Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) comprise a group of clonal disorders originating from hematopoietic stem cells, commonly characterized by thrombotic events, extramedullary hematopoiesis, and a propensity for malignant progression to myelofibrosis or acute leukemia. With the inclusion in the core diagnostic criteria, molecular biomarkers has exhibited applicational valus in multiple levels in the aspects of personalized therapy to subtype MPN, interpret phenotypic heterogeneity, and predict clinical outcomes. Molecular biomarkers are currently being applied in disease diagnosis, progression prediction, therapeutic strategy refinement, precision monitoring, familial MPN screening, and the development of emerging detection technologies, advancing the shift from fundamental MPN research to individualized clinical management.

Objective:To explore a new surgical approach [anteromedial approach of the hip (AMA)] for Pipkin Ⅰ and Ⅱ femoral head fractures through an imaging and anatomical study.Methods:The hip imaging data were collected of the 38 patients who had undergone lower limb CT angiography for open tibiofibular fractures at Department of Orthopaedics, The Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University from June 2023 to January 2024. There were 20 males aged (40.9±3.5) years and 18 females aged (41.5±3.3) years. The origins and shapes of the femoral artery and its main branches were observed. The distances between the femoral head and the femoral artery, the medial femoral circumflex artery, and the lateral femoral circumflex artery were measured. Four fresh adult cadavers were collected, including 2 males and 2 females. Their ages of death were 56, 65, 72 and 78 years old, respectively. An incision was made along the axis of the limb at the midpoint of the inguinal ligament at the 4 fresh cadavers. After the femoral head was exposed through the gap between the femoral artery and the femoral nerve, the range of the femoral head exposed was marked.Results:The femoral artery ran along the anteromedial side of the femoral head. The shortest distance between the medial femoral circumflex artery and the femoral head was (13.1±5.7) mm, and the shortest distance between the origin of the lateral femoral circumflex artery and the femoral head (21.6±8.6) mm. On the lateral view of CT angiography, the distance between the femoral artery and the femoral head was (20.6±4.9) mm at the level of the apex of greater trochanter. Gross observation on the cadavers found only small branches of vessels between the femoral artery and the femoral nerve. After the femoral artery and femoral nerve were respectively pulled medially and laterally, the anterior-inferior part of the femoral head was exposed directly by pulling the muscles to open the joint capsule. The exposure range of the femoral head was further expanded through internal and external rotation of the hip joint under traction. The anatomical gap between the femoral artery and the femoral nerve was named the AMA.Conclusion:AMA utilizes the potential gap between the femoral artery and the femoral nerve, providing a new surgical approach for exposure and fixation of Pipkin type Ⅰ and Ⅱ femoral head fractures.

Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) comprise a group of clonal disorders originating from hematopoietic stem cells, commonly characterized by thrombotic events, extramedullary hematopoiesis, and a propensity for malignant progression to myelofibrosis or acute leukemia. With the inclusion in the core diagnostic criteria, molecular biomarkers has exhibited applicational valus in multiple levels in the aspects of personalized therapy to subtype MPN, interpret phenotypic heterogeneity, and predict clinical outcomes. Molecular biomarkers are currently being applied in disease diagnosis, progression prediction, therapeutic strategy refinement, precision monitoring, familial MPN screening, and the development of emerging detection technologies, advancing the shift from fundamental MPN research to individualized clinical management.

Objective:To explore a new surgical approach [anteromedial approach of the hip (AMA)] for Pipkin Ⅰ and Ⅱ femoral head fractures through an imaging and anatomical study.Methods:The hip imaging data were collected of the 38 patients who had undergone lower limb CT angiography for open tibiofibular fractures at Department of Orthopaedics, The Sixth People’s Hospital, School of Medicine, Shanghai Jiao Tong University from June 2023 to January 2024. There were 20 males aged (40.9±3.5) years and 18 females aged (41.5±3.3) years. The origins and shapes of the femoral artery and its main branches were observed. The distances between the femoral head and the femoral artery, the medial femoral circumflex artery, and the lateral femoral circumflex artery were measured. Four fresh adult cadavers were collected, including 2 males and 2 females. Their ages of death were 56, 65, 72 and 78 years old, respectively. An incision was made along the axis of the limb at the midpoint of the inguinal ligament at the 4 fresh cadavers. After the femoral head was exposed through the gap between the femoral artery and the femoral nerve, the range of the femoral head exposed was marked.Results:The femoral artery ran along the anteromedial side of the femoral head. The shortest distance between the medial femoral circumflex artery and the femoral head was (13.1±5.7) mm, and the shortest distance between the origin of the lateral femoral circumflex artery and the femoral head (21.6±8.6) mm. On the lateral view of CT angiography, the distance between the femoral artery and the femoral head was (20.6±4.9) mm at the level of the apex of greater trochanter. Gross observation on the cadavers found only small branches of vessels between the femoral artery and the femoral nerve. After the femoral artery and femoral nerve were respectively pulled medially and laterally, the anterior-inferior part of the femoral head was exposed directly by pulling the muscles to open the joint capsule. The exposure range of the femoral head was further expanded through internal and external rotation of the hip joint under traction. The anatomical gap between the femoral artery and the femoral nerve was named the AMA.Conclusion:AMA utilizes the potential gap between the femoral artery and the femoral nerve, providing a new surgical approach for exposure and fixation of Pipkin type Ⅰ and Ⅱ femoral head fractures.

