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 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.

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.

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.

Objective:To investigate the safety of selective feticide by radiofrequency ablation (RFA) in dichorionic triamniotic (DCTA) triplets and factors related to the clinical outcome.Methods:A retrospective cohort study was designed to review the clinical records and pregnancy outcome of DCTA triplets patients who underwent RFA for selective feticide performed at the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital from January 1,2016 to January 1,2020. Placentas were collected after delivery for gross examination and perfusion study with the mixture of vinylidene chloride and self-curing denture acrylic.Results:A total of 12 DCTA cases were recruited. Selective feticide by RFA were performed at a mean gestational age of 15.6 weeks, and cases delivered at a mean gestational age of 36.9 weeks (34 +4-38 +2 weeks). Eight of the cases undertook invasive prenatal diagnosis weeks after RFA. The interval between RFA to delivery and gestational ages at delivery were similar between women undertook prenatal diagnosis and those who did not ( P>0.05). Six of the 23 newborns (26%) were small for gestational age. The average birth weight of either monochorionic singleton fetus or the remained co-twin of the monochorionic diamniotic (MCDA) twin as lower than that of singleton pregnancy ( P<0.001). One case of DCTA (8.3%) underwent intrauterine fetal death of the MCDA co-twin 4 h after RFA. Fetal tachycardia and cessation of fetal movement of the co-twin were observed before death. By the time of delivery, placental examination revealed the pale anemia look of the placental part of the co-twin and the reddish appearance of the part of the reduced fetus, which suggested a hypovolemic shock after an uncompleted RFA as the cause of co-twin death. A total of 10 MCDA placentas from cases with a living MCDA co-twins were collected. Various degree of placental perfusion on the reduced fetal side of placenta was noticed in nine cases. The co-twin with the placenta which did not have such kind of perfusion had a birth weight at the lowest percentile. Conclusion:Selective feticide by RFA is a safe procedure for DCTA triplet, and prenatal diagnosis has no adverse impact on pregnancy outcome. Ultrasound monitoring of fetal heart rate and fetal movement of the MCDA co-twin after RFA is helpful for predicting clinical outcome. Postnatal placental examination provides clues for adverse outcome, and the growth potential of the MCDA co-twin might be related to the type of anastomosis between the two fetuses.

Objective:To investigate the safety of selective feticide by radiofrequency ablation (RFA) in dichorionic triamniotic (DCTA) triplets and factors related to the clinical outcome.Methods:A retrospective cohort study was designed to review the clinical records and pregnancy outcome of DCTA triplets patients who underwent RFA for selective feticide performed at the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital from January 1,2016 to January 1,2020. Placentas were collected after delivery for gross examination and perfusion study with the mixture of vinylidene chloride and self-curing denture acrylic.Results:A total of 12 DCTA cases were recruited. Selective feticide by RFA were performed at a mean gestational age of 15.6 weeks, and cases delivered at a mean gestational age of 36.9 weeks (34 +4-38 +2 weeks). Eight of the cases undertook invasive prenatal diagnosis weeks after RFA. The interval between RFA to delivery and gestational ages at delivery were similar between women undertook prenatal diagnosis and those who did not ( P>0.05). Six of the 23 newborns (26%) were small for gestational age. The average birth weight of either monochorionic singleton fetus or the remained co-twin of the monochorionic diamniotic (MCDA) twin as lower than that of singleton pregnancy ( P<0.001). One case of DCTA (8.3%) underwent intrauterine fetal death of the MCDA co-twin 4 h after RFA. Fetal tachycardia and cessation of fetal movement of the co-twin were observed before death. By the time of delivery, placental examination revealed the pale anemia look of the placental part of the co-twin and the reddish appearance of the part of the reduced fetus, which suggested a hypovolemic shock after an uncompleted RFA as the cause of co-twin death. A total of 10 MCDA placentas from cases with a living MCDA co-twins were collected. Various degree of placental perfusion on the reduced fetal side of placenta was noticed in nine cases. The co-twin with the placenta which did not have such kind of perfusion had a birth weight at the lowest percentile. Conclusion:Selective feticide by RFA is a safe procedure for DCTA triplet, and prenatal diagnosis has no adverse impact on pregnancy outcome. Ultrasound monitoring of fetal heart rate and fetal movement of the MCDA co-twin after RFA is helpful for predicting clinical outcome. Postnatal placental examination provides clues for adverse outcome, and the growth potential of the MCDA co-twin might be related to the type of anastomosis between the two fetuses.