OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

Objective: To evaluate the suitability of the existing hemolysis rate standards for locally processed red blood cell components by retrospectively analyzing 5-year hemolysis rate data at the end of storage. Methods: A total of 720 blood samples of three types of red blood cell components from our blood station from January 2019 to December 2023 were collected. Parameters included hemoglobin concentration (Hb), hematocrit (Hct), and free hemoglobin concentration (fHb). Hemolysis rate were taken as the control standard of 0.8% in accordance with the national standard. The hemolysis rates were compared against the national standard threshold of 0.8% (GB18469-2012), and annual trends of the detection parameters were observed. Results: The hemolysis rates (x-+s,%) of leukocyte-depleted whole blood at the end of storage were (0.038±0.023 8) in 2019, (0.049±0.039 5) in 2020, (0.043±0.040 7) in 2021, (0.049±0.030 7) in 2022, and (0.058±0.054 8) in 2023, respectively; The hemolysis rates (x-+s" />,%) of leukocyte-depleted suspended red blood cells at the end of storage were (0.093±0.050 2) in 2019, (0.086±0.049 5) in 2020, (0.123±0.072 3) in 2021, (0.122±0.052 1) in 2022, and (0.106±0.058 6) in 2023, respectively; The hemolysis rates (x-+s,%) of washed red blood cells at the end of storage were (0.127±0.038 2) in 2019, (0.150±0.066 5) in 2020, (0.121±0.052 2) in 2021, (0.124±0.038 9) in 2022, and (0.128±0.044 3) in 2023, respectively. Conclusion: Hemolysis rates at the end of blood storage of three red blood cell components were significantly lower than the limits specified in Quality Requirements for Whole Blood and Components (GB18469-2012), as well as standards from the EU, AABB and the United States. The results demonstrate excellent product quality control. A regional internal control standard of <0.2% is proposed for hemolysis rates at the end of storage.

Radiotherapy is main method in treating cervical cancer,and the rapid advancement of artificial intelligence(AI)technique is providing entirely new solutions for radiotherapy for cervical cancer.The AI means that is represented by deep learning is deeply integrating into the whole process of diagnosis,treatment and management for cervical cancer,which can promote intelligent and precise development of radiotherapy workflows.Currently,the applied cores of AI in radiotherapy for cervical cancer include image registration,target delineation,optimization of radiotherapy planning and risk assessment,which can significantly enhance efficiency and precision of treatment.But,AI is facing some challenges in clinical applications include data quality,and algorithm's robustness and interpretability at the same time.Depended on the above analyses,this paper systematically reviewed the frontier applications and progress in practice of AI in radiotherapy for cervical cancer,which especially analyzed technical advantages and limitations of AI in key link,and explored its development path and coping strategy in clinical promotion and standard application in future.It is purpose to provide theoretical references for clinical practice of precise and accurate radiotherapy for cervical cancer.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

Objective To explore the clinical value of high frequency ultrasound combined with dermoscopy in preoperative evaluation of cutaneous malignant tumors.Methods A total of 323 patients with suspected cutaneous malignant tumors were selected from Jinhua Municipal Central Hospital from January 2022 to December 2023.The clinical value of high frequency ultrasound,dermoscopy and their combined examination in preoperative diagnosis of cutaneous malignant tumors were analyzed and compared.Results A total of 323 patients with suspected cutaneous malignant tumors,223 patients with confirmed cutaneous malignant tumors by skin pathology,234 skin lesions,and 100 patients with benign skin tumors were included.141 skin lesions were detected by dermoscopy,195 skin lesions by high frequency ultrasound,and 213 skin lesions by the combination of dermoscopy and high frequency ultrasound.The sensitivity,specificity and accuracy of high frequency ultrasound combined with dermoscopy in diagnosis of cutaneous malignant tumors were 87.6％,92.0％and 88.9％,respectively,which was higher than that of single high frequency ultrasound and single dermoscopy.The diagnosis results of dermoscopy combined with high frequency ultrasound were in good agreement with the pathological results(kappa=0.75).Conclusion Dermoscopy and high frequency ultrasound are convenient,non-invasive and sensitive imaging methods for skin detection.They can balance resolution and depth of detection,reveal morphological information of tumors,and predict the risk of tumor recurrence.