Objective To explore the mechanism of tumor-associated fibroblasts(CAFs)for regulating proliferation and migration of prostate cancer(PCa)cells.Methods We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa.The proliferation,migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs.We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR.In PCa cell lines C4-2 and LNCAPNC,the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation,migration,invasion,drug resistance,apoptosis and cell cycle were evaluated,and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice.Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes,whose expressions were detected in PCa cells using RT-qPCR and Western blotting.Results The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines,which exhibited significantly enhanced proliferation and migration abilities.Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells,and in C4-2 and LNCAP cells cultured alone,inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation,migration,invasion,and drug resistance.In the tumor-bearing mice,hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice.Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p,and dual luciferase reporter gene confirmed a binding site between them.In C4-2 and LNCAP cells,hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3.Conclusion CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Objective To explore the mechanism of tumor-associated fibroblasts(CAFs)for regulating proliferation and migration of prostate cancer(PCa)cells.Methods We conducted a bioinformatics analysis to identify miRNAs with high expression in PCa.The proliferation,migration and hsa-miR-18b-5p expression levels were observed in PCa cells co-cultured with CAFs.We further examined hsa-miR-18b-5p expression level in 20 pairs of PCa and adjacent tissue samples and in different PCa cell lines and normal epithelial cells using RT-qPCR.In PCa cell lines C4-2 and LNCAPNC,the effects of transfection with a hsa-miR-18b-5p inhibitor on cell proliferation,migration,invasion,drug resistance,apoptosis and cell cycle were evaluated,and the effects of has-miR-18b-5p knockdown on C4-2 cell xenograft growth and mouse survival were observed in nude mice.Dual luciferase reporter gene assay was used to validate the targeting relationship between hsa-miR-18b-5p and its target genes,whose expressions were detected in PCa cells using RT-qPCR and Western blotting.Results The expression of hsa-miR-18b-5p was significantly increased in the co-culture of CAFs and PCa cell lines,which exhibited significantly enhanced proliferation and migration abilities.Transfection with has-miR-18b-5p inhibitor strongly attenuated the effect of CAFs for promoting proliferation and migration of PCa cells,and in C4-2 and LNCAP cells cultured alone,inhibition of hsa-miR-18b-5p obviously suppressed cell proliferation,migration,invasion,and drug resistance.In the tumor-bearing mice,hsa-miR-18b-5p knockdown in the transplanted cells significantly inhibited xenograft growth and increased the survival time of the mice.Target gene prediction suggested that FBXL3 was a potential target of hsa-miR-18b-5p,and dual luciferase reporter gene confirmed a binding site between them.In C4-2 and LNCAP cells,hsa-miR-18b-5p knockdown resulted in significantly increased expression levels of FBXL3.Conclusion CAFs promotes proliferation and migration of PCa cells by up-regulating hsa-miR-18b-5p to suppress FBXL3 expression.

Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.

Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.

Objective:To construct a nomogram prediction model for survival after radical surgical resection of intrahepatic cholangiocarcinoma (ICC) based on the albumin-bilirubin index (ALBI), and to evaluate its predictive efficacy.Methods:From January 2016 to January 2020, 170 patients with ICC who underwent radical surgical resection at the People's Hospital of Zhengzhou University were retrospectively analyzed. There were 90 males and 80 females, aged (58.5±10.6) years old. Based on a ratio of 7∶3 by the random number table, the patients were divided into the training set ( n=117) and the internal validation set ( n=53). The training set was used for nomogram model construction, and the validation set was used for model validation and evaluation. Follow up was conducted through outpatient reexamination and telephone contact. The Kaplan-Meier method was used for survival analysis, and a nomogram was drawn based on variables with a P<0.05 in multivariate Cox regression analysis. The predictive strength of the predictive model was evaluated by analyzing the consistency index (C-index), calibration curve, and clinical decision curve of the training and validation sets. Results:Multivariate Cox regression analysis showed that carbohydrate antigen 19-9 (CA19-9) ≥37 U/ml ( HR=1.99, 95% CI: 1.10-3.60, P=0.024), ALBI≥-2.80 ( HR=2.43, 95% CI: 1.40-4.22, P=0.002), vascular tumor thrombus ( HR=2.34, 95% CI: 1.40-3.92, P=0.001), and the 8th edition AJCC N1 staging ( HR=2.18, 95% CI: 1.21-3.95, P=0.010) were independent risk factors affecting postoperative survival of ICC patients after curative resection. The predictive model constructed based on the above variables was then evaluated, and the C-index of the model was 0.76. Calibration curve showed the predicted survival curve of ICC patients at 3 years after surgery based on the model was well-fitted to the 45° diagonal line which represented actual survival. Clinical decision curve analysis showed that the model had a significant positive net benefit in both the training and validation sets. Conclusion:The nomograph model for survival rate after radical resection of ICC was constructed based on four variables: ALBI, CA19-9, vascular tumor thrombus, and AJCC N staging (8th edition) in this study. This model provided a reference for more accurate prognosis evaluation and treatment selection plan for ICC patients.