Objective: To explore the association between mental health status and adverse childhood experiences (ACEs) among sexual minority college students, so as to provide a scientific basis for mental health education and health promotion in universities. Methods: From January to February 2024, convenience and cluster sampling methods were used to select 1 792 college students from 11 colleges in Guangxi. A self reporting method was applied to identify 476 sexual minority individuals. The Symptom Check-List 90 (SCL-90) and the Simplified Chinese Adverse Childhood Experiences International Questionnaire (SC-ACE-IQ) were employed to assess mental health and ACEs. Multivariate Logistic regression analysis was conducted to examine the associations. Results: The detection rates of all psychological issues among sexual minority college students in Guangxi were significantly higher than those of non sexual minority college students ( χ 2=56.01-91.39, all P <0.01). Except for physical neglect, bullying, and community violence, sexual minority students exhibited higher reporting rates of other ACEs types compared to nonsexual minority students ( χ 2= 4.52-13.34, all P <0.05). The total ACEs score for college students was 1.00 (1.00, 2.00), while the SCL-90 total score was 96.00 (113.00, 160.00). Spearman correlation analysis revealed a positive correlation between ACEs total scores and SCL-90 total scores ( r=0.29, P <0.05). Additionally, all ACEs subscales, including emotional neglect, physical neglect, emotional abuse, sexual abuse, parental loss, domestic violence, and community violence were positively correlated with corresponding SCL-90 subscale scores ( r =0.05-0.22, all P <0.05). Multivariate Logistic regression analysis showed that family violence increased the risk of mental health issues for sexual minority students ( OR=1.61, 95%CI =1.26-2.09); emotional neglect ( OR= 1.05 , 95%CI =1.00-1.10), physical neglect ( OR=1.20, 95%CI =1.06-1.35), sexual abuse ( OR=1.49, 95%CI =1.15-1.93) increased mental health risks for non sexual minority students (all P <0.05). The cumulative effects of ACEs were all statistically significant in the total sample and both subgroups (all P <0.05). Conclusion Mental health status among sexual minority college students in Guangxi is associated with ACEs, and their well being requires active attention

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

Aim To study the effects of whole herb of Prunella and its active components on the malignant progression of breast cancer and its mechanism.Meth-ods Breast cancer transplantation tumor model was constructed and randomly divided into the model group,low,medium and high dose group of whole herb of Prunella(0.1,0.2,0.4 g·mL-1 by gavage)and paclitaxel(10 mg·kg-1 by intraperitoneal injection),which was administered by gavage every day,and the tumor tissues were collected after 28 days of interven-tion.The weight,tumor volume and mass of nude mice in each group were detected,HE staining was used to observe the morphology of breast cancer tumor tissues,and immunohistochemical staining was used to observe the proliferation of cell-cycle regulatory protein-67(Ki-67)and cytokeratin 17(CK17)in breast cancer tumor tissues.The cellular experiments were performed by u-sing different concentrations of the ethyl acetate extract of the whole herb of Prunella in breast cancer MDA-MB-231 cells for 24 h.The proliferation of MDA-MB-231 cells and the effects on the cell cycle and apoptosis of MDA-MB-231 cells were detected by using the CCK-8 assay,the cell cycle flow and the apoptotic cell flow.Western blot was used to detect the effect of ethyl ace-tate extract of whole herb of Prunella on the expression of apoptosis-related proteins in breast cancer MDA-MB-231 cells.UPLCQ-TOF MS/MS was used to detect the chemical compositions of the ethyl acetate extract of Prunella whole herb.Results The whole herb of Pru-nella had no significant effect on the growth of nude mice(P＞0.05);it could significantly inhibit the growth of transplanted tumors in nude mice with human breast cancer(P＜0.05);the results of HE staining showed that the cells in the tissues appeared to be rela-tively sparse with the increase of the dose of Prunella and had different degrees of nuclear consolidation and deep staining of nuclei and the apoptosis of the tumor cells increased;the metastasis of tumor cells to the liv-er and lungs was inhibited,when compared with that in the model group.Compared with the model group,the low,medium and high groups of Prunella had no signif-icant effect on the liver index,while the spleen index was significantly reduced(P＜0.05);the expression of Ki-67 and CK17 was reduced.The ethyl acetate ex-tract of the whole herb of Prunella could inhibit the proliferation of MDA-MB-231 cells in breast cancer(P＜0.01);the results of flow cytometry showed that,with the increase of the concentration of the ethyl ace-tate extract of the whole herb of Prunella,the proportion of S-phase cells in the MDA-MB-231 cells significantly increased,and the proportion of G0/G1-phase cells sig-nificantly decreased,while the proportion of G2-phase cells did not change significantly(P＜0.01);Western blotting was not affected in the low,medium and high groups,and the spleen index significantly decreased(P＜0.05);the expression of Ki-67 and CK17 was re-duced;the results of Western blot showed that the eth-yl acetate extract of the whole herb of Prunella promo-ted the expression of Bax,cleaved caspase-3,cleaved caspase-9 proteins,and inhibited the expression of Bcl-2,caspase-3,caspase-9,cyclinA2,and CDK2 proteins(P＜0.05,P＜0.01).The acetic acid of the whole herb of Prunella ethyl ester extract identified a total of 51 compounds.Conclusions The whole herb of Pru-nella can inhibit the growth of breast cancer in nude mice transplanted with tumors,promote the apoptosis of tumor cells,inhibit the proliferation of breast cancer MDA-MB-231 cells,inhibit the metastasis of tumor cells to the liver and lungs,protect the liver and spleen,and reduce the expression of the value-added markers Ki-67 and CK17 in tumor tissues,and the ef-fective ingredient of the whole herb,the ethyl acetate extract,can induce apoptosis.The mechanism may be related to the down-regulation of cyclinsA2,CDK2,Bcl-2,caspase-3,caspase-9 and up-regulation of Bax,cleaved caspase-3,cleaved caspase-9 protein expres-sion.

