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 provide guidance for pharmaceutical care in patients with severe Cryptococcus gattii infections.METHODS Clinical pharmacists participated in the diagnosis and treatment of a male patient with disseminated Cryptococcus gattii infection （involving the lungs and central nervous system）. Given the patient’s poor response to initial therapy， the clinical pharmacists， based on antimicrobial susceptibility test results， recommended voriconazole as an alternative azole. In response to refractory hypokalemia caused by liposomal amphotericin B， the clinical pharmacists assisted the physician in developing an intensive potassium replacement regimen. Regarding the interaction between voriconazole and nifedipine， the clinical pharmacists proactively identified the risk and intensified monitoring of the patient’s blood pressure. In response to the onset of hepatitis C during treatment， the clinical pharmacists thoroughly weighed the priority of infection treatment and recommended temporarily postponing antiviral therapy for hepatitis C. For the individualized use of voriconazole， the clinical pharmacists repeatedly performed therapeutic drug monitoring （TDM）. Regarding the patient’s poor lesion resolution， the clinical pharmacists participated in multidisciplinary team discussions to clarify the indications for surgery.RESULTS The physician adopted the clinical pharmacists’ recommendations. Following pharmacological treatment and surgical intervention， the patient’s condition stabilized， and he was discharged while still on medication.CONCLUSIONS For severe Cryptococcus gattii infections， clinical pharmacists should focus on pathogen characteristics， strengthen adverse reaction management， pay close attention to drug interactions， conduct TDM， and actively participate in multidisciplinary team collaboration to ensure the safety and efficacy of patient treatment.

The Hazardous Drug Exposure Management: Information for Healthcare Settings (2023 Edition) released by the National Institute for Occupational Safety and Health (NIOSH) of US provided detailed protection recommendations for medical personnel to mitigate the risks of occupational exposure to hazardous drugs. This study reviewed the literature in terms of hazard identification, occupational exposure assessment, risk assessment, risk management planning, and waste and spill control. It also explored the precautions for each step of hazardous drug handling, aiming to raise medical personnel's awareness of hazardous drug protection and improve their self-protection skills. The findings provided valuable references for medical institutions to develop hazardous drug disposal plans and reduce employees' exposure to hazardous drugs and occupational injuries.

Objective To explore the cost effectiveness of osimertinib and gefitinib in the treatment of advanced non-small cell lung cancer （NSCLC） with epidermal growth factor receptor （EGFR） mutation. Methods A total of 52 advanced NSCLC patients with EGFR mutation treated by osimertinib were selected as group A from June 2021 to August 2022 at the Chengde Central Hospital, and 52 patients treated by gefitinib were selected as group B according to the propensity score matching method in 1∶1 ratio. The treatment cost and effect of the two groups of patients were compared, and the cost-effectiveness ratio was calculated, and sensitivity analysis was conducted. Results The total effective rate of group A was higher than that of group B （90.38% vs 71.15%, χ²=6.190, P=0.013）. The drug cost and total treatment cost of group A were higher than those of group B（P<0.05）, and other direct costs were lower than those of group B （P<0.05）. The incremental cost effectiveness ratio of group A was 374.71. After the cost-effectiveness sensitivity analysis on adjusting drug costs to decrease by 10% and the total effective rate to decrease by 10% of the two groups, the sensitivity analysis results were basically consistent with the original results. Conclusion Based on the latest prices and actual case data of osimertinib and gefitinib, osimertinib was better than gefitinib in the treatment of advanced NSCLC patients with EGFR mutation. Although gefitinib had lower treatment costs, osimertinib had more cost effectiveness advantages. These findings could provide important reference for the clinical development of treatment plans for advanced NSCLC patients with EGFR mutations.

