[Clinicopathological and molecular genetic features of Crohn's disease].

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.

[Retrospective analysis of infliximab in the treatment of Kawasaki disease].

Objective: To investigate the efficacy and safety of infliximab (IFX) therapy for children with Kawasaki disease. Methods: Sixty-eight children with Kawasaki disease who received IFX therapy in Children's Hospital of Fudan University from January 2014 to April 2021 were enrolled. The indications for IFX administration, changes in laboratory parameters before and after IFX administration, response rate, drug adverse events and complications and outcomes of coronary artery aneurysms (CAA) were retrospectively analyzed. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Results: Among 68 children with Kawasaki disease, 52 (76%) were males and 16 (24%) were females. The age of onset was 2.1 (0.5, 3.8) years. IFX was administered to: (1) 35 children (51%) with persistent fever who did not respond to intravenous immunoglobulin (IVIG) or steroids, 28 of the 35 children (80%) developed CAA before IFX therapy; (2) 32 children (47%) with continuous progression of CAA; (3) 1 child with persistent arthritis. In all cases, IFX was administered as an additional treatment (the time from the onset of illness to IFX therapy was 21 (15, 30) days) which consisted of second line therapy in 20 (29%), third line therapy in 20 (29%), and fourth (or more) line therapy in 28 (41%). C-reactive protein (8 (4, 15) vs. 16 (8, 43) mg/L, Z=-3.38, P=0.001), serum amyloid protein A (17 (10, 42) vs. 88 (11, 327) mg/L, Z=-2.36, P=0.018) and the percentage of neutrophils (0.39±0.20 vs. 0.49±0.21, t=2.63, P=0.010) decreased significantly after IFX administration. Fourteen children (21%) did not respond to IFX and received additional therapies mainly including steroids and cyclophosphamide. There was no significant difference in gender, age at IFX administration, time from the onset of illness to IFX administration, the maximum coronary Z value before IFX administration, and the incidence of systemic aneurysms between IFX-sensitive group and IFX-resistant group (all P>0.05). Infections occurred in 11 cases (16%) after IFX administration, including respiratory tract, digestive tract, urinary tract, skin and oral infections. One case had Calmette-Guérin bacillus-related adverse reactions 2 months after IFX administration. All of these adverse events were cured successfully. One child died of CAA rupture, 6 children were lost to follow up, the remaining 61 children were followed up for 6 (4, 15) months. No CAA occurred in 7 children before and after IFX treatment, while CAA occurred in 54 children before IFX treatment. CAA regressed in 23 (43%) children at the last follow-up, and the diameter of coronary artery recovered to normal in 10 children. Conclusion: IFX is an effective and safe therapeutic choice for children with Kawasaki disease who are refractory to IVIG or steroids therapy or with continuous progression of CAA.

[Regression analysis of cerebral blood perfusion and cognitive function in patients with mild cognitive impairment and Alzheimer's disease].

Objective: To analyze the relationships between cerebral blood perfusion and impairments of cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A total of 21 patients with AD, 18 patients with MCI and 21 healthy adults as control group (NC group) matched in age, gender and education were recruited between November 2016 and November 2017 from Northern Jiangsu People's Hospital. All cases were performed routine head MRI, arterial spin labeling (ASL). Cognitive function evaluation including simple mental state scale (MMSE) and improved Addenbrooke's cognitive examination revised (ACE-R) of patients were also assessed. The difference between cerebral blood perfusion signals and cognitive impairment of the three groups were analyzed. Results: The subtest scores of attention and orientation, memory, language fluency, language and visual space of ACE-R scores were significantly reduced (P<0.001,uncorrected) for AD when compared with MCI. Using REST1.8 software to perform single factor ANOVA, and adjusted for P<0.05. The AD group showed a decrease in total cerebral perfusion compared to the NC group, a decrease and in the frontotemporal lobe compared to MCI group; compared with the normal group, MCI group also showed decreased perfusion in frontotemporal cortex. Pearson correlation analysis was performed on the cerebral blood flow and ACE-R scores in the AD group and the MCI group,the decrease degree of CBF in multiple brain regions was positively correlated with the total score of ACE-R's total scores, and the subtest score of ACE-R including attention and orientation, memory, language fluency, language and visual space also showed positive correlation. Conclusion: ASL technology can detect the changes of cerebral blood flow metabolism in AD and MCI patients, and reveal association relationships between brain function damage and cerebral blood flow metabolism in AD and MCI patients.

Association of genetic polymorphisms of de novo nucleotide biosynthesis with increased CHD susceptibility in the northern Chinese population.