OBJECTIVE To study the characteristics,micro-traits and microscopic characteristics of Peucedani radix and seven kinds of its common varieties and summarize the key identification characteristics so as to provide a reference for the effective identifica-tion of Peucedani radix and its common varieties.METHODS The key identification features and high-definition images of Peucedani radix and its common varieties were obtained by using the identification methods of traits,microtraits and microscopy,combined with the techniques of depth-of-field extended imaging and image stitching,and some of the features were digitally extracted and statistical-ly analyzed by SPSS26.0 software.RESULTS The high-definition color image data of Peucedani radix and its common varieties were obtained.Its specific identification features were:root head length and annular sparseness,skin pore shape and area,root texture,and fracture surface oil spot density,etc.under the property identification;the diameter and number of oil chambers,the number of cathe-ters,the presence or absence of bast fibers and wood fibers,etc.under the microscopic identification.The results of statistical analysis showed that there were significant differences in skin pore area,oil chamber diameter and density,and conduit density among different varieties of Peucedani radix(P<0.01).CONCLUSION Micro-traits and microidentification methods can be comprehensively ap-plied to distinguish Peucedani radix and its common varieties.In particular,the microscopic features of polarized light holographic col-or images in cross section have significant distinguishing significance,and some of the features are digitally extracted and statistically analyzed,which makes up for the shortcomings of subjective factors in the traditional empirical identification research,and provides a reference for the circulation,testing,clinical medication,and standard drafting of Peucedani radix.

Objective To preliminarily investigate the safety and efficacy of percutaneous microwave ab-lation(MWA)in patients with advanced breast cancer involving the skin or nipple-areola complex(NAC).Methods This study included breast cancer patients with skin or NAC involvement treated at the Fifth Medical Center of the Chinese PLA General Hospital from January 2011 to August 2024.Patients underwent percutaneous MWA with water isolation technique to protect surrounding tissues.Clinical data were retrospectively collected,and the technical success rate,complications,prognosis,patient satisfaction with breast aesthetics,and quality of life improvement were analyzed.Results A total of 19 patients(24 lesions)meeting the inclusion and ex-clusion criteria were analyzed.The cases included 4 with T4N0M0,2 with T4N1M0,3 with T4N2M0,1 with T4N3M0,1 with T4N2M1,and 8 with T4N3M1.The average diameter of the 24 lesions was(4.9±3.4)cm,with an average of(1.6±0.6)ablation sessions per lesion.The median ablation time was 36.9(26.1,61.7)minutes,and the median ablation energy was 84.2(45.6,149.2)kJ.The technical success rate was 100%.Postoperatively,7 patients(7/19,36.8%)experienced skin burns around the lesion or nipple shedding,all of which healed naturally.The median overall survival was 35.0(17.0,45.5)months,and the median recur-rence-free survival was 17.0(11.0,38.5)months.Patient satisfaction with post-treatment breast aesthetics was 89.5%,and all patients reported significant improvement in their quality of life.Conclusions Percutane-ous microwave ablation for breast cancer involving the skin or NAC was preliminary demonstrates to be safe and effective,suggesting its potential as a viable treatment option for patients with inoperable breast cancer.