1.High Expression of INF2 Predicts Poor Prognosis and Promotes Hepatocellular Carcinoma Progression
Hai-Biao WANG ; Man LIN ; Fu-Sang YE ; Jia-Xin SHI ; Hong LI ; Meng YE ; Jie WANG
Progress in Biochemistry and Biophysics 2025;52(1):194-208
ObjectiveINF2 is a member of the formins family. Abnormal expression and regulation of INF2 have been associated with the progression of various tumors, but the expression and role of INF2 in hepatocellular carcinoma (HCC) remain unclear. HCC is a highly lethal malignant tumor. Given the limitations of traditional treatments, this study explored the expression level, clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets. MethodsIn this study, we used public databases to analyze the expression of INF2 in pan-cancer and HCC, as well as the impact of INF2 expression levels on HCC prognosis. Quantitative real time polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues. The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples. Subsequently, the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments. Finally, the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments. ResultsINF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival, liver cirrhosis and pathological differentiation of HCC patients. The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC. In vivo and in vitro HCC models, upregulated expression of INF2 triggers the proliferation and migration of the HCC cell, while knockdown of INF2 could counteract this effect. INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression, thus promoting tumor progression. ConclusionINF2 is highly expressed in HCC and is associated with poor prognosis. High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression, and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
2.Study on the stability of PBMCs recovered from leukocyte-depleted filter residues
Ju LIN ; Zhiqiang XIANG ; Dongfen DU ; Fang YUAN ; Miaoyu WANG ; Yue WU ; Kaiyu HUANG ; Lieyong SANG
Chinese Journal of Blood Transfusion 2025;38(5):723-733
Objective: To identify an optimal back-flush solution for leukocyte-depleted filters that maximizes peripheral blood mononuclear cell (PBMC) recovery with high viability, long-term storage stability, and sterility of the harvested residues, thereby providing a clinically translatable strategy. Methods: Three sterile bag-packaged solutions—Saline, Solvent, and Hanks' balanced salt solution (HBSS)—were used to back-flush randomly assigned leukocyte-depleted filters. Nucleated cell recovery rate and viability of the harvested residues were compared. The optimal solution identified was applied to an expanded sample set. PBMC viability and yield were evaluated after 1h vs 48h storage of the residues. PBMCs isolated from the residues were cryopreserved in liquid nitrogen for 1 month, followed by post-thaw comparisons of viability and T-cell expansion capacity. Results: The Solvent group achieved the highest and most consistent nucleated cell recovery rate. Post-flush recovery rate from filters after 400 mL whole blood processing was (21.3±1.6)% for the Solvent group, significantly higher than Saline group (19.2±6.3)% and HBSS group (11.2±5.0)%, with residues from all groups maintaining viability >90%. No biologically significant difference in residue viability was observed between 48h vs 1h storage groups (93.3±2.3)% vs (95.7±1.8)%). PBMC recovery rates from residues showed no statistical difference between 48h vs 1h storage groups [(48.2%±9.5%)vs (40.41%±8.35%), P>0.05], with (17.7±2.6)×10
cells. After 1-month cryopreservation and 10-day expansion, PBMCs isolated from 48-hour-stored residues retained (91.2±3.2)% viability and achieved a (61.9±15.9)-fold expansion. Conclusion: The bag-packaged Solvent, as a back-flush solution, enables sterile acquisition of leukocyte-depleted filter residues through closed-system tubing connections. These residues maintained PBMC viability and recovery rates after 48h storage at 2℃-8℃, with post-cryopreservation (1-month liquid nitrogen) viability and expansion capacity remaining stable. This protocol complies with blood bank regulatory criteria, addresses the concerns about the infectious window period in cell therapy raw materials, and provides a clinically translatable strategy for PBMC-based applications.
3.Functional characterization of double-negative T cells isolated from leukoreduction filter residues.
Zhiqiang XIANG ; Yue WU ; Kaiyu HUANG ; Fuqiang WU ; Ju LIN ; Lieyong SANG ; Liming YANG
Journal of Zhejiang University. Medical sciences 2025;():1-9
OBJECTIVES:
To characterize the biological properties of double-negative T (DNT) cells isolated from leukoreduction filter residues.
METHODS:
Leukoreduction filters containing residues from 400 mL whole blood units (n=6) were collected from a blood center. Filters were back-flushed with normal saline, and the eluate was concentrated to obtain leukoreduction filter residues. Leukocytes in the residues were counted by dual-fluorescence staining. DNT cells were then isolated from the residues using antibody-mediated adsorption and density gradient centrifugation. Both cryopreserved and fresh unstimulated DNT cells derived from the residues were subjected to in vitro culture. Following culture, cells were assessed for expansion fold, viability, immunophenotype, differentiation status, and cytotoxicity against target cells using dual-fluorescence staining and flow cytometry, with comparisons made to DNT cells derived from whole blood.
