Discoidin domain receptor 1(DDR1)is overexpressed in various tumors,such as triple-negative breast cancer(TNBC),and is rarely expressed in normal tissues.These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate(ADC)for targeted therapy.Here,we investigated the preparation and preclinical efficacy of DDR1-DX8951,an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly(GGFG)linker.The anti-DDR1 monoclonal antibody was coupled to DX8951(i.e.,DDR1-DX8951),producing the targeted ther-apy ADC.The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models.DDR1-DX8951 can specifically target DDR1,be quickly internal-ized by TNBC cells,and reduce the viability of TNBC cells in vitro.The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models.Importantly,our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvi-ronment(TME)of TNBC.Taken together,this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Discoidin domain receptor 1 (DDR1) is overexpressed in various tumors, such as triple-negative breast cancer (TNBC), and is rarely expressed in normal tissues. These characteristics make DDR1 a preferable target candidate for the construction of an antibody-drug conjugate (ADC) for targeted therapy. Here, we investigated the preparation and preclinical efficacy of DDR1-DX8951, an ADC that includes an anti-DDR1 monoclonal antibody conjugated to DX8951 by a cleavable Gly-Gly-Phe-Gly (GGFG) linker. The anti-DDR1 monoclonal antibody was coupled to DX8951 (i.e., DDR1-DX8951), producing the targeted therapy ADC. The antitumor activities of DDR1-DX8951 monotherapy or DDR1-DX8951 plus pembrolizumab were assessed in TNBC mouse models. DDR1-DX8951 can specifically target DDR1, be quickly internalized by TNBC cells, and reduce the viability of TNBC cells in vitro. The potent antitumor activity of DDR1-DX8951 was revealed in TNBC xenograft models. Importantly, our investigation demonstrated that DDR1-DX8951 plus pembrolizumab not only revealed the inhibitory efficacy on tumor growth and metastasis but also played an important role in improving the immunosuppressive tumor microenvironment (TME) of TNBC. Taken together, this investigation provides justification for large-sample studies to further assess the safety and efficacy of DDR1-DX8951 plus pembrolizumab for TNBC clinical trials.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p(miR-126a-5p)and vascular endothelial growth factor(VEGF)signaling pathway in cervical spondylotic myelopathy model rats.Methods Thirty healthy male SD rats were divided into the sham operation group,the model group and the traditional Chinese medicine(TCM)group by random number table method.Cervical spondylotic myelopathy models were prepared in the model group and the TCM group.The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction,while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks.After intervention,the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests.Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin(HE)staining and observe the number of vascular buds in intervertebral disc.Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining.The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay.Results Compared with the sham operation group,the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group.The cell destruction of intervertebral disc annulus was obvious in rats,and apoptosis was high and cell density decreased.Mechanical stimulation threshold decreased,and mechanical stimulation threshold decreased.The level of miR-126a-5p was decreased,and the expression levels of VEGF mRNA and protein were increased.Compared with the model group,the number of vascular buds in intervertebral disc was increased in the TCM group.The destruction of intervertebral disc annulus cells was alleviated in rats.The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased.The threshold of mechanical stimulation increased,and the retraction time of thermal stimulation was prolonged.The level of miR-126a-5p increased,and the expression levels of VEGF mRNA and protein decreased(P＜0.05).Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.

Objective To compare the bioavailability and bioequivalence of pivastatin calcium dispersive tablets in healthy Chinese subjects.Methods A single dose of pitavastatin calcium(2 mg)was orally administered to the test preparation or reference preparation under fasting and postprandial conditions,respectively.The plasma concentrations of pitavastatin calcium were measured at different time points before and after administration by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The bioequivalence of the two formulations was evaluated.Results Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the Cmax were(47.79±23.99)and(46.03±21.82)ng·L-1;AUC0_,were(96.56±42.64)and(97.96±35.40)ng·h·L-1;AUC0_∞ were(102.09±43.01)and(103.46±35.62)ng·h·L-1,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0_t and AUC0-∞ of pitavastin-calcium test formulation and reference formulation were 96.28％-111.16％,94.46％-101.19％and 94.77％-101.31％,respectively.Subjects received pitavastatin calcium test preparation and reference preparation in fasting condition,the Cmax were(27.32±10.68)and(28.58±11.39)ng·L-1;AUC0_t were(82.76±27.58)and(84.06±29.12)ng·h·L-1;AUC0_∞ were(87.88±26.93)and(89.29±29.18)ng·h·L-1,respectively.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0_t and AUC0_∞ of the test formulation and the reference formulation of pitavastatin calcium were 87.39％-102.10％,94.62％-101.34％and 94.88％-101.47％,respectively.All of them were within the bioequivalence range of 80.00％to 125.00％.Conclusion Two pivastatin calcium dispersion tablets were bioequivalent and safe in healthy Chinese adult subjects.

To comprehensively assess the true visual function of clinical dry eye patients and the comprehensive impact of blinking characteristics on functional vision of the human eye,an intelligent vision measurement system has been designed and developed to detect and analyze blinks from the side.The system employs deep learning keypoint recognition technology to analyze eyelid features from a lateral perspective.It presents the data of identified key points for the upper and lower eyelids in a line chart format and annotates the trough of each blink.By setting benchmark values,the system automatically calculates the proportion of complete and incomplete blinks in the tested individuals.The results indicate that the system is stable in performance and accurate in measurement,successfully achieving the anticipated design objectives.It thereby provides reliable technical support for future clinical applications.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K (1-7), and six new 14-residue peptaibols, harzianins NPDG J-O (8-13). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D (14-17) were also identified. The structural configurations of the newly identified peptaibols (1-13) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey's method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols (1-7, 14-17) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8-32 μg·mL^-1. Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL^-1.
Peptaibols/chemistry* ; Trichoderma/metabolism* ; Tandem Mass Spectrometry/methods* ; Anti-Infective Agents/pharmacology* ; Spectrometry, Mass, Electrospray Ionization/methods*