1.Clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects
Rufei DENG ; Luyao LONG ; Yanwei CHEN ; Zhenyu JIANG ; Lan JIANG ; Lijin ZOU ; Youlai ZHANG
Chinese Journal of Burns 2024;40(1):64-71
Objective:To investigate the clinical repair strategy for ischial tuberosity pressure ulcers based on the sinus tract condition and range of skin and soft tissue defects.Methods:The study was a retrospective observational study. From July 2017 to March 2023, 21 patients with stage Ⅲ or Ⅳ ischial tuberosity pressure ulcers who met the inclusion criteria were admitted to the First Affiliated Hospital of Nanchang University, including 13 males and 8 females, aged 14-84 years. There were 31 ischial tuberosity pressure ulcers, with an area of 1.5 cm×1.0 cm-8.0 cm×6.0 cm. After en bloc resection and debridement, the range of skin and soft tissue defect was 6.0 cm×3.0 cm-15.0 cm×8.0 cm. According to the depth and size of sinus tract and range of skin and soft tissue defects on the wound after debridement, the wounds were repaired according to the following three conditions. (1) When there was no sinus tract or the sinus tract was superficial, with a skin and soft tissue defect range of 6.0 cm×3.0 cm-8.5 cm×6.5 cm, the wound was repaired by direct suture, Z-plasty, transfer of buttock local flap, or V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. (2) When the sinus tract was deep and small, with a skin and soft tissue defect range of 8.5 cm×4.5 cm-11.0 cm×6.5 cm, the wound was repaired by the transfer and filling of gracilis muscle flap followed by direct suture, or Z-plasty, or combined with transfer of inferior gluteal artery perforator flap. (3) When the sinus tract was deep and large, with a skin and soft tissue defect range of 7.5 cm×5.5 cm-15.0 cm×8.0 cm, the wound was repaired by the transfer and filling of gracilis muscle flap and gluteus maximus muscle flap transfer, followed by direct suture, Z-plasty, or combined with transfer of buttock local flap; and transfer and filling of biceps femoris long head muscle flap combined with rotary transfer of the posterior femoral cutaneous nerve nutrient vessel flap; and filling of the inferior gluteal artery perforator adipofascial flap transfer combined with V-Y advancement of the posterior femoral cutaneous nerve nutrient vessel flap. A total of 7 buttock local flaps with incision area of 8.0 cm×6.0 cm-19.0 cm×16.0 cm, 21 gracilis muscle flaps with incision area of 18.0 cm×3.0 cm-24.0 cm×5.0 cm, 9 inferior gluteal artery perforator flaps or inferior gluteal artery perforator adipofascial flaps with incision area of 8.5 cm×6.0 cm-13.0 cm×7.5 cm, 10 gluteal maximus muscle flaps with incision area of 8.0 cm×5.0 cm-13.0 cm×7.0 cm, 2 biceps femoris long head muscle flaps with incision area of 17.0 cm×3.0 cm and 20.0 cm×5.0 cm, and 5 posterior femoral cutaneous nerve nutrient vessel flaps with incision area of 12.0 cm×6.5 cm-21.0 cm×10.0 cm were used. The donor area wounds were directly sutured. The survival of muscle flap, adipofascial flap, and flap, and wound healing in the donor area were observed after operation. The recovery of pressure ulcer and recurrence of patients were followed up.Results:After surgery, all the buttock local flaps, gracilis muscle flaps, gluteus maximus muscle flaps, inferior gluteal artery perforator adipofascial flaps, and biceps femoris long head muscle flaps survived well. In one case, the distal part of one posterior femoral cutaneous nerve nutrient vessel flap was partially necrotic, and the wound was healed after dressing changes. In another patient, bruises developed in the distal end of inferior gluteal artery perforator flap. It was somewhat relieved after removal of some sutures, but a small part of the necrosis was still present, and the wound was healed after bedside debridement and suture. The other posterior femoral cutaneous nerve nutrient vessel flaps and inferior gluteal artery perforator flaps survived well. In one patient, the wound at the donor site caused incision dehiscence due to postoperative bleeding in the donor area. The wound was healed after debridement+Z-plasty+dressing change. The wounds in the rest donor areas of patients were healed well. After 3 to 15 months of follow-up, all the pressure ulcers of patients were repaired well without recurrence.Conclusions:After debridement of ischial tuberosity pressure ulcer, if there is no sinus tract formation or sinus surface is superficial, direct suture, Z-plasty, buttock local flap, or V-Y advancement repair of posterior femoral cutaneous nerve nutrient vessel flap can be selected according to the range of skin and soft tissue defects. If the sinus tract of the wound is deep, the proper tissue flap can be selected to fill the sinus tract according to the size of sinus tract and range of the skin and soft tissue defects, and then the wound can be closed with individualized flap to obtain good repair effect.