Congenital heart disease (CHD) is one of most prevalent birth defects in the world. However, the underlying molecular mechanism(s) have not been fully understood. Here we report that increased CHD susceptibility is associated with genetic polymorphisms for de novo nucleotide biosynthesis in northern Chinese population, which has been reported with lower plasma folate levels. Nine tagSNPs of four genes (GART, ATIC, MTHFD1 and SHMT1) in de novo nucleotide biosynthesis were sequenced in 802 sporadic CHD patients and 1093 controls from two Han Chinese populations, located in north China (Shandong) and South China (Shanghai), respectively. Six SNPs were found to be significantly associated with CHDs or septation defects only in the Shandong population dataset, but none displayed significant association with any CHDs in the Shanghai population dataset as well as in the combined dataset. We also showed that the minor A allele of rs7279549 in GART reduced transcriptional activity and displayed lower affinity for unknown transcription factor(s), demonstrating the allele is a functional risk factor for CHD in Shandong population. Our study indicates that dysregulation of de novo nucleotide biosynthesis pathway may conditionally contribute to CHD pathogenesis in northern Chinese.

High preoparative levels of serum periostin are associated with poor prognosis in patients with hepatocellular carcinoma after hepatectomy.

AIMS: Periostin (POSTN) is implicated in cancer development and progression. The aim of this study was to evaluate the diagnostic and prognostic significance of serum POSTN in patients with hepatocellular carcinoma (HCC) receiving curative surgery. METHODS: Enzyme-linked immunosorbent assay was performed to determine serum POSTN levels in 69 healthy volunteers, 30 patients with hepatolithiasis, 27 patients with cirrhosis, and 56 HCC patients. The relationships between serum POSTN and clinicopathologic features were analyzed. Receiver operating characteristics analysis was used to calculate diagnostic accuracy of serum POSTN, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of serum POSTN on overall survival (OS) and relapse-free survival (RFS) was also investigated. RESULTS: The median serum POSTN level was significantly (P < 0.05) increased in HCC patients, compared to healthy controls, patients with hepatolithiasis, and patients with liver cirrhosis. Elevated serum POSTN was only significantly associated with Edmondson grade (P = 0.007). The combination of serum POSTN and AFP had a markedly higher area under the curve (0.805 (95% confidence interval [CI]: 0.677-0.932)) than POSTN (0.582 (95% CI: 0.427-0.736)) or AFP (0.655 (95% CI: 0.504-0.806)) alone. Kaplan-Meier analysis indicated that elevated serum POSTN was associated with OS (P = 0.031) and RFS (P = 0.027). Moreover, multivariate analysis revealed elevated serum POSTN as an independent poor prognostic marker for OS and RFS. CONCLUSIONS: Preoperative serum POSTN has limited diagnostic value in distinguishing HCC from non-malignant liver diseases, but serves as independent prognostic biomarker in HCC patients.

Desolvation of macromolecules by ultrafast heating: A molecular-dynamics study.

Using molecular-dynamics simulation, we investigate the consequences of ultrafast laser-induced heating of a water droplet containing a solvated polymer, using the example of a 1 ps laser irradiation. We study the isolation process and the properties of the isolated polymer as a function of the polymer size, the droplet size, and the temperature to which the droplet is heated. We find that the isolation process occurs on a time scale of a few ten ps. The final polymer temperature increases linearly with the heating. Polymers embedded in larger droplets acquire higher temperatures, while larger polymers are less heated. In spite of the ultrafast heating, the isolated polymer remains in its coiled conformation.

Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway.

The aim of present study is to explore the cytoprotection of curcumin against 1-methyl-4-phenylpridinium ions (MPP(+))-induced apoptosis and the molecular mechanisms underlying in PC12 cells. Our findings indicated that MPP(+) significantly reduced the cell viability and induced apoptosis of PC12 cells. Curcumin protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by inducing overexpression of Bcl-2, but also reducing the loss of mitochondrial membrane potential (MMP), an increase in intracellular reactive oxygen species (ROS) and overexpression of inducible nitric oxide synthase (iNOS). The selective iNOS inhibitor AG partly blocked MPP(+)-induced apoptosis of PC12 cells. The results of present study suggested that the cytoprotective effects of curcumin might be mediated, at least in part, by the Bcl-2-mitochondria-ROS-iNOS pathway. Because of its non-toxic property, curcumin could be further developed to treat the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease (PD).

Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.

The aim of this study was to investigate the role of JAK-STAT pathway in the cytoprotection afforded by preconditioning with H(2)O(2). It was shown that (1) Preconditioning with 100 micromol/L H(2)O(2) can markedly protect PC12 cells against apoptosis and cytotoxicity induced by 300 micromol/L H(2)O(2); (2) The expression and tyrosine phosphorylation of JAK2, not JAK1 were rapidly increased at 5 min after H(2)O(2) preconditioning; (3) The expression of STAT1 and STAT3 were significantly increased at 15 min after H(2)O(2) preconditioning, and the pTyr-STAT1 and pTyr-STAT3 were markedly increased at 60 min after H(2)O(2) preconditioning; (4) Pretreatment with the JAK inhibitor AG-490 (10 micromol/L) 20 min before H(2)O(2) preconditioning blocked not only the activation of JAK2, STAT1 and STAT3, but also the cytoprotection of H(2)O(2) preconditioning against apoptosis and cytotoxicity induced by oxidative stress. These findings suggested that preconditioning with H(2)O(2) activated the JAK-STAT pathway that played an important role in the cytoprotection induced by H(2)O(2) preconditioning.