Radiotherapy is main method in treating cervical cancer,and the rapid advancement of artificial intelligence(AI)technique is providing entirely new solutions for radiotherapy for cervical cancer.The AI means that is represented by deep learning is deeply integrating into the whole process of diagnosis,treatment and management for cervical cancer,which can promote intelligent and precise development of radiotherapy workflows.Currently,the applied cores of AI in radiotherapy for cervical cancer include image registration,target delineation,optimization of radiotherapy planning and risk assessment,which can significantly enhance efficiency and precision of treatment.But,AI is facing some challenges in clinical applications include data quality,and algorithm's robustness and interpretability at the same time.Depended on the above analyses,this paper systematically reviewed the frontier applications and progress in practice of AI in radiotherapy for cervical cancer,which especially analyzed technical advantages and limitations of AI in key link,and explored its development path and coping strategy in clinical promotion and standard application in future.It is purpose to provide theoretical references for clinical practice of precise and accurate radiotherapy for cervical cancer.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Objective To explore the correlations of serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) with grading of myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPN). Methods Ninety patients with Philadelphia chromosome negative (Ph-)MPN were selected as MPN group. According to the grading criteria for myelofibrosis by the World Health Organization (WHO) in 2016, MPN patients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases; another 50 healthy volunteers were selected as the control group. Levels of serum VEGF, MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay, and the ratio of TIMP-1 to MMP-9 (TIMP-1/MMP-9) was calculated. Spearman rank correlation test was used to analyze the correlations of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 with MF grading. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of each indicator alone or their combination for diagnosing MPN or distinguishing MF grading. Results Compared with the control group, the serum levels of VEGF, MMP-9 and TIMP-1 in the MPN group increased significantly (P < 0.05). Values of area under the curve (AUC) of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0, 834, 0.745, 0.923 and 0.618 respectively; the AUC of the combined diagnosis of MPN by VEGF, MMP-9 and TIMP-1 was 0.960; when the optimal cut-off value was 0.627, the sensitivity was 85.56%, and the specificity was 92.00%. Compared with the pre-fibrosis or early fibrosis group, the serum levels of VEGF, TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly (P < 0.05). Spearman correlation analysis showed that VEGF (r=0.378, P=0.001), TIMP-1 (r=0.512, P < 0.001) and TIMP-1/MMP-9 (r=0.353, P=0.001) were positively correlated with the MF grading of MPN patients (P < 0.05). ROC curve analysis showed that the values of AUC of VEGF, MMP-9, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723, 0.523, 0.802 and 0.708 respectively; the AUC of the combined detection of VEGF, TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838; when the optimal cut-off value was 0.530, the sensitivity was 72.22%, and the specificity was 85.19%. Conclusion Serum VEGF, TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients, and the combined detection of these indicators can predict the MF degree of MPN patients.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

【Objective】 To evaluate the quality of platelet concentrates (PCs) prepared by traditional and modified buffy coat centrifugal canning methods, and to explore the effect of modified buffy coat centrifugal canning method on improving the quality of PCs. 【Methods】 The buffy coat centrifugal canning methods was divided into traditional group and modified group. In the traditional group, the buffy coat component bag and empty bag were directly combined layer by layer and vertically canned for light centrifugation. In the modified group, a foam spacer was added between the buffy coat component bag and the empty bag for light centrifugation layer by layer. The effects of the two groups of centrifugal canning methods on the preparation quality of PCs were observed. 【Results】 The platelet content in PCs prepared by the modified buffy coat centrifugal canning method was significantly higher than that in the traditional group, and the mixed amount of red blood cells was lower than that in the traditional group (P<0.05). Although there was no statistically significant difference in the qualified rate of platelet content between the two groups (P>0.05), the qualified rates of platelet content and mixed red blood cell in the modified group were higher than those in the traditional group (P<0.05). 【Conclusion】 The modified centrifugal canning method with buffy coat can improve the quality of PCs, which is convenient and cheap, and is worth popularizing.