2.Construction of a predictive model for postoperative subsyndromal delirium in elderly patients undergoing abdominal surgery
Shunli CHEN ; Yan LIU ; Jing CHEN ; Lingyu TANG ; Ru SONG ; Luyao CAI ; Silin ZHENG
Chinese Journal of Nursing 2024;59(16):2001-2008
Objective To analyze the influencing factors of postoperative subsyndromal delirium in elderly patients undergoing abdominal surgery,and to develop a nomogram risk prediction model.Methods A convenience sampling method was used to select 497 elderly patients who underwent abdominal surgery in a tertiary hospital in Sichuan Province from February to October 2022.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R software.The area under the subject's working characteristic curve(AUC)and Hosmer-Lemshow test were used to evaluate the discrimination and calibration of the model.Results The results of Logistic regression showed that age(OR=1.066),functional activities(OR=1.143),patient controlled intravenous analgesia(OR=5.811),transanal drainage tube(OR=2.276)and postoperative blood transfusion(OR=4.322)were independent influences on the occurrence of postoperative subsyndromal delirium.The p-values of the prediction model in both the training and validation sets were greater than 0.05;the area under the ROC curves were 0.734 and 0.691;the model was presented in the form of nomogram.Conclusion The prediction model developed in this study has good discrimination and accuracy.It can be used to assist clinical staff in identifying patients at high risk of developing postoperative subsyndromal delirium and provide the reference for developing preventive and intervention measures.
3.Application and research advances of delayed sural neurotrophic vascular flap for diabetic foot ulcers
Luyao LONG ; Yanwei CHEN ; Rufei DENG ; Zhenyu JIANG ; Youlai ZHANG
Chinese Journal of Burns 2024;40(3):296-300
Diabetic foot ulcer is one of the serious complications of diabetes. Diabetic wounds are of great difficulty to repair, causing a high amputation rate and a great burden to patients and their family members and society. Researches showed that the delayed sural neurotrophic vascular flap has a great effect in repairing diabetic foot ulcers. This article mainly reviewed the clinical status and research advances of the delayed sural neurotrophic vascular flap in repairing diabetic foot ulcers, intending to provide a reference for its application and research.
4.The efficacy and safety of protein A immunoadsorption combined with rituximab treatment for highly sensitized patients undergoing haplo-hematopoietic stem cell transplantation
Ling LI ; Wenjuan ZHU ; Qian ZHU ; Shiyuan ZHOU ; Chao MA ; Jun WANG ; Xiaohui HU ; Yue HAN ; Ying WANG ; Xiaowen TANG ; Xiao MA ; Suning CHEN ; Huiying QIU ; Luyao CHEN ; Jun HE ; Depei WU ; Xiaojin WU
Chinese Journal of Hematology 2024;45(5):468-474
Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.
5.Design of a nanozyme-based magnetic nanoplatform to enhance photodynamic therapy and immunotherapy
Bai CHEN ; Liu JIAJING ; Bai LUYAO ; Yao DAPENG ; Li XIAOFENG ; Zhang HAORAN ; Guo DONG
Journal of Pharmaceutical Analysis 2024;14(9):1320-1329
The tumor microenvironment,particularly the hypoxic property and glutathione(GSH)overexpression,substantially inhibits the efficacy of cancer therapy.In this article,we present the design of a magnetic nanoplatform(MNPT)comprised of a photosensitizer(Ce6)and an iron oxide(Fe3O4)/manganese oxide(MnO2)composite nanozyme.Reactive oxygen species(ROS),such as singlet oxygen(1O2)radicals produced by light irradiation and hydroxyl radicals(·OH)produced by catalysis,are therapeutic species.These therapeutic substances stimulate cell apoptosis by increasing oxidative stress.This apoptosis then triggers the immunological response,which combines photodynamic therapy and T-cell-mediated immunotherapy to treat cancer.Furthermore,MNPT can be utilized as a contrast agent in magnetic resonance and fluorescence dual-modality imaging to give real-time tracking and feedback on treatment.
