1.Natural killer cell-derived granzyme B as a therapeutic target for alleviating graft injury during liver transplantation.
Kai WANG ; Zhoucheng WANG ; Xin SHAO ; Lijun MENG ; Chuanjun LIU ; Nasha QIU ; Wenwen GE ; Yutong CHEN ; Xiao TANG ; Xiaodong WANG ; Zhengxing LIAN ; Ruhong ZHOU ; Shusen ZHENG ; Xiaohui FAN ; Xiao XU
Acta Pharmaceutica Sinica B 2025;15(10):5277-5293
Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB+ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg -/- Rag2 -/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.
2.Total hip arthroplasty after failure of internal fixation for intertrochanteric fractures:model prediction of occult blood loss
Xiaodong LYU ; Jinrui GU ; Jingyu GAO ; Jianzhong GE
Chinese Journal of Tissue Engineering Research 2025;29(21):4506-4513
BACKGROUND:Intertrochanteric fractures of the femur are particularly common in elderly and osteoporosis patients,and treatment often requires internal fixation surgery to stabilize the fracture and promote healing. However,internal fixation surgery may occasionally fail,leading to serious problems such as nonunion of fractures,malunion,or re-fracture.OBJECTIVE:To explore the effect of artificial total hip arthroplasty on postoperative failure of internal fixation for intertrochanteric fractures of the femur and the influencing factors of postoperative occult blood loss.METHODS:Totally 86 patients with failed internal fixation of intertrochanteric fractures of the femur who were treated in First People's Hospital of Yangquan City from May 2019 to September 2022 and had complete follow-up data were collected. Using artificial total hip arthroplasty for treatment,relevant clinical indicators of the patient were recorded,and Harris score,visual analog scale score,and SF-36 score were compared and analyzed before and after surgery. Univariate and multivariate logistic regression analysis was conducted on the factors affecting occult blood loss after total hip arthroplasty. Logistic regression models and neural network models were established to predict occult blood loss. The predictive performance and accuracy of the two models were compared by drawing receiver operating characteristic curves.RESULTS AND CONCLUSION:(1) Totally 86 patients with intertrochanteric fractures of the femur were successfully treated with artificial total hip arthroplasty after internal fixation failure. (2) There were statistically significant differences in Harris score,visual analog scale score,SF-36 score,and hip active range of motion between patients before and 3,6,and 12 months after surgery (P<0.05). (3) The age,hypertension ratio,diabetes ratio,osteoporosis ratio,operation time,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease in the high occult blood loss group were significantly higher than those in the low occult blood loss group (P<0.05). The proportion of bone cement type prostheses,anterior approach,and 2-3 grade hip jointspace in the low occult blood loss group were higher than those in the high occult blood loss group (P<0.05). There was no statistically significant difference between the two groups in terms of gender ratio,body mass index,proportion of chronic bronchitis,proportion of sides,anesthesia method,and acetabular cup diameter (P>0.05). (4) Through multivariate logistic regression analysis,age,diabetes,osteoporosis,prosthesis type,surgical approach,hip joint space,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease were the risk factors for high occult blood loss after total hip arthroplasty (P<0.05). (5) After incorporating influencing factors into the logistic regression model and neural network model for predicting occult blood loss,the receiver operating characteristic curves of the two models were plotted with area under curve values of 0.882 and 0.923,sensitivity values of 0.879 and 0.886,specificity values of 0.854 and 0.908,Youden index values of 0.733 and 0.794,and accuracy values of 0.867 and 0.897,respectively. The area under curve,Youden index,and accuracy of both models were higher than those of neural network models. (6) It is concluded that total hip arthroplasty has a significant clinical effect on treating postoperative failure of internal fixation for intertrochanteric fractures of the femur,with good recovery of hip joint range of motion. Age,diabetes,osteoporosis,prosthesis type,surgical approach,hip joint space,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease are important factors for the high risk of occult blood loss after total hip arthroplasty. Logistic regression model and neural network model based on risk factors have little difference in the prediction results of occult blood loss,and neural network model is higher.
3.Development and application of chiral separation technology based on chiral metal-organic frameworks
Gege ZHU ; Li GE ; Xinyu LI ; Bing NIU ; Qin CHEN ; Dan ZHONG ; Xiaodong SUN
Journal of Pharmaceutical Analysis 2025;15(7):1409-1426
Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences.An effective way to obtain a single enantiomer is through racemates resolution.Recent literature shows that chiral metal-organic frameworks(CMOFs)have many applications in various fields because of their diverse topologies and functionalities.This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs.It highlights key advances and issues in the separation domain.In conclusion,the review provides perspectives on the challenges and prospective advance-ments of CMOFs materials and CMOFs-based separation technologies.
