ObjectiveThe biosynthesis of heterophyllin B （HB）， a cyclopeptide from Pseudostellaria heterophylla， is regulated by various abiotic stresses. Elucidating the transcriptional regulatory mechanism underlying HB biosynthesis is of great guiding significance for the directional improvement of P. heterophylla varieties and the enhancement of HB content. MethodsBased on transcriptome data from different tissues of P. heterophylla， transcription factors （TFs） specifically upregulated and highly expressed in the phloem of tuberous roots were screened through a combination of Mfuzz time-series clustering， transcription factor family prediction， and correlation analysis. Quantitative real-time polymerase chain reaction （Real-time PCR） was employed to analyze expression patterns of candidate TFs under abscisic acid （ABA） induction， and the dual-luciferase reporter assay was applied to verify their regulatory effects on HB precursor genes. ResultsContent determination showed that HB accumulated at the highest in the phloem of P. heterophylla tuberous roots （34 μg·g^-1 fresh weight）. Transcriptome analysis identified 15 868 up-regulated differentially expressed genes （DEGs）， among which 4 375 were specifically up-regulated in the phloem. From these， 25 TFs highly expressed in the phloem were screened. Correlation analysis revealed that the expression level of WRKY70 was significantly positively correlated with HB content， the expression of precursor genes prePhHB， and PhPOP1. Additionally， WRKY70 expression was significantly upregulated under ABA induction. Dual-luciferase reporter assay confirmed that WRKY70 specifically activated the transcriptional activity of the prePhHB promoter （Pro-prePhHB）. ConclusionHB is mainly accumulated in the phloem of P. heterophylla tuberous roots. WRKY70 positively regulates HB biosynthesis by directly activating the promoter activity of prePhHB. This study clarifies the key role of WRKY70 in the regulation of HB biosynthesis and provides an important theoretical basis for the in-depth analysis of the molecular regulatory mechanism underlying HB biosynthesis.

ObjectiveTo investigate the association between serum fasting triglyceride glucose-body mass index （TyG-BMI） and new-onset metabolic dysfunction-associated fatty liver disease （MAFLD） within 10 years. MethodsA retrospective analysis was performed for the data of individuals who underwent physical examination in The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University in 2013， 2018， and 2023 and were not diagnosed with MAFLD in 2013， and a total of 1 340 valid subjects were enrolled according to the inclusion and exclusion criteria. The gbmt package in R 4.3.0 was used to construct the dynamic change trajectory model of TyG-BMI， and four different TyG-BMI trajectory groups were determined， i.e.， the low-level group （n=352）， the medium-level group （n=517）， the high-level group （n=314）， and the extremely high-level group （n=157）. The data on general information and blood biochemical parameters were collected from all subjects and were then compared between groups. The chi-square test was used for comparison of categorical data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data with heterogeneity of variance between multiple groups. The Cox regression analysis was used to investigate the association between different TyG-BMI trajectories and the risk of MAFLD， and the receiver operating characteristic （ROC） curve was used to assess the value of TyG-BMI in the diagnosis of MAFLD. ResultsThe cumulative incidence rate of MAFLD increased with the increase in the level of TyG-BMI trajectory， with a cumulative incidence rate of 4.83% in the low-level group， 29.98% in the medium-level group， 61.15% in the high-level group， and 83.44% in the extremely high-level group （P<0.001）， and the cumulative incidence rate of MAFLD in men was significantly higher than that in women （51.34% vs 20.67%， P<0.001）. The multivariate Cox regression analysis showed that increases in the levels of TyG-BMI trajectory， uric acid， diastolic blood pressure， hemoglobin， and alanine aminotransferase were independent risk factors for the onset of MAFLD （all P<0.05）， while the increase in high-density lipoprotein cholesterol was an independent protective factor against MAFLD （P<0.001）. After adjustment for confounding factors， the medium-， high-， and extremely high-level groups had a hazard ratio of 4.430 （95% confidence interval ［CI］： 2.660 — 7.377， P<0.001）， 6.937 （95%CI： 4.110 — 11.708， P<0.001）， and 7.989 （95%CI： 4.616 — 13.827， P<0.001）， respectively. The ROC curve analysis showed that TyG-BMI had the highest diagnostic value， with an area under the ROC curve of 0.859 （95%CI： 0.840 — 0.879）， a sensitivity of 79.8%， and a specificity of 76.3%. ConclusionThe risk of MAFLD increases with the increase in the level of TyG-BMI trajectory， and TyG-BMI can be used as a predictive indicator for MAFLD.