RESULTS:
The leukocyte recovery rate achieved through reverse flushing of the leukocyte reduction filter was (41.9±14.7)%. Compared to whole blood, the DNT cell starting material obtained from filter residues showed no significant difference in total T-cell content (P>0.05). However, the viability and purity of the resulting DNT cell starting materials were significantly lower (both P<0.05). After 17 days of culture, DNT cells from filter residues and whole blood showed no significant differences in expansion fold, immunophenotype, differentiation status, or cytotoxicity toward target cells (all P>0.05). However, the viability of DNT cells from residues was significantly lower than that of whole blood-derived DNT cells [(86.0±4.2)% vs. (92.2±1.2)%, P<0.05]. After thawing (post 3 or 15 days of cryopreservation) and 17 days of culture, DNT cell starting materials from residues showed comparable immunophenotype, expansion fold, and differentiation status to their non-cryopreserved counterparts from the same source (all P>0.05). However, the viability of DNT cells cryopreserved for 3 days [92.4% (91.8%, 92.8%)] and the cytotoxicity against target cells of those cryopreserved for 15 days [91.3% (89.4%, 95.1%)] were significantly higher than those of non-cryopreserved DNT cells [87.8% (82.0%, 89.0%) and 70.9% (67.3%, 80.2%), respectively] (P<0.05).
CONCLUSIONS
DNT cells derived from leukoreduction filter residues exhibited highly comparable characteristics to those from whole blood in terms of expansion, purity, differentiation, and biological potency. Furthermore, their biological activity post-cryopreservation and revival remained largely similar to non-cryopreserved cells. These findings suggest that leukoreduction filter residues represent a promising alternative source of starting material for manufacturing off-the-shelf, allogeneic DNT cell therapeutics.
4.Correlation between pathological features at the positive margin and biochemical recurrence after radical prostatectomy in patients with organ-confined prostate cancer.
Xin-Huan FAN ; Yan ZHANG ; Lin-Lin ZHU ; Cheng-Yi LIU ; De-Gang CHEN ; Shi-Fang SANG ; Peng-Cheng XU
National Journal of Andrology 2025;31(3):202-207
Objective: To investigate the correlation between pathological features at the positive margins and biochemical recurrence after radical prostatectomy for prostate cancer. Methods: From June 2014 to December 2019, a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching (1∶1). One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study. All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0. BCR-free survival was estimated using the Kaplan-Meier method. An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis (CART). Cox proportional hazards regression model was used to assess the association between variables and BCR-free survival. Results: A total of 200 patients were included in this study, and 177 patients with pT2 stage were pathological after operation. The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months. A total of 28 cases of biochemical recurrence were found through PSA follow-up after surgery, including 6 cases (6.0%) in the negative margin group and 22 cases (22.0%) in the positive margin group. The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group (log rank χ2=9.336, P=0.003). It was found that the length of positive margin ≥1 mm in the positive margin group was positively correlated with postoperative biochemical recurrence. Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of positive ≥1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin. Conclusion: The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.
Humans
;
Male
;
Prostatectomy
;
Prostatic Neoplasms/pathology*
;
Neoplasm Recurrence, Local
;
Margins of Excision
;
Prostate-Specific Antigen/blood*
;
Proportional Hazards Models
;
Middle Aged
;
Aged
;
Neoplasm Staging
;
Kaplan-Meier Estimate
5.Application of drones in blood emergency support
Ju LIN ; Dongfen DU ; Lieyong SANG ; Jiafu ZHANG
Chinese Journal of Blood Transfusion 2024;37(10):1185-1188
Objective To explore the application of drones in blood emergency support during the 19th Asian Games Hangzhou in Shaoxing venue,so as to provide reference for future major events.Methods A retrospective analysis of drone delivery of emergency blood to two designated rescue hospitals in Shaoxing for the Asian Games was conducted.Ten emer-gency and 30 routine land blood delivery records from two designated hospitals in 2023 were randomly selected to compare with the blood delivery using drones.The blood temperature during the drone flight were monitored,the cold chain control during drone flight was evaluated,and the application of drone flight was reviewed.Results During the Hangzhou Asian Games,a total of 14 drones were used for blood delivery.The delivery time(min)by drone from the blood station to one of the designated hospitals was 11.83±0.09,and 20.80±3.29 by emergency land delivery and 23.23±3.54 by routine land de-livery(P<0.05),meanwhile was 17.50±0.08,24.50±3.27 and 26.57±3.23 respectively to the other hospital(P<0.05).Compared with land emergency blood delivery and routine blood delivery,blood delivery time by drone was much shorter,demonstrating better timeliness and stability.The temperature monitoring during the drone delivering showed that the suspen-ded red blood cells and platelets were in a range of 3.8-6.8℃ and 21.8-22.8℃,with a temperature difference of 0.5-0.9℃ and 0.2-1.0℃ between takeoff and landing respectively,demonstrating that the blood cold chain was under control,and the delivery ran safely and smoothly.Conclusion During major events,the use of drones for emergency blood delivery ensures the quality of the blood,with good timeliness,feasibility and operability,and is worthy of promotion and applica-tion.
