Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

Purpose To evaluate the diagnostic accuracy of low-iodine contrast subtraction CT pulmonary angiography(CTPA)combined with iodine maps for acute pulmonary embolism(APE),with a focus on detecting subsegmental emboli.Materials and Methods A retrospective analysis included 48 patients with suspected APE who underwent both pulmonary ventilation/perfusion SPECT/CT and low-iodine subtraction CTPA within one week in Beijing Hospital from September 1,2021 to September 1,2024.Using SPECT/CT as the reference standard,the diagnostic performance of subtraction CTPA with iodine maps was assessed.A retrospective review was performed to identify potential causes of false-positive and false-negative results.Results Subtraction CTPA with iodine maps demonstrated high diagnostic accuracy at the segmental and subsegmental pulmonary artery levels,with a sensitivity of 0.917 and specificity of 0.991.At the segmental level,the detection rate was 100%,while at the subsegmental level,it was 66.7%.The method showed consistently high diagnostic performance(83.3%-100%)across different clinical risk stratifications of APE.Retrospective review identified explicable causes for 85.7%(6/7)of false-positive and 33.3%(2/6)of false-negative cases.Conclusion Low-iodine subtraction CTPA combined with iodine maps exhibits robust diagnostic efficacy for APE.Accurate recognition of characteristic perfusion defects on iodine maps may further enhance diagnostic precision.

OBJECTIVE To carry out regular monitoring of carbapenem-resistant Klebsiella pneumoniae(CRKP)contamination status in the environment of intensive care unit(ICU)and take targeted prevention and control measures so as to reduce the incidence of hospital-associated infections with multidrug-resistant organisms(MDROs).METHODS The surfaces of surroundings of the patients who were colonized and infected with CRKP in the ICU of grade A tertiary hospital of Shanghai and the hands of relevant staff were sampled by stages from Jan 1,2021 to Jun 30,2024.The distribution of the CRKP strains in the surroundings were analyzed according to the locations positive for CRKP,and the disinfection measures were accordingly and continuously modified.The trend of isolation rate of CRKP strains from the ICU patients was analyzed during the time period when the measures were implemented.RESULTS Totally 266 environmental samples were collected during the baseline period(from Jan.1 2021 to Dec.31 2021),265 during intervention period(from Jan.1 2022 to Dec.31 2023),274 during con-solidation period(from Jan.1 to Jun.30 2024);the isolation rates of the CRKP strains were 4.51％,4.91％and 3.65％,respectively.The isolation rate of the strains was highest from the bed unit(10.40％),followed by the article for public use(6.74％),articles used by health care workers(2.98％)and diagnosis and treatment arti-cles(1.91％).The isolation rate of CRKP of the patients was 24.75％during the baseline period,15.48％during the intervention period,5.69％during the consolidation period,showing a continuously downward trend(x2=30.330,P＜0.001).CONCLUSION It is necessary to regularly carry out the environmental monitoring of CRKP strains,seek for the weak links of environmental disinfection and implement the intensified prevention and control measures so as to reduce the incidence of CRKP infection,which may provide theoretical bases for effective control of the CRKP strains.

Purpose To evaluate the diagnostic accuracy of low-iodine contrast subtraction CT pulmonary angiography(CTPA)combined with iodine maps for acute pulmonary embolism(APE),with a focus on detecting subsegmental emboli.Materials and Methods A retrospective analysis included 48 patients with suspected APE who underwent both pulmonary ventilation/perfusion SPECT/CT and low-iodine subtraction CTPA within one week in Beijing Hospital from September 1,2021 to September 1,2024.Using SPECT/CT as the reference standard,the diagnostic performance of subtraction CTPA with iodine maps was assessed.A retrospective review was performed to identify potential causes of false-positive and false-negative results.Results Subtraction CTPA with iodine maps demonstrated high diagnostic accuracy at the segmental and subsegmental pulmonary artery levels,with a sensitivity of 0.917 and specificity of 0.991.At the segmental level,the detection rate was 100%,while at the subsegmental level,it was 66.7%.The method showed consistently high diagnostic performance(83.3%-100%)across different clinical risk stratifications of APE.Retrospective review identified explicable causes for 85.7%(6/7)of false-positive and 33.3%(2/6)of false-negative cases.Conclusion Low-iodine subtraction CTPA combined with iodine maps exhibits robust diagnostic efficacy for APE.Accurate recognition of characteristic perfusion defects on iodine maps may further enhance diagnostic precision.

OBJECTIVE To carry out regular monitoring of carbapenem-resistant Klebsiella pneumoniae(CRKP)contamination status in the environment of intensive care unit(ICU)and take targeted prevention and control measures so as to reduce the incidence of hospital-associated infections with multidrug-resistant organisms(MDROs).METHODS The surfaces of surroundings of the patients who were colonized and infected with CRKP in the ICU of grade A tertiary hospital of Shanghai and the hands of relevant staff were sampled by stages from Jan 1,2021 to Jun 30,2024.The distribution of the CRKP strains in the surroundings were analyzed according to the locations positive for CRKP,and the disinfection measures were accordingly and continuously modified.The trend of isolation rate of CRKP strains from the ICU patients was analyzed during the time period when the measures were implemented.RESULTS Totally 266 environmental samples were collected during the baseline period(from Jan.1 2021 to Dec.31 2021),265 during intervention period(from Jan.1 2022 to Dec.31 2023),274 during con-solidation period(from Jan.1 to Jun.30 2024);the isolation rates of the CRKP strains were 4.51％,4.91％and 3.65％,respectively.The isolation rate of the strains was highest from the bed unit(10.40％),followed by the article for public use(6.74％),articles used by health care workers(2.98％)and diagnosis and treatment arti-cles(1.91％).The isolation rate of CRKP of the patients was 24.75％during the baseline period,15.48％during the intervention period,5.69％during the consolidation period,showing a continuously downward trend(x2=30.330,P＜0.001).CONCLUSION It is necessary to regularly carry out the environmental monitoring of CRKP strains,seek for the weak links of environmental disinfection and implement the intensified prevention and control measures so as to reduce the incidence of CRKP infection,which may provide theoretical bases for effective control of the CRKP strains.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

OBJECTIVE: Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. RESULTS: PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. CONCLUSION Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

OBJECTIVE: Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. RESULTS: PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. CONCLUSION Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

OBJECTIVE: Surgical wounds that can’t complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing.APPROACH: The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. RESULTS: PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate [ 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells.INNOVATION: Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. CONCLUSION Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.