward than that of the rehabilitation personnel, and coordination is not a perfect match yet. It is necessary to strengthen the rehabilitation personnel allocation in the western region, to balance distribution of human resources for rehabilitation of PWDs among regions.