6.Application of drones in blood emergency support
Ju LIN ; Dongfen DU ; Lieyong SANG ; Jiafu ZHANG
Chinese Journal of Blood Transfusion 2024;37(10):1185-1188
Objective To explore the application of drones in blood emergency support during the 19th Asian Games Hangzhou in Shaoxing venue,so as to provide reference for future major events.Methods A retrospective analysis of drone delivery of emergency blood to two designated rescue hospitals in Shaoxing for the Asian Games was conducted.Ten emer-gency and 30 routine land blood delivery records from two designated hospitals in 2023 were randomly selected to compare with the blood delivery using drones.The blood temperature during the drone flight were monitored,the cold chain control during drone flight was evaluated,and the application of drone flight was reviewed.Results During the Hangzhou Asian Games,a total of 14 drones were used for blood delivery.The delivery time(min)by drone from the blood station to one of the designated hospitals was 11.83±0.09,and 20.80±3.29 by emergency land delivery and 23.23±3.54 by routine land de-livery(P<0.05),meanwhile was 17.50±0.08,24.50±3.27 and 26.57±3.23 respectively to the other hospital(P<0.05).Compared with land emergency blood delivery and routine blood delivery,blood delivery time by drone was much shorter,demonstrating better timeliness and stability.The temperature monitoring during the drone delivering showed that the suspen-ded red blood cells and platelets were in a range of 3.8-6.8℃ and 21.8-22.8℃,with a temperature difference of 0.5-0.9℃ and 0.2-1.0℃ between takeoff and landing respectively,demonstrating that the blood cold chain was under control,and the delivery ran safely and smoothly.Conclusion During major events,the use of drones for emergency blood delivery ensures the quality of the blood,with good timeliness,feasibility and operability,and is worthy of promotion and applica-tion.
7.Exploration of the application of drones in blood emergency support
Ju LIN ; Dongfen DU ; Lieyong SANG ; Jiafu ZHANG
Chinese Journal of Blood Transfusion 2024;37(10):1185-1188
【Objective】 To explore the application of drones in blood emergency support during the 19th Asian Games Hangzhou in Shaoxing venue, so as to provide reference for future major events. 【Methods】 A retrospective analysis of drone delivery of emergency blood to two designated rescue hospitals in Shaoxing for the Asian Games was conducted. Ten emergency and 30 routine land blood delivery records from two designated hospitals in 2023 were randomly selected to compare with the blood delivery using drones. The blood temperature during the drone flight were monitored, the cold chain control during drone flight was evaluated, and the application of drone flight was reviewed. 【Results】 During the Hangzhou Asian Games, a total of 14 drones were used for blood delivery. The delivery time(min) by drone from the blood station to one of the designated hospitals was 11.83±0.09, and 20.80±3.29 by emergency land delivery and 23.23±3.54 by routine land delivery (P<0.05), meanwhile was 17.50±0.08, 24.50±3.27 and 26.57±3.23 respectively to the other hospital(P<0.05). Compared with land emergency blood delivery and routine blood delivery, blood delivery time by drone was much shorter, demonstrating better timeliness and stability. The temperature monitoring during the drone delivering showed that the suspended red blood cells and platelets were in a range of 3.8-6.8℃ and 21.8-22.8℃, with a temperature difference of 0.5-0.9 ℃ and 0.2-1.0℃ between takeoff and landing respectively, demonstrating that the blood cold chain was under control, and the delivery ran safely and smoothly. 【Conclusion】 During major events, the use of drones for emergency blood delivery ensures the quality of the blood, with good timeliness, feasibility and operability, and is worthy of promotion and application.
8.Application of drones in blood emergency support
Ju LIN ; Dongfen DU ; Lieyong SANG ; Jiafu ZHANG
Chinese Journal of Blood Transfusion 2024;37(10):1185-1188
Objective To explore the application of drones in blood emergency support during the 19th Asian Games Hangzhou in Shaoxing venue,so as to provide reference for future major events.Methods A retrospective analysis of drone delivery of emergency blood to two designated rescue hospitals in Shaoxing for the Asian Games was conducted.Ten emer-gency and 30 routine land blood delivery records from two designated hospitals in 2023 were randomly selected to compare with the blood delivery using drones.The blood temperature during the drone flight were monitored,the cold chain control during drone flight was evaluated,and the application of drone flight was reviewed.Results During the Hangzhou Asian Games,a total of 14 drones were used for blood delivery.The delivery time(min)by drone from the blood station to one of the designated hospitals was 11.83±0.09,and 20.80±3.29 by emergency land delivery and 23.23±3.54 by routine land de-livery(P<0.05),meanwhile was 17.50±0.08,24.50±3.27 and 26.57±3.23 respectively to the other hospital(P<0.05).Compared with land emergency blood delivery and routine blood delivery,blood delivery time by drone was much shorter,demonstrating better timeliness and stability.The temperature monitoring during the drone delivering showed that the suspen-ded red blood cells and platelets were in a range of 3.8-6.8℃ and 21.8-22.8℃,with a temperature difference of 0.5-0.9℃ and 0.2-1.0℃ between takeoff and landing respectively,demonstrating that the blood cold chain was under control,and the delivery ran safely and smoothly.Conclusion During major events,the use of drones for emergency blood delivery ensures the quality of the blood,with good timeliness,feasibility and operability,and is worthy of promotion and applica-tion.
9.Application of drones in blood emergency support
Ju LIN ; Dongfen DU ; Lieyong SANG ; Jiafu ZHANG
Chinese Journal of Blood Transfusion 2024;37(10):1185-1188
Objective To explore the application of drones in blood emergency support during the 19th Asian Games Hangzhou in Shaoxing venue,so as to provide reference for future major events.Methods A retrospective analysis of drone delivery of emergency blood to two designated rescue hospitals in Shaoxing for the Asian Games was conducted.Ten emer-gency and 30 routine land blood delivery records from two designated hospitals in 2023 were randomly selected to compare with the blood delivery using drones.The blood temperature during the drone flight were monitored,the cold chain control during drone flight was evaluated,and the application of drone flight was reviewed.Results During the Hangzhou Asian Games,a total of 14 drones were used for blood delivery.The delivery time(min)by drone from the blood station to one of the designated hospitals was 11.83±0.09,and 20.80±3.29 by emergency land delivery and 23.23±3.54 by routine land de-livery(P<0.05),meanwhile was 17.50±0.08,24.50±3.27 and 26.57±3.23 respectively to the other hospital(P<0.05).Compared with land emergency blood delivery and routine blood delivery,blood delivery time by drone was much shorter,demonstrating better timeliness and stability.The temperature monitoring during the drone delivering showed that the suspen-ded red blood cells and platelets were in a range of 3.8-6.8℃ and 21.8-22.8℃,with a temperature difference of 0.5-0.9℃ and 0.2-1.0℃ between takeoff and landing respectively,demonstrating that the blood cold chain was under control,and the delivery ran safely and smoothly.Conclusion During major events,the use of drones for emergency blood delivery ensures the quality of the blood,with good timeliness,feasibility and operability,and is worthy of promotion and applica-tion.
10.Imaging study on thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis
Hao-Yang ZHANG ; Ni-Sang CHEN ; Guo-Qing SHI ; Xin YE ; Shuai-Lin LI ; Xiao-Ming LI ; Bing-Hua FAN ; Ying-Sen PAN ; Xiao-Ming YING
China Journal of Orthopaedics and Traumatology 2024;37(1):26-32
Objective To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS)and the difference of physiological curvature between different types of scoliosis.Methods A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021.The patients were divided into normal group and scoliosis group.The normal group was composed of 179 patients,79 males and 100 females,aged 10 to 18 years old with an average of(12.84±2.10)years old,with cobb agle less than 10 degrees.The scol-iosis group was composed of 126 patients,33 males and 93 females,aged 10 to 18 years old with an average of(13.92±2.20)years old.The gender,age,Risser sign,thoracic kyphosis(TK)and lumbar lordosis(LL)in 2 groups were compared,and the TK and LL were also compared between different genders,different degrees of scoliosis and different segments of scoliosis.Re-sults The female ratio(P=0.001)and age(P<0.001)in scoliosis group were higher than them in normal group;the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038).TK was significantly smaller in scoliosis group than in normal group(P<0.001),but there was no significant difference in LL between the 2 groups(P=0.147).There were no significant difference in TK and LL between male and female.The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P<0.05),but there was no significant difference in LL between mild and moderate patients(P>0.05).The TK and LL in different segments scoliosis were not found significant difference.Conclusion The physiological curvature of thoracic and lumbar spine is independent of gender.The thoracic physiological curvature becomes smaller in AIS patients,but lumbar curvature remains unchanged.The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients,but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent.The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative an-terior spinal overgrowth,and the specific detailed mechanism needs to be further studied.

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