High-throughput sequencing-based high-throughput screening （HTS²） technology， as a new advancement in the field of high-throughput biotechnology， is the world's first technology to integrate high-throughput sequencing into large-scale drug screening and target discovery. The artificially designed DNA probes were bound to the undetermined mRNAs of thousands of genes in cell lysates， and then the probes were ligated with ligases. The large-scale simultaneous detection of gene expression changes in thousands of drug-treated cell samples was performed using barcoding， automated operating platforms， and high-throughput sequencers. This technology enables high-throughput identification of drugs that significantly perturb the gene expression profiles characteristic of diseases. It can also take gene expression signature as the readout and exert great high-throughput advantages in the screening of multi-drug， multi-component， and multi-target drugs， as well as the research on complex mechanisms. Therefore， it is particularly suitable for elucidating the multi-target mechanisms of traditional Chinese medicine and identifying its multi-effective components. Its main technical advantages include high throughput， automation， and low cost. In recent years， HTS² technology has yielded important achievements in the elucidation of the mechanism of action of traditional Chinese medicine formulas， the scientific connotation analysis of the regional characteristics of traditional Chinese medicine， the targeted isolation of active compounds of traditional Chinese medicine， and the discovery of novel pharmacological functions of monomeric compounds of traditional Chinese medicine. In the era of artificial intelligence， HTS² technology will serve as a powerful tool for generating high-quality， original big data of traditional Chinese medicine， providing core data support and promoting AI-driven traditional Chinese medicine research. Ultimately， HTS² technology offers new strategies and critical data support for deeply analyzing the scientific connotation of traditional Chinese medicine and discovering novel traditional Chinese medicine-based drugs， thereby accelerating the modernization and internationalization of traditional Chinese medicine in China.

Curzerene, a sesquiterpene compound isolated from Curcuma Radix, exhibits various therapeutic effects, such as anti-tumor and anti-hyperlipidemic properties. However, its neuroprotective effects have not yet been reported. This study focused on exploring the neuroprotective effect of curzerene and elucidating its potential mechanism by combining molecular biotechnology with multi-omics approaches. Curzerene was orally administered to LPS-induced depressive-like behaviors and cognitive impairment in mice for 14 days, and the related biochemical parameters were evaluated. The possible mechanisms were elucidated using qRT-PCR, Western Blot, immunofluorescence, untargeted metabolomics, GC-MS and 16S rDNA comprehensively. Curzerene ameliorated depression symptoms and cognitive impairment by increasing the preference for sucrose in SPT and the central area and total distance traveled in OFT, reducing the immobility time in TST and FST, as well as rising the spontaneous alternation ratio in Y maze. Multiple molecular biology techniques analyses indicated the ameliorative effect of curzerene via HMGB1/RAGE/ TLR4 pathway. Moreover, curzerene primarily regulates purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, pyrimidine metabolism, etc. Furthermore, intervention increased the relative abundance of Parabacteroides, Clostridia_UCG-014_unclassified, and Rhodospirillales_unclassified, and enhanced the production of SCFAs. This work demonstrated that curzerene effectively protects against LPS-induced neurological damage, potentially by inhibiting the HMGB1/ RAGE/TLR4 pathway through the restoration of gut microbiota homeostasis, modulation of metabolites, and enhancement of SCFAs. In conclusion, this study offers new perspectives on the therapeutic possibilities of curzerene in mitigating depressive-like behaviors and cognitive impairment.

To summarize the clinical characteristics and genetic mutation spectrum of patients with SELENON-related myopathy(SELENON-RM), in order to improve awareness among physicians.

Objective To study carbapenem-resistant Enterobacterales(CRE)infection in the neurosurgical inten-sive care unit(NS-ICU)under the combination of active screening using anal swabs and bundled intervention mea-sures in environment with high prevalence of CRE infection,and provide scientific basis for healthcare-associated in-fection(HAI)prevention and control.Methods Inpatients in NS-ICU from 2020 to 2021 were selected as the con-trol group,and didn't undergo active anal swab screening.NS-ICU inpatients from 2022 to 2023 were taken as the trial group,and implemented intervention of active anal swab screening.Isolation measures for CRE positive cases in two groups were implemented,and the incidence of CRE HAI between two groups of patients were compared.Results 645 patients were actively screened for CRE,with a total of 912 screenings.The overall screening positive rate was 9.21％,and the rectal CRE colonization rate in NS-ICU patients was 13.02％(84/645),out of which Klebsiella pneumoniae accounted for 92.86％(n=78 strains).The positive screening rates in patients in the trial group within 48 hours after admission as well as on day 3-7,day 8-15,and 16-30 were 3.30％,4.94％,13.68％,and 18.85％,respectively.With prolonged hospitalization time,the positive rate of CRE anal swab screening gradually increased.During the study period,the overall CRE HAI rate was 6.24％(72/1 153).After implementing active screening intervention,the CRE HAI rate in the trial group was lower than that in the control group(3.57％[23/645]vs 9.65％[49/508],P＜0.001).Conclusion In hospital environment with high CRE prevalence,implementing active screening and bundled intervention measures can effectively identify CRE carriers and reduce the risk of infection caused by intestinal colonization.

Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

Objective:To explore the correlation between the elevation of glycated hemoglobin A1c (HbA1c) in the first trimester and its change from the first to the second trimester and adverse pregnancy outcomes.Methods:This was a bidirectional cohort study. Singleton pregnant women who delivered in the First Affiliated Hospital, Sun Yat-sen University from March 1, 2021, to July 31, 2024, and had HbA1c results in the first and second trimesters were included. Those with HbA1c<5.7% in the first trimester were described as group E1, and those with HbA1c between 5.7% and 6.4% were described as group E2. Those with HbA1c<5.2% in the second trimester were described as group S1, and those with HbA1c between 5.2% and 6.4% were described as group S2. Accordingly, the changing trend of HbA1c from the first to the second trimester was divided into group E1-S1, group E1-S2, group E2-S1, and group E2-S2. Clinical indicators such as gestational diabetes mellitus (GDM), preeclampsia, preterm birth, preterm premature rupture of membranes (PPROM), polyhydramnios, large for gestational age infants, small for gestational age infants, neonatal hypoglycemia, and neonatal transfer were collected. Comparisons between groups were performed using t-tests, analysis of variance, Mann-Whitney U tests, Kruskal-Wallis tests, Chi square tests, and Fisher's exact test. Multivariate logistic regression analysis was used to analyze the impact of HbA1c in the first trimester and the changing trend of HbA1c from the first to the second trimester on pregnancy outcomes. Results:During the study period, a total of 6 500 pregnant women were included for analysis, among which 209 (3.2%) had HbA1c between 5.7% and 6.4% in the first trimester. Taking those with HbA1c<5.7% as a reference, HbA1c between 5.7% and 6.4% in the first trimester was an independent risk factor for GDM, preterm birth, and PPROM [ OR (95% CI) were 3.304 (2.465-4.427), 1.545 (1.008-2.368), and 1.872 (1.042-3.361), respectively]. Taking group E1-S1 as a reference, HbA1c<5.7% in the first trimester and 5.2%-6.4% in the second trimester (group E1-S2) was an independent risk factor for GDM, preterm birth, PPROM, and neonatal hypoglycemia [ OR (95% CI) were 2.770 (2.370-3.237), 1.424 (1.132-1.791), 1.614 (1.179-2.211), and 2.047 (1.024-4.092), respectively]; HbA1c between 5.7% and 6.4% in the first trimester and<5.2% in the second trimester (group E2-S1) was an independent risk factor for PPROM [ OR (95% CI) was 3.408 (1.187-9.784)]; HbA1c between 5.7% and 6.4% in the first trimester and 5.2%-6.4% in the second trimester (group E2-S2) was an independent risk factor for GDM and preterm birth [ OR (95% CI) were 4.651 (3.282-6.592) and 1.724 (1.066-2.786), respectively]. Conclusions:HbA1c between 5.7% and 6.4% in the first trimester was significantly associated with an increased risk of GDM, preterm birth, and PPROM. For those with HbA1c between 5.7% and 6.4% in the first trimester, if the HbA1c level decreased in the second trimester, only the risk of PPROM increased significantly; conversely, if the HbA1c level continued to increase in the second trimester, the risks of GDM and preterm birth both increased significantly.

Objective:To investigate the characteristics of visual and auditory sustained attention and sex differences in pupils of different grades.Method:Totally 231 students from grades 1 to 6 participated in this stud-y.The development and sex differences of sustained attention were measured by average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates in visual and auditory two-choice re-action time(CRT)tasks.Result:The students in grade 5 had significantly slower visual average reaction times and coefficients of variation for reaction times(P＜0.001 or P＜0.05)than those in grade 3.The students in grade 5 had significantly lower auditory average reaction times,coefficients of variation for reaction times,omission error rates and commission error rates(P＜0.001 or P＜0.01)than those in grade 1.There was no significant sex differ-ences in visual or auditory average reaction times,coefficients of variation for reaction times or omission error rates(Ps＞0.05).Conclusion:There would be age differences in characteristics of both visual and auditory sustained at-tention in pupils,and may be no sex difference in visual or auditory sustained attention.

Objective This is to develop a comprehensive performance evaluation index system for physicians under the DRG system and to conduct practical research.Methods The"cost ratio"is used to establish a"sharing coefficient"to define the distribution of performance among physicians treating the same patient;the Delphi technique is applied to ascertain the weights of evalation index,and the weighted comprehensive index method is utilized to construct the performance evaluation index system for DRG physicians;empirical research on physician performance evaluation is conducted using hospital data.Results Following performance sharing and weighted integration,the basic evaluation indicators and the performance evaluation index of DRG both exhibit an approximate normal distribution between 0～100 points;the performance evalation index of DRG score can be utilized for the overall assessment of physicians,and the strengths and weaknesses of physician diagnosis and treatment can be analyzed based on various dimensional indices and scores.The performance sharing of the evaluation results of the same physician is more accurate than the traditional method,especially for the physicians with more transferred patients.Conclusion Using the"allocation coefficient"to divide the weight of"one patient and multiple doctors"and incorporating the weight into the comprehensive evaluation index system make the results more objective and accurate.The comprehensive performance evaluation index system for DRG physicians,based on the"sharing coefficient"and weighted comprehensive index method,offers a scientific and practical tool for hospital performance distribution management.