6.The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots.
Ruibing CHEN ; Jian YU ; Luyao YU ; Liang XIAO ; Ying XIAO ; Junfeng CHEN ; Shouhong GAO ; Xianghui CHEN ; Qing LI ; Henan ZHANG ; Wansheng CHEN ; Lei ZHANG
Acta Pharmaceutica Sinica B 2024;14(1):405-420
Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.
7.Analyse the risk factors for producing anti-HLA antibodies in patients with hematological diseases
Kai JI ; Lan WANG ; Luyao CHEN ; Xiaojing BAO ; Xiaoni YUAN ; Xiaojin WU ; Jun HE
Chinese Journal of Blood Transfusion 2024;37(2):165-173
【Objective】 To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. 【Methods】 The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. 【Results】 The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count<20×109/L(P=0.020, OR1.543, 95%CI1.072-2.220), prior pregnancy(P=0.000, OR5.187, 95%CI3.689-7.293), transfusions before admission(P=0.001, OR1.762, 95%CI1.257-2.470)and total platelet transfusion volumes after admission≥30 U(P=0.000, OR2.352, 95%CI1.638-3.376). Age ≥30 years old(P=0.023, OR=1.839, 95%CI1.088-3.108)and prior pregnancy(P=0.042, OR=5.258, 95%CI1.062-26.038)are associated with the production of anti-HLA class Ⅰ and class Ⅱ antibodies, respectively. The time from disease diagnosis to antibody testing≥41 days(P=0.000, OR=2.873, 95%CI1.612-5.119), initial platelet count<20×109/L(P=0.008, OR=2.164, 95%CI1.225-3.822), prior pregnancy(P=0.002, OR=6.734, 95%CI1.993-22.751), transfusions before admission(P=0.001, OR=2.746, 95%CI1.531-4.925)and total platelet transfusion volumes after admission>30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. 【Conclusion】 Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.
8.The construction of employer's satisfaction evaluation index towards the post competency of residents
Liqiong SHEN ; Li HE ; Luyao LUO ; Jinyu CHEN ; Yanqing YE
Chinese Journal of Medical Education Research 2024;23(1):22-26
Objective:To develop employer's satisfaction evaluation index system towards post competency of residents.Methods:Using Delphi method, the employer's satisfaction evaluation index system towards post competency of residents was formulated through a two-round expert consultation among 19 experts. SPSS 20.0 was used for statistical analysis to calculate the positive coefficient, authority coefficient and coordination degree of experts.Results:For the two rounds of the expert consultation, the questionnaire recovery rate was 95.0% and 100% respectively. The experts' authority coefficient was 0.92, and the system was ultimately determined, including 5 first-level indicators, and 32 secondary indicators. The coefficient of variation (CV) of first-level indicators was 0.00, and the Kendall's W of secondary indicators was 0.663. Conclusions:Employer's satisfaction evaluation index system towards post competency of residents is scientific and reliable, which could provide employer with systematic and objective tool to evaluate residents' post competency.
9.Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous(PTEN)in sensitivity of acute myeloid leukemia to chemotherapy
LIN LIMING ; TAO JINGJING ; MENG YING ; GAN YICHAO ; HE XIN ; LI SHU ; ZHANG JIAWEI ; GAO FEIQIONG ; XIN DIJIA ; WANG LUYAO ; FAN YILI ; CHEN BOXIAO ; LU ZHIMIN ; XU YANG
Journal of Zhejiang University. Science. B 2024;25(8):700-710,中插5-中插6
Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.
10.Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe.
Hongjuan ZHANG ; Ying CHEN ; Yu ZHANG ; Luyao QIAO ; Xiangyin CHI ; Yanxing HAN ; Yuan LIN ; Shuyi SI ; Jiandong JIANG
Acta Pharmaceutica Sinica B 2023;13(5):2056-2070
Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

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