4.Changes in gut microbiota during diabetic nephropathy progression based on 16S rDNA sequencing technology
Qiaoying GAO ; Aimin ZHANG ; Lixiu GE ; Jie FANG ; Minghui CHEN ; Xiaodong JIA
Chongqing Medicine 2025;54(11):2515-2521
Objective To investigate changes in gut microbiota during diabetic nephropathy(DN)pro-gression using 16S rDNA sequencing technology.Methods A total of 90 male SD rats were randomly divided into a normal control group(n=10,no modeling,regular feeding)and a model group(diabetes model).The diabetes model was established by a single intraperitoneal injection of streptozotocin(STZ)at 60 mg/kg,with regular feeding.According to the feeding time after modeling,the rats were divided into 2-week,4-week,8-week,and 12-week model groups(fed for 2,4,8,and 12 weeks after model establishment),with 20 rats in each group.Blood urea nitrogen(BUN)was measured using the urease method,serum creatinine(Scr)was deter-mined by the picric acid method,and ELISA was used to detect urinary kidney injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)levels.HE,PAS,and Masson staining were used to observe renal tissue pathological changes.Gut microbiota was collected from the rats,and 16S rDNA gene sequencing was used to analyze the gut microbiota to understand changes in the gut microbiota.Results Compared with the normal control group,the levels of KIM-1 and NGAL in urine of rats in all model groups were significantly increased(P<0.05).Pathological staining results showed that,compared with the normal control group,rats in all model groups exhibited diffuse thickening of the glomerular basement membrane and pathological chan-ges such as local necrosis and vacuolar degeneration in renal tubular epithelial cells.16S rDNA sequencing re-sults indicated that the abundance and structure of intestinal microbiota in rats of all model groups changed.Compared with the normal control group,in the 8-week and 12-week model groups,the relative abundance of Bacteroides and Akkermansia decreased,while the relative abundance of Roseburia,Alloprevotella,Prevotel-laceae-Ga6A1,and Ruminococcaceae UCG-005 increased.Compared with the normal control group,in the 12-week model group,the abundance of Akkermansia decreased and that of Prevotellaceae-NK3B31 increased.Conclusion The abundance and structure of gut microbial community in DN rats under conventional feeding at different time points change significantly,further confirming the"gut-kidney axis"theory.
5.Development and application of chiral separation technology based on chiral metal-organic frameworks.
Gege ZHU ; Li GE ; Xinyu LI ; Bing NIU ; Qin CHEN ; Dan ZHONG ; Xiaodong SUN
Journal of Pharmaceutical Analysis 2025;15(7):101176-101176
Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.
6.Classification of bilobar anterolateral thigh perforator flaps based on color Doppler ultrasound and donor site evaluation
Fuqiang YANG ; Yuxiang ZHAO ; Xuejian GAO ; Jianjian GE ; Qishen FAN ; Jianguo WANG ; Xiaodong ZHAO
Chinese Journal of Orthopaedic Trauma 2025;27(6):521-528
Objective:To explore the classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography and its impact on their donor sites.Methods:A retrospective analysis was conducted of the data of 67 patients with large soft tissue defects who had been repaired with anterolateral thigh perforator flaps at Department of Orthopaedics, The Hospital Affiliated to The Second Medical University of Shandong, Department of Orthopaedics, The 80th Group Army Hospital of the People's Liberation Army, and Department of Orthopaedics, Weifang Traditional Chinese Medicine Hospital. The patients were divided into 2 groups according to their flaps used: a unilobar group and a bilobar group. In the unilobar group, 36 cases [25 males and 11 females with an age of (40.3±8.3) years] were repaired with a unilobar anterolateral thigh perforator flap from March 2015 to April 2019. In the bilobar group, 31 cases [22 males and 9 females with an age of (38.9±7.4) years] were repaired with a bilobar anterolateral thigh perforator flap from May 2019 to August 2023. Color Doppler ultrasonography was used to classify the bilobar flaps into 4 types according to the different distributions of perforating vessels: common trunk type, separate trunks type, fascia dependent type, and composite mixed type. The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were compared with the intraoperative findings in the bilobar group. One year after operation, recovery rate of donor muscle strength, rate of skin paresthesia, scar length at the donor site, the widest scar width and motor function were compared between the 2 groups.Results:The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were consistent with the intraoperative findings ( P<0.05). There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). One year after operation in the bilobar group, the recovery rate of donor muscle strength was 96.8% (30/31), significantly higher than that in the unilobar group [77.8% (28/36)], the rate of skin paresthesia 6.5% (2/31), significantly lower than that in the unilobar group [27.8% (10/36)], the scar length at the donor site (22.18±5.02) cm, significantly longer than that in unilobar group [(17.35±3.11) cm], the widest scar width (7.26±1.58) mm, significantly narrower than that in the unilobar group [(43.72±9.81) mm], and the scores of Vancouver Scar Assessment Scale and Fugl-Meyer lower limb motor function scale were (1.95±0.57) points and (8.39±2.17) points, respectively, significantly lower than those in the unilobar group [(6.38±1.72) points and (14.02±3.54) points] ( P<0.05). Conclusions:Preoperative classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography may provide guidance for flap harvesting and lobe layout of the flap. Compared to traditional unilobar flaps, bilobar ones may minimize tissue damage at a donor site.
