ObjectiveTo investigate the distribution and characteristics of traditional Chinese medicine （TCM） syndromes in patients with colorectal cancer and metabolic dysfunction-associated fatty liver disease （CRC-MAFLD）， to explore the correlation between influencing factors and syndrome distribution， and to provide a reference for clinical syndrome differentiation. MethodsA total of 319 patients who were admitted to Shanxi Provincial Institute of Traditional Chinese Medicine and The Affiliated Hospital of Shanxi University of Chinese Medicine from January 2021 to December 2025 and were diagnosed with CRC-MAFLD based on pathology and radiological examination were enrolled as subjects， and TCM syndrome differentiation was performed for all subjects. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between multiple groups. The indicators with statistical significance in the univariate analysis were incorporated into the unordered multinomial Logistic regression model， and the syndrome of liver depression and spleen deficiency was set as the reference group to identify the independent influencing factors for each TCM syndrome. ResultsThe main clinical symptoms of CRC-MAFLD included fatigue （78.06%）， abdominal distension （64.26%）， poor appetite （61.13%）， loose stool （57.05%）， and costal pain （52.04%）. The syndrome of liver depression and spleen deficiency showed the highest distribution frequency， followed by intermingled phlegm and blood stasis， internal retention of dampness turbidity， damp-heat accumulation， deficiency of liver and kidney， and deficiency of spleen and kidney. Comparison between groups with different TCM syndromes showed significant differences in the distribution of body mass index （χ²=42.216， P<0.001）， the clinical stage of colorectal cancer （χ²=11.666， P=0.040）， liver metastasis （χ²=19.279， P=0.002）， degree of hepatic steatosis （χ²=71.085， P<0.001）， diabetes （χ²=12.486， P=0.029）， chemotherapy （χ²=21.920， P<0.001）， fasting plasma glucose （FPG） （F=10.367， P<0.001）， glycosylated hemoglobin （HbA1c） （F=3.696， P=0.003）， albumin （Alb） （F=3.302， P=0.006）， alkaline phosphatase （ALP） （H=34.350， P<0.001）， gamma-glutamyl transferase （GGT） （H=41.679， P<0.001）， and triglyceride （TG） （H=28.826， P<0.001）. An unordered multinomial Logistic regression model was constructed with the syndrome of liver depression and spleen deficiency as the reference， and the results showed that overweight/obesity was a common independent risk factor for intermingled phlegm and blood stasis （odds ratio ［OR］=4.468， P=0.002）， internal retention of dampness turbidity （OR=2.944， P=0.024）， and damp-heat accumulation （OR=5.651， P=0.001）； clinical stage Ⅳ was an independent risk factor for deficiency of liver and kidney （OR=6.746， P=0.003） and deficiency of spleen and kidney （OR=10.074， P=0.001）； presence of liver metastasis was an independent risk factor for intermingled phlegm and blood stasis （OR=5.145， P=0.001）； severe fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=5.201， P=0.007） and internal retention of dampness turbidity （OR=7.412， P=0.001）， and moderate fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=2.643， P=0.045）， internal retention of dampness turbidity （OR=3.182， P=0.029）， and damp-heat accumulation （OR=3.073， P=0.036）； diabetes was an independent risk factor for internal retention of dampness turbidity （OR=5.133， P=0.003） and damp-heat accumulation （OR=3.716， P=0.031）. As for continuous variables， elevated FPG was an independent risk factor for internal retention of dampness turbidity （OR=2.375， P=0.003） and damp-heat accumulation （OR=2.701， P=0.005）； elevated HbA1c was an independent risk factor for intermingled phlegm and blood stasis （OR=2.029， P=0.032） and deficiency of liver and kidney （OR=3.308， P=0.010）； elevated ALP was an independent risk factor for damp-heat accumulation （OR=1.053， P=0.019）； elevated GGT was an independent risk factor for intermingled phlegm and blood stasis （OR=1.029， P=0.026） and damp-heat accumulation （OR=1.030， P=0.047）； elevated TG was an independent risk factor for intermingled phlegm and blood stasis （OR=2.931， P=0.006） and internal retention of dampness turbidity （OR=2.449， P=0.019）； elevated Alb was a protective factor against deficiency of spleen and kidney （OR=0.756， P=0.005）. ConclusionBody mass index， the clinical stage of colorectal cancer， liver metastasis， degree of hepatic steatosis， diabetes， chemotherapy， FPG， HbA1c， Alb， ALP， GGT， and TG are the main influencing factors for TCM syndromes in CRC-MAFLD.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Sennoside A(SA),a typical prodrug,exerts its laxative effect only after its transformation into rhei-nanthrone catalyzed by gut microbial hydrolases and reductases.Hydrolases have been identified,but reductases remain unknown.By linking a photoreactive group to the SA scaffold,we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling(ABPP).From lysates of an active strain,Bifidobacterium pseudocatenulatum(B.pseu-docatenulatum),397 proteins were enriched and subsequently identified using mass spectrometry(MS).Among these proteins,chromate reductase/nicotinamide adenine dinucleotide(NADH)phosphate(NADPH)-dependent flavin mononucleotide(FMN)reductase/oxygen-insensitive NADPH nitroreductase(nfrA)was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource(UniProt)database screening.We also determined that recombinant nfrA could reduce SA.Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective To detect and identify the differentially expressed tsRNA in the serum of patients with Sj?gren's syndrome(SS),and preliminarily explore their potential application value in the diagnosis of SS.Methods The serum samples from SS patients diagnosed at the Rheumatology Department of Nanjing Drum Tower Hospital and healthy controls(HCs)matched age and gender were collected,and the differentially expressed tsRNA were screened by small RNA sequencing.Fluorescence quantitative real-time PCR(qRT-PCR)was used to valid the sequence data.The receiver operating characteristic(ROC)curve was used to evaluate the diagnos-tic efficiency of tRNA-Gly-GCC-1-1.KEGG and GO analysis were used to predict the potential mechanism of tRNA-GLy-GCC-1-1 in the occurrence and development of SS.Results Compared with HCs(13.34[10.45,18.74]fmol/L),the levels of serum tRNA-Gly-GCC-1-1 in SS patients(8.82[7.26,12.20]fmol/L)were significantly reduced(P＜0.000 1),and its area under the ROC curve(AUCROC)in distinguishing SS patients from HCs was 0.766(95%CI:0.671-0.861).When the cut-off value was 9.97 fmol/L,its sensitivity and specificity were 83.33%and 64.58%,respectively.Bioinformatics analysis showed that serum tRNA-Gly-GCC-1-1 might be involved in the regulation of signaling pathways such as PI3K-Akt.Conclusion Serum tRNA-Gly-GCC-1-1 in SS patients is significantly down-regulated,which has potential clinical application value in assisting the diagnosis of SS.

Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.

Objective To detect and identify the differentially expressed tsRNA in the serum of patients with Sj?gren's syndrome(SS),and preliminarily explore their potential application value in the diagnosis of SS.Methods The serum samples from SS patients diagnosed at the Rheumatology Department of Nanjing Drum Tower Hospital and healthy controls(HCs)matched age and gender were collected,and the differentially expressed tsRNA were screened by small RNA sequencing.Fluorescence quantitative real-time PCR(qRT-PCR)was used to valid the sequence data.The receiver operating characteristic(ROC)curve was used to evaluate the diagnos-tic efficiency of tRNA-Gly-GCC-1-1.KEGG and GO analysis were used to predict the potential mechanism of tRNA-GLy-GCC-1-1 in the occurrence and development of SS.Results Compared with HCs(13.34[10.45,18.74]fmol/L),the levels of serum tRNA-Gly-GCC-1-1 in SS patients(8.82[7.26,12.20]fmol/L)were significantly reduced(P＜0.000 1),and its area under the ROC curve(AUCROC)in distinguishing SS patients from HCs was 0.766(95%CI:0.671-0.861).When the cut-off value was 9.97 fmol/L,its sensitivity and specificity were 83.33%and 64.58%,respectively.Bioinformatics analysis showed that serum tRNA-Gly-GCC-1-1 might be involved in the regulation of signaling pathways such as PI3K-Akt.Conclusion Serum tRNA-Gly-GCC-1-1 in SS patients is significantly down-regulated,which has potential clinical application value in assisting the diagnosis of SS.

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a"depict"strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample prep-aration of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

Objective The segmented regression model designed by interruption time series was used to analyze the short-term and long-term effects of antimicrobial management and prevention of nosocomial infection,so as to provide methodological reference for the effect evaluation of public health interventions.Methods The data of nosocomial infection with Klebsiella pneumoniae(KPN)in a third class hospital in Shanxi Province from July 2017 to June 2020 were collected and analyzed by Poisson piecewise regression model with interrupted time series adjusted for outliers.Results The short-term intervention effect was better after the implementation of antibiotics management.The risk of KPN infection after the intervention was 81.25%before the intervention(P<0.05),and the risk of infection with Klebsiella pneumoniae decreased by 18.75%.However,the effect of long-term intervention is poor.For each additional month,the risk of infection will increase by 1.55%.Because of the large proportion of serious ill patients during the COVID-19 period,the KPN infection rate in the hospital increased,and the infection risk increased by 68.81%.Conclusion The implementation of antimicrobial drug management only reduces the risk of KPN infection in the short term,which needs to be strictly implemented in the long term to play a lasting role.Considering the interruption time series of outliers,the piecewise regression model can not only quantitatively evaluate the short-term and long-term intervention effects,but also analyze the risks caused by outliers,so as to provide methodological reference for the effect evaluation of public health interventions.

Objective The segmented regression model designed by interruption time series was used to analyze the short-term and long-term effects of antimicrobial management and prevention of nosocomial infection,so as to provide methodological reference for the effect evaluation of public health interventions.Methods The data of nosocomial infection with Klebsiella pneumoniae(KPN)in a third class hospital in Shanxi Province from July 2017 to June 2020 were collected and analyzed by Poisson piecewise regression model with interrupted time series adjusted for outliers.Results The short-term intervention effect was better after the implementation of antibiotics management.The risk of KPN infection after the intervention was 81.25%before the intervention(P<0.05),and the risk of infection with Klebsiella pneumoniae decreased by 18.75%.However,the effect of long-term intervention is poor.For each additional month,the risk of infection will increase by 1.55%.Because of the large proportion of serious ill patients during the COVID-19 period,the KPN infection rate in the hospital increased,and the infection risk increased by 68.81%.Conclusion The implementation of antimicrobial drug management only reduces the risk of KPN infection in the short term,which needs to be strictly implemented in the long term to play a lasting role.Considering the interruption time series of outliers,the piecewise regression model can not only quantitatively evaluate the short-term and long-term intervention effects,but also analyze the risks caused by outliers,so as to provide methodological reference for the effect evaluation of public health interventions.