OBJECTIVES: Keratoconus (KC) is a progressive corneal ectasia disorder, arising from a myriad of causes including genetic predispositions, environmental factors, biomechanical influences, and inflammatory reactions. This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population. METHODS: Twenty-five patients with primary KC as well as 50 unrelated population-matched healthy controls, were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population. Sanger sequencing and whole-exome sequencing (WES) were used to analyze mutations in the zinc finger protein 469 (ZNF469) gene. Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis. RESULTS: Five novel heterozygous missense variants were identified in KC patients. Among them, 2 compound heterozygous variants, c.8986G>C (p. E2996Q) with c.11765A>C (p. D3922A), and c.4423C>G (p. L1475V) with c.10633G>A (p. G3545R), were determined to be possible pathogenic factors for KC. CONCLUSIONS Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population. These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
Adolescent ; Adult ; Female ; Humans ; Male ; Case-Control Studies ; China/ethnology* ; Exome Sequencing ; Genetic Predisposition to Disease ; Keratoconus/genetics* ; Mutation ; Mutation, Missense ; Transcription Factors/genetics* ; East Asian People/genetics*

In recent years,artificial intelligence(AI)technologies,particularly those represented by deep learn-ing,have demonstrated tremendous potential in the advancement of medical applications.This article reviews recent re-search progress in AI applications for the diagnosis and treatment of triple-negative breast cancer,aiming to inform the development of clinically relevant AI algorithms that align with real-world practice scenarios.The ultimate objectives in-clude enhancing diagnostic accuracy through efficient computational approaches,reducing manual labor burdens,im-proving patient prognosis,and facilitating the identification of therapeutic targets in oncology through AI-driven predic-tive modeling.

Long non-coding RNAs(lncRNAs)regulate gene expression at the transcriptional,post-transcription-al,or epigenetic levels,and play crucial roles in tumor cell proliferation,invasion,apoptosis,and metabolism.With ongoing research,an increasing number of human microproteins encoded by lncRNAs have been discovered,although their complete functional characterization remains to be explored.This article reviews the research progress on the func-tions and partial mechanisms of the small integral membrane protein(SMIM)family encoded by lncRNAs in tumor ini-tiation and progression.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

Long non-coding RNAs(lncRNAs)regulate gene expression at the transcriptional,post-transcription-al,or epigenetic levels,and play crucial roles in tumor cell proliferation,invasion,apoptosis,and metabolism.With ongoing research,an increasing number of human microproteins encoded by lncRNAs have been discovered,although their complete functional characterization remains to be explored.This article reviews the research progress on the func-tions and partial mechanisms of the small integral membrane protein(SMIM)family encoded by lncRNAs in tumor ini-tiation and progression.

In recent years,artificial intelligence(AI)technologies,particularly those represented by deep learn-ing,have demonstrated tremendous potential in the advancement of medical applications.This article reviews recent re-search progress in AI applications for the diagnosis and treatment of triple-negative breast cancer,aiming to inform the development of clinically relevant AI algorithms that align with real-world practice scenarios.The ultimate objectives in-clude enhancing diagnostic accuracy through efficient computational approaches,reducing manual labor burdens,im-proving patient prognosis,and facilitating the identification of therapeutic targets in oncology through AI-driven predic-tive modeling.

OBJECTIVE To optimize the ultrasound-assisted extraction-deep eutectic solvents technology of total flavonoids from Hypericum japonicum， evaluate its hypoglycemic activity in vitro， and analyze its chemical compositions preliminarily. METHODS The most suitable deep eutectic solvent for total flavonoids from H. japonicum was screened using the composition of hydrogen bond acceptor and donor， molar ratio， water content as factors， and the total flavonoid yield as the response value. Using liquid-solid ratio， ultrasonic power， ultrasonic temperature and ultrasonic time as factors， the yield of total flavonoids as response value， the extraction technology of total flavonoids from H. japonicum was optimized by single-factor experiments combined with Box-Behnken response surface method， and the optimum extraction technology was validated. Taking acarbose as the positive control， the inhibitory activities of total flavonoids from H. japonicum on α-amylase and α-glucosidase in vitro were determined. The chemical constituents of total flavonoids from H. japonicum were analyzed by UPLC combined with comparing the reference substances. RESULTS The most suitable deep eutectic solvent was choline chloride-oxalic acid （the molar ratio of 1∶1， the water content of 30%）. The optimum extraction technology was as follows： the ratio of liquid-solid was 52∶1 （mL/g）， the ultrasonic temperature was 54 ℃ ， the ultrasonic power was 240 W， and the ultrasonic time was 42 min； the total extraction yield of total flavonoids from H. japonicum in 3 validation tests was （73.26±2.48） mg/g， the relative error of which with the theoretical value （73.48 mg/g） was －0.30%. The total flavonoids from H. japonicum could inhibit α-amylase and α-glucosidase with IC50 values of 0.73 and 0.44 mg/mL， respectively， which were higher than those of acarbose （0.23 and 0.15 mg/mL）. UPLC analysis showed that the total flavonoids from H. japonicum contained isoquercetin， quercitrin， quercetin-7-O-α-L-rhamnoside and quercetin. CONCLUSIONS The optimized extraction technology of total flavonoids from H. japonicum is stable and feasible， and the extract has certain hypoglycemic activity in vitro and contains isoquercetin， quercitrin and quercetin-7-O-α-L-rhamnoside， etc.

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 This paper analyzed the characteristics and changes in the disease spectrum of internal medicine inpatients of a tertiary hospital in Zhongshan City.It aimed to explore the evolving trends in disease ranking and treatment charac-teristics to provide a scientific basis for enhancing hospital management.Methods This paper selected 26 053 patients dis-charged from the internal medicine department of the tertiary hospital in Zhongshan City between January 1,2018,and December 31,2022.A retrospective analysis was used to classify these patients by ages,hospitalization date,and relative weight.Results In the past five years,those discharged patients showed no significant increase in the number,but a significant increase in age and ase Mix Index(CMI).Conclusion Since the outbreak of COVID-19,intractable inpatients in the hospital has steadily in-creased in number each year,while the diseases spectrum remains stable.The CMI of circulatory system,respiratory system,and nervous system diseases is relatively high.As key tricky components of internal medicine,these sub-specialties should concentrate on enhancing diagnostic and treatment capabilities as well as service quality to offer improved healthcare services to the public.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*