Objective:To investigate renal impairment and ferroptosis due to severe blast injuries and related mechanism.Methods:The goats were placed 3 meters away from the center of an 8 kg TNT-equivalent explosive to carry out blast injury experiments.The physical parameters of blast waves were measured,and the pathological severity of blast injuries was graded and scored to assess the severity of injuries.Vital signs,blood gas parameters,and renal function markers were measured before injury and at 1,3,6,and 24 hours after injury.Renal tissue samples were collected at 24 hours after injury to prepare tissue sections,which were used to perform HE staining and measure the changes in the content of Fe2+and the expression of the ferroptosis-related marker proteins xCT and GPX4 in renal tissue,and Prussian blue staining was performed for renal tissue sections to investigate the mechanism associated with renal impairment and ferroptosis of renal cells.Results:Severe blast injuries accounted for the highest proportion of 47.2%in experi-mental goats,while mild,moderate,severe,and extremely severe injuries accounted for 2.8%,36.1%,47.2%,and 13.9%,respectively,and the pathologic severity score of blast injury was 2.56±0.15.For the goats after blast injury,there were significant increases in heart rate(F=12.750,P<0.01)and respiratory rate(F=6.500,P<0.01)and significant reductions in anal temperature(F=3.496,P<0.05),partial pressure of blood oxygen(F=24.630,P<0.01),and blood oxygen saturation(F=18.560,P<0.01),as well as significant increases in the levels of blood uric acid(F=22.320,P<0.01),serum creatinine(F=15.350,P<0.01),and blood urea nitrogen(F=22.310,P<0.01).Compared with the control group,swelling of renal tubular epithelial cells and narrowing of tubular lumen were observed at 24 hours after blast injury,with a significant increase in the content of Fe2+in renal tissue(t=5.933,P<0.01),significant reductions in the relative expression protein levels of GPX4(t=7.924,P<0.01)and xCT(t=4.483,P<0.01)in renal tissue,and deposi-tion of a large amount of iron ions in renal tubular epithelial cells.Conclusion:Experimental goats placed 3 meters away from the cen-ter of an 8 kg TNT-equivalent explosive can cause severe blast inju-ries,resulting in the onset of hypoxia,renal impairment,and ferrop-tosis of renal tubular epithelial cells.

Objective: To explore the clinical and imaging characteristics of patients with regional odontodysplasia accompanied by hypodontia and to provide a reference for clinical diagnosis and treatment. Methods: This report presents the imaging manifestations, diagnosis, and treatment of a case of regional odontodysplasia (RO) accompanied by hypodontia. It includes a retrospective summary of the dynamic changes in the imaging characteristics of the affected teeth over a 5-year period, along with a comparative analysis of the literature. The patient was a 9-year-old female who presented to the Clinic of Oral Rare and Genetic Diseases of our hospital with the chief complaint of “discomfort for over seven months following the extraction of the teeth in the left mandibular region.” Based on her clinical manifestations and imaging findings, she was diagnosed with RO in the left mandible and with hypodontia of permanent teeth 12 and 34. A treatment plan was formulated, and long-term follow-up was conducted. The current radiographic images were compared with previous imaging data to summarize the developmental changes in her teeth, and a comparative analysis was also performed with the literature to identify similarities and differences with previously reported RO dental characteristics. Results: During the follow-up period, the patient's symptoms did not worsen, and a conservative observation approach was adopted; the treatment plan was decided after the eruption of the affected teeth. By comparing and analyzing imaging data from three ages (4.5, 8.5, and 9 years old), it was determined that the deciduous and permanent teeth in the left mandible of this patient exhibited typical “ghost” radiographic features, alongside hypodontia of teeth 12 and 34, as well as the delayed development of tooth 35. A literature review and analysis indicated that RO manifests clinical characteristics such as delayed tooth eruption, reduced tooth size, and yellow crowns, along with typical “ghost” radiographic appearances. Treatment requires a personalized approach based on the patient’s specific condition. To date, only five cases of RO patients with hypodontia have been reported, while the delayed development of permanent tooth buds has not yet been documented. Conclusion For patients with RO, dynamic imaging evaluation plays a critical role in early diagnosis. RO is associated with hypodontia and delayed tooth germ development. Long-term follow-up and personalized treatment plans are the key to RO treatment.