1.Predictive value of FLAIR vascular hyperintensity in patients with acute ischemic stroke underwent endovascular treatment
Yaoyao YAN ; Jianxun SONG ; Guohui LIN ; Tengda HUANG ; Xinru WEN
International Journal of Cerebrovascular Diseases 2024;32(1):62-66
Endovascular treatment has become the standard treatment method for acute ischemic stroke caused by large vessel occlusion. The application of neuroimaging techniques for appropriate patient selection and prognosis prediction is of great significance for successful endovascular treatment. This article reviews the application progress of fluid-attenuated inversion recovery sequence vascular hyperintensity in patients with acute ischemic stroke underwent endovascular treatment.
2.Effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix in the treatment of children with deep burns
Yan LIANG ; Wen SHI ; Yang SHAO ; Xinzhuang LIU ; Hongmin GONG ; Guohui CAO ; Cong GAO ; Naijun XIN ; Guodong SONG
Chinese Journal of Burns 2024;40(4):348-357
Objective:To explore the effects of early debridement and conservative eschar removal followed by wound coverage with acellular dermal matrix (ADM), i.e., early surgery, in the treatment of children with deep burns.Methods:This study was a retrospective cohort study. From January 2017 to December 2022, 278 deep burned hospitalized children aged 1-7 years who met the inclusion criteria were admitted to Central Hospital Affiliated to Shandong First Medical University. According to the differences in treatment processes, 134 children who underwent early surgery+routine dressing change were enrolled in eschar removal+dressing change group (77 males and 57 females, aged 1 (1, 2) years), and 144 children who underwent only routine dressing change were enrolled in dressing change alone group (90 males and 54 females, aged 1 (1, 2) years). Fifty-one children without full-thickness burns in eschar removal+dressing change group were enrolled in eschar removal+dressing change group 1 (26 males and 25 females, aged 1 (1, 2) years), and 57 cases of the 83 children with full-thickness burns who did not undergo autologous skin grafting at the same time of early surgery (namely early skin grafting) in eschar removal+dressing change group were included in eschar removal+dressing change group 2 (37 males and 20 females, aged 1 (1, 2) years). Seventy-six children without full-thickness burns in dressing change alone group were included in dressing change alone group 1 (51 males and 25 females, aged 1 (1, 3) years), and 68 children with full-thickness burns in dressing change alone group were included in dressing change alone group 2 (39 males and 29 females, aged 1 (1, 2) years). For deep partial-thickness burn wounds and small full-thickness burn wounds in eschar removal+dressing change group, the eschar removal was performed on the basis of retaining a thin layer of denatured dermis so as to preserve the healthy tissue of the wound base, and ADM was applied to all wounds externally after eschar removal. For larger full-thickness burn wounds in this group, especially those located in the functional part of joints, eschar removal to the plane layer of viable tissue and early autologous skin grafting was needed. When the superficial wounds of children healed or tended to heal, the residual wounds were evaluated, and elective autologous skin grafting was performed if it was difficult to heal within 14 days. The healing time, intervention healing time, times of operation/dressing change, and times of intervention operation/dressing change in children with deep partial-thickness burn wounds of children in eschar removal+dressing change group, dressing change alone group, eschar removal+dressing change group 1, and dressing change alone group 1 were recorded. At the last follow-up (follow-up period was set to 7-12 months), the modified Vancouver scar scale (mVSS) scores of the most severe area of scar hyperplasia of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group and 48 children in dressing change alone group were recorded. The healing time and times of operation/dressing change of all burn wounds of children in eschar removal+dressing change group and dressing change alone group, and the healing time and times of operation/dressing change of full-thickness burn wounds of children in eschar removal+dressing change group 2 and dressing change alone group 2 were recorded. The incidences of wound infection, sepsis, fever, and fever after 5 days of burns in children of eschar removal+dressing change group and dressing change alone group during wound healing.Results:Compared with those in dressing change alone group, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group (with Z values of -11.00, -11.33, -12.64, and -11.65, respectively, P<0.05). Compared with those in dressing change alone group 1, the healing time and intervention healing time were significantly shortened, and the times