Apurinic/apyrimidinic endonuclease 1(APE 1)is a multifunctional protein that plays important roles in DNA repair and regulation of gene expression.Because APE 1 is overexpressed in various cancers,it can serve as a cancer biomarker for aiding clinical diagnosis,guiding therapy,and monitoring prognosis.On this basis,a label-free fluorescent probe was designed based on the primer exchange reaction(PER)strategy for highly sensitive detection of APE 1 activity.In the absence of APE 1,the structure of catalytic hairpin(HP)was stable and could not form G-quadruplex.Therefore,the background fluorescence of this sensing system was very low due to the dissociation of thioflavin T(ThT).In the presence of APE 1,the apurinic/apyrimidinic(AP)site of HP was cleaved by APE 1 and a short nucleic acid fragment that acted as a primer to initiate PER was generated.After PER reaction,a large number of G-quadruplex were produced,which could specifically bind with ThT and resulted in significant increase of fluorescence signal.The combination of low background design of HP and PER amplification made this biosensor had high sensitivity with a detection limit(3σ)of 0.0008 U/mL.Furthermore,the primer sequence was directly generated by the cleavage of APE 1 without additional addition,which not only increased the specificity of the reaction,but also simplified the experiment procedure.Moreover,the use of label-free fluorescence signal reduced the cost of the experiment,and realized rapid detection of APE 1.Finally,this sensor was used to detect APE 1 in human serum samples with spiked recoveries of 91%-104%,proving great potential in study of biological enzyme.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

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.

Medical record homepage is a core basis for healthcare quality management, medical insurance payment, and public hospital performance evaluation.The completeness and accuracy of its data directly affect the medical quality and economic benefits of hospitals. Since July 2022, a tertiary hospital had built an auxiliary decision-making system for diagnosis omissions based on artificial intelligence technology, which was officially launched in January 2023. The system aimed to improve the quality of data on the first page of medical records and ensure reasonable payment by medical insurance. This system was built on the hospital′s electronic medical records, and integrated natural language processing, medical knowledge graphs and deep learning technologies to create three engines: diagnosis omission recognition, ICD coding and DRG grouping. The diagnosis omission recognition engine identified both explicit and implicit omitted diagnoses by using a context semantic analysis model and a contrastive learning framework for dual judgment. It also interacted with the ICD coding and DRG grouping engines to enhance the accuracy of DRG grouping. Since its launched, the system has achieved remarkable results. A comparative analysis revealed that the rate of missing diagnoses on hospital medical record homepages has decreased from 31.31% during January to September 2022 to 12.34% during the same period in 2023, and the quality control time for a single medical record had been reduced from 20 minutes to 5 minutes. Additionally, a simulation calculation showed that the system-assisted DRG grouping can increase the hospital′s medical insurance surplus. The system could provide reference and guidance for public hospitals in China to improve the quality of the homepage of medical records and better adapt to medical insurance payment reform.

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.

Medical record homepage is a core basis for healthcare quality management, medical insurance payment, and public hospital performance evaluation.The completeness and accuracy of its data directly affect the medical quality and economic benefits of hospitals. Since July 2022, a tertiary hospital had built an auxiliary decision-making system for diagnosis omissions based on artificial intelligence technology, which was officially launched in January 2023. The system aimed to improve the quality of data on the first page of medical records and ensure reasonable payment by medical insurance. This system was built on the hospital′s electronic medical records, and integrated natural language processing, medical knowledge graphs and deep learning technologies to create three engines: diagnosis omission recognition, ICD coding and DRG grouping. The diagnosis omission recognition engine identified both explicit and implicit omitted diagnoses by using a context semantic analysis model and a contrastive learning framework for dual judgment. It also interacted with the ICD coding and DRG grouping engines to enhance the accuracy of DRG grouping. Since its launched, the system has achieved remarkable results. A comparative analysis revealed that the rate of missing diagnoses on hospital medical record homepages has decreased from 31.31% during January to September 2022 to 12.34% during the same period in 2023, and the quality control time for a single medical record had been reduced from 20 minutes to 5 minutes. Additionally, a simulation calculation showed that the system-assisted DRG grouping can increase the hospital′s medical insurance surplus. The system could provide reference and guidance for public hospitals in China to improve the quality of the homepage of medical records and better adapt to medical insurance payment reform.

Objective To track and evaluate the scientificity, applicability, and operability of the current implementation of the Radiation Shielding Specifications for Radiotherapy Treatment Rooms—Part 2: Radiotherapy Room of Electron Linear Accelerators (GBZ/T 201.2—2011) among personnel in medical radiation technology service institutions, and to provide scientific evidence for further improvement of the standard. Methods Following the Guidelines for Health Standards Tracking Evaluation Work (WS/T 536—2017) and the project implementation plan, a survey was conducted among 140 personnel engaged in shielding testing and evaluation of electron linear accelerator rooms in medical radiation technology service institutions from 24 provinces in China. The methods of pre-investigation, on-site research, mailing, and email were used to collect data for analysis. Results Questionnaires were completed by 140 respondents from 98 medical radiation service institutions, including 63 public institutions and 77 private institutions. Of the surveyed individuals, 86.68% claimed to have a good or very good understanding of the standard, while only 64.3% had participated in training related to the standard. The survey indicated a low level of mastery of the standard content among the personnel and insufficient efforts in training and dissemination. Although only 3.57% of the respondents considered the existing standard to be inapplicable in the context of new radiotherapy equipment and technological advancements, 95.71%, 93.57%, and 96.43% believed that shielding calculation examples should be added for tomotherapy devices, CyberKnife systems, and ring accelerators with self-shielding bodies. Furthermore, 65% of the respondents felt that neutron shielding should be considered for 10 MV X-ray accelerator rooms. Conclusion The GBZ/T 201.2—2011 has been widely used for radiation protection in radiotherapy. However, it is imperative to update this standard. Additionally, due to the technical complexity of the standard, it can be challenging for professionals to fully understand and implement it. Therefore, publicity goals should be tailored to different groups and the training of key personnel should be strengthened. A nationwide communication and cooperation mechanism should be established to ensure uniform implementation of the standard.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

The post-translational modification of proteins is a key mechanism that imparts physiological functions to proteins,among which reversible phosphorylation modifications play a pivotal role in many biological processes.Aberrant changes in phosphorylation are often closely associated with various major disease processes.In recent years,with the aid of proteomic technologies and methods,high-throughput,high-precision qualitative and quantitative approaches for phosphorylated proteins have rapidly advanced.This article reviews the research progress of phosphorylated protein quantification and chemical proteomics analysis methods based on the"bottom-up"strategy,including phosphopeptide enrichment methods,mass spectrometry fragmentation methods,quantification analysis methods and phosphorylation site stoichiometry,and discusses the development trend of quantification and stoichiometric analysis methods for phosphorylated proteins.