7.Expert consensus on infection prevention and control of Creutzfeldt-Jakob disease in medical institutions
Tianxiang GE ; Yangyang JIA ; Chunhui LI ; Jianrong HUANG ; Xiujuan MENG ; Xiaodong GAO ; Jingping ZHANG ; Fu QIAO ; Lijuan XIONG ; Hui LIANG ; Wei LI ; Haiyan LOU ; Wenjuan WU ; Tianxin XIANG ; Jiansen CHEN ; Biao ZHU ; Kaijin XU ; Zhihui ZHOU ; Hongliu CAI ; Meihong YU ; Yan ZHANG ; Yanwan SHANGGUAN ; Haiting FENG ; Hangping YAO ; Lei GUO ; Tieer GAN ; Weihong ZHANG ; Jimin SUN ; Ye LU ; Qun LU ; Meng CAI ; Jin SHEN ; Yunsong YU ; Anhua WU ; Liu-yi LI ; Tingting QU
Chinese Journal of Infection Control 2025;24(4):437-450
Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.
8.Expert consensus on infection prevention and control of Creutzfeldt-Jakob disease in medical institutions
Tianxiang GE ; Yangyang JIA ; Chunhui LI ; Jianrong HUANG ; Xiujuan MENG ; Xiaodong GAO ; Jingping ZHANG ; Fu QIAO ; Lijuan XIONG ; Hui LIANG ; Wei LI ; Haiyan LOU ; Wenjuan WU ; Tianxin XIANG ; Jiansen CHEN ; Biao ZHU ; Kaijin XU ; Zhihui ZHOU ; Hongliu CAI ; Meihong YU ; Yan ZHANG ; Yanwan SHANGGUAN ; Haiting FENG ; Hangping YAO ; Lei GUO ; Tieer GAN ; Weihong ZHANG ; Jimin SUN ; Ye LU ; Qun LU ; Meng CAI ; Jin SHEN ; Yunsong YU ; Anhua WU ; Liu-yi LI ; Tingting QU
Chinese Journal of Infection Control 2025;24(4):437-450
Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.
9.Total hip arthroplasty after failure of internal fixation for intertrochanteric fractures:model prediction of occult blood loss
Xiaodong LYU ; Jinrui GU ; Jingyu GAO ; Jianzhong GE
Chinese Journal of Tissue Engineering Research 2025;29(21):4506-4513
BACKGROUND:Intertrochanteric fractures of the femur are particularly common in elderly and osteoporosis patients,and treatment often requires internal fixation surgery to stabilize the fracture and promote healing. However,internal fixation surgery may occasionally fail,leading to serious problems such as nonunion of fractures,malunion,or re-fracture.OBJECTIVE:To explore the effect of artificial total hip arthroplasty on postoperative failure of internal fixation for intertrochanteric fractures of the femur and the influencing factors of postoperative occult blood loss.METHODS:Totally 86 patients with failed internal fixation of intertrochanteric fractures of the femur who were treated in First People's Hospital of Yangquan City from May 2019 to September 2022 and had complete follow-up data were collected. Using artificial total hip arthroplasty for treatment,relevant clinical indicators of the patient were recorded,and Harris score,visual analog scale score,and SF-36 score were compared and analyzed before and after surgery. Univariate and multivariate logistic regression analysis was conducted on the factors affecting occult blood loss after total hip arthroplasty. Logistic regression models and neural network models were established to predict occult blood loss. The predictive performance and accuracy of the two models were compared by drawing receiver operating characteristic curves.RESULTS AND CONCLUSION:(1) Totally 86 patients with intertrochanteric fractures of the femur were successfully treated with artificial total hip arthroplasty after internal fixation failure. (2) There were statistically significant differences in Harris score,visual analog scale score,SF-36 score,and hip active range of motion between patients before and 3,6,and 12 months after surgery (P<0.05). (3) The age,hypertension ratio,diabetes ratio,osteoporosis ratio,operation time,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease in the high occult blood loss group were significantly higher than those in the low occult blood loss group (P<0.05). The proportion of bone cement type prostheses,anterior approach,and 2-3 grade hip jointspace in the low occult blood loss group were higher than those in the high occult blood loss group (P<0.05). There was no statistically significant difference between the two groups in terms of gender ratio,body mass index,proportion of chronic bronchitis,proportion of sides,anesthesia method,and acetabular cup diameter (P>0.05). (4) Through multivariate logistic regression analysis,age,diabetes,osteoporosis,prosthesis type,surgical approach,hip joint space,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease were the risk factors for high occult blood loss after total hip arthroplasty (P<0.05). (5) After incorporating influencing factors into the logistic regression model and neural network model for predicting occult blood loss,the receiver operating characteristic curves of the two models were plotted with area under curve values of 0.882 and 0.923,sensitivity values of 0.879 and 0.886,specificity values of 0.854 and 0.908,Youden index values of 0.733 and 0.794,and accuracy values of 0.867 and 0.897,respectively. The area under curve,Youden index,and accuracy of both models were higher than those of neural network models. (6) It is concluded that total hip arthroplasty has a significant clinical effect on treating postoperative failure of internal fixation for intertrochanteric fractures of the femur,with good recovery of hip joint range of motion. Age,diabetes,osteoporosis,prosthesis type,surgical approach,hip joint space,total blood loss,intraoperative blood loss,postoperative drainage volume,and hemoglobin decrease are important factors for the high risk of occult blood loss after total hip arthroplasty. Logistic regression model and neural network model based on risk factors have little difference in the prediction results of occult blood loss,and neural network model is higher.
10.Classification of bilobar anterolateral thigh perforator flaps based on color Doppler ultrasound and donor site evaluation
Fuqiang YANG ; Yuxiang ZHAO ; Xuejian GAO ; Jianjian GE ; Qishen FAN ; Jianguo WANG ; Xiaodong ZHAO
Chinese Journal of Orthopaedic Trauma 2025;27(6):521-528
Objective:To explore the classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography and its impact on their donor sites.Methods:A retrospective analysis was conducted of the data of 67 patients with large soft tissue defects who had been repaired with anterolateral thigh perforator flaps at Department of Orthopaedics, The Hospital Affiliated to The Second Medical University of Shandong, Department of Orthopaedics, The 80th Group Army Hospital of the People's Liberation Army, and Department of Orthopaedics, Weifang Traditional Chinese Medicine Hospital. The patients were divided into 2 groups according to their flaps used: a unilobar group and a bilobar group. In the unilobar group, 36 cases [25 males and 11 females with an age of (40.3±8.3) years] were repaired with a unilobar anterolateral thigh perforator flap from March 2015 to April 2019. In the bilobar group, 31 cases [22 males and 9 females with an age of (38.9±7.4) years] were repaired with a bilobar anterolateral thigh perforator flap from May 2019 to August 2023. Color Doppler ultrasonography was used to classify the bilobar flaps into 4 types according to the different distributions of perforating vessels: common trunk type, separate trunks type, fascia dependent type, and composite mixed type. The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were compared with the intraoperative findings in the bilobar group. One year after operation, recovery rate of donor muscle strength, rate of skin paresthesia, scar length at the donor site, the widest scar width and motor function were compared between the 2 groups.Results:The number of perforating vessels and type of perforator flap found by preoperative color Doppler ultrasound were consistent with the intraoperative findings ( P<0.05). There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). One year after operation in the bilobar group, the recovery rate of donor muscle strength was 96.8% (30/31), significantly higher than that in the unilobar group [77.8% (28/36)], the rate of skin paresthesia 6.5% (2/31), significantly lower than that in the unilobar group [27.8% (10/36)], the scar length at the donor site (22.18±5.02) cm, significantly longer than that in unilobar group [(17.35±3.11) cm], the widest scar width (7.26±1.58) mm, significantly narrower than that in the unilobar group [(43.72±9.81) mm], and the scores of Vancouver Scar Assessment Scale and Fugl-Meyer lower limb motor function scale were (1.95±0.57) points and (8.39±2.17) points, respectively, significantly lower than those in the unilobar group [(6.38±1.72) points and (14.02±3.54) points] ( P<0.05). Conclusions:Preoperative classification of bilobar anterolateral thigh perforator flaps assisted by color Doppler ultrasonography may provide guidance for flap harvesting and lobe layout of the flap. Compared to traditional unilobar flaps, bilobar ones may minimize tissue damage at a donor site.

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