of operation/dressing change and times of intervention operation/dressing change were significantly reduced in children with deep partial-thickness burn wounds in eschar removal+dressing change group 1 (with Z values of 6.57, 6.46, 8.04, and 6.57, respectively, P<0.05). At the last follow-up, the mVSS score of the most severe scar hyperplasia area of healed deep partial-thickness burn wounds of 54 children in eschar removal+dressing change group was 4.00 (3.00,5.00), which was significantly lower than 6.50 (5.00,7.00) of 48 children in dressing change alone group ( Z =-4.67, P<0.05).Compared with those in dressing change alone group, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in all burn wounds in eschar removal+dressing change group (with Z values of -5.20 and -6.34, respectively, P<0.05). Compared with those in dressing change alone group 2, the healing time was significantly shortened, and times of operation/dressing change was significantly reduced in full-thickness burn wounds in eschar removal+dressing change group 2 (with Z values of -5.22 and -5.73, respectively, P<0.05). During wound healing, the probabilities of fever and fever after 5 days of burns in children of eschar removal+dressing change group were significantly lower than those in dressing change alone group (with χ2 values of 4.13 and 3.91, respectively, P<0.05); only 1 child in dressing change alone group developed sepsis, and there was no statistically significant difference in the wound infection rate of children in the two groups ( P>0.05). Conclusions:For children with deep burns, early surgery, and early skin grafting or elective autologous skin grafting as needed, have better short-term and long-term effects than those without early surgery.
3.Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy.
Xin YUE ; Tingyu LIU ; Xuecen WANG ; Weijian WU ; Gesi WEN ; Yang YI ; Jiaxin WU ; Ziyang WANG ; Weixiang ZHAN ; Ruirui WU ; Yuan MENG ; Zhirui CAO ; Liyuan LE ; Wenyan QIU ; Xiaoyue ZHANG ; Zhenyu LI ; Yong CHEN ; Guohui WAN ; Xianzhang BU ; Zhenwei PENG ; Ran-Yi LIU
Acta Pharmaceutica Sinica B 2023;13(8):3382-3399
Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.
4.Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway
Zhiwei ZHENG ; Benyu NAN ; Chang LIU ; Dongmei TANG ; Wen LI ; Liping ZHAO ; Guohui NIE ; Yingzi HE
Journal of Pharmaceutical Analysis 2023;13(6):590-602
This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.
5.Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway.
Yingzi HE ; Zhiwei ZHENG ; Chang LIU ; Wen LI ; Liping ZHAO ; Guohui NIE ; Huawei LI
Acta Pharmaceutica Sinica B 2022;12(3):1305-1321
Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.
6.Multicenter study on the influencing factors of interdialysis blood pressure variability in maintenance hemodialysis patients
Chuling WEN ; Hongmei ZHOU ; Jie JIANG ; Zongpei JIANG ; Huijuan LI ; Guohui LIU
Chinese Journal of Nephrology 2019;35(4):247-252
Objective To assess the influencing factors of interdialysis blood pressure variability (BPV) in maintenance hemodialysis (MHD) patients from Pearl River Delta,and provide clinically useful information for the prevention and treatment of BPV.Methods MHD patients in 10 hemodialysis centers from Pearl River Delta were enrolled and analyzed retrospectively.According to the quartile of interdialysis systolic blood pressure-coefficient of variation (SBP-CV),patients were divided into four groups,and clinical data,biochemical indicators and drug use were compared among 4 groups.Binary logistic regression analysis was used to analyze the associated factors of interdialysis BPV.Results A total of 1010 MHD patients (612 males and 398 females) with the age of (56.3±13.9) years were enrolled in this study.Their dialysis duration was (48.4±36.1) months,and the median of interdialysis SBP-CV was 8.07% (5.72%,11.34%).According to the quartile of SBP-CV,the patients were divided into four groups:low BPV group (SBP-CV≤5.72%,253 cases),middle BPV group (5.72% < SBP-CV≤8.07%,252 cases),high BPV group (8.07% < SBP-CV≤11.34%,253 cases) and extremely high BPV group (SBP-CV > 11.34%,252 cases),and the dialysis duration,diabetes,ultrafiltration,interdialysis weight gain rate (IDWGR),serum calcium and the proportion of calcium channel antagonist used in the 4 groups were significantly different (all P < 0.05).Logistic multiple regression analysis showed that high IDWGR (OR=1.216,95%CI 1.108-1.435,P < 0.001) was an independent risk factors for interdialysis BPV in MHD patients,while high ultrafiltration volume (OR=0.436,95%CI 0.330-0.575,P < 0.001) and calcium channel antagonists used (OR=0.686,95%CI 0.477-0.986,P=0.042) were independent protective factors.Conclusion High IDWGR is an independent risk factor for interdialysis BPV in MHD patients,while high ultrafiltration volume and calcium channel antagonists used are protective factors for interdialysis BPV in MHD patients.
7. Clinical significance of next-generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia
Dian LOU ; Wenqing WANG ; Guohui LI ; Ren'an CHEN ; Weiwei QIN ; Ying LIU ; Yangping ZHANG ; Wen FAN ; Li LIU
Journal of Leukemia & Lymphoma 2019;28(10):577-581
Objective:
To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR).
Methods:
The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring.
Results:
There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%;
8.Observation on clinical efficacy of contact thrombolysis via radial artery or femoral artery pathway for treatment of patients with acute ischemic stroke
Tao WANG ; Renying WEN ; Guohui LI ; Chao DING ; Dong HAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2018;25(2):138-141
Objective To compare the clinical efficacy of contact thrombolytic therapy between transradial artery intervention (TRI) and transfemoral artery intervention (TFI) pathways in patients with acute ischemic stroke (AIS). Methods The clinical data of 64 patients with AIS consistent with the indication of arterial thrombolysis in the People's Hospital of Huimin County of Shandong province from January 2010 to October 2017 were treated with arterial contact thrombolysis after exclusion of contraindications, including 42 cases treated with TRI (TRI group) and 22 cases treated with TFI (TFI group), and they were analyzed retrospectively. The differences in success rate of puncture, puncture time, the interval between the sheath set to the artery and the catheter reaching the diseased vessels, the re-canalization rate of occlusive vessels, surgical time, puncture site bleeding and intracranial bleeding complications and clinical outcomes in the patients were compared between the two groups. Results The comparisons of following indicators between the TRI group and TFI group were as follows: success rate of puncture [97.6% (41/42) vs. 100.0% (22/22)], puncture time (minutes: 5.5±2.0 vs. 5.4±2.3), the interval between sheath set to the artery and catheter reaching the diseased vessel (minutes: 6.2±3.8 vs. 6.7±3.9), occlusive vascular re-canalization rate [45.2% (19/42) vs. 40.9% (9/22)], operation time (hours: 1.50±0.38 vs. 1.45±0.32), incidence intracranial bleeding complications [9.52% (4/42) vs. 9.09% (2/22)], and the differences in above indicators in comparisons between the two groups had no statistical significance (all P > 0.05); however, the complication of bleeding at puncture site in TRI group was significantly lower than that in TFI group [0 vs. 22.7% (5/22), P < 0.05]. There was no statistical difference in clinical outcomes between the two groups. Conclusion It is safe and effective to treat patients with AIS by the TRI approach.
9.Euthyphoria reduction combined with percutaneous iliosacral screw fixation for irreducible sacroiliac dislocation
Yuan XIONG ; Ming CHEN ; Qiong ZHENG ; Guohui LIU ; Minchao XU ; Wen XIONG ; Jialang HU ; Xin GUO ; Lin LU ; Wusheng KAN
Chinese Journal of Orthopaedic Trauma 2018;20(3):193-198
Objective To evaluate euthyphoria reduction combined with percutaneous iliosacral screw fixation in the treatment of irreducible sacroiliac dislocation.Methods From March 2012 to May 2015,29 patients with irreducible sacroiliac dislocation were treated using euthyphoria reduction followed by percutaneous iliosacral screw fixation.They were 18 men and 11 women,aged from 25 to 68 years (average,37.9 years).According to the Tile classification,there were 7 cases of type Cl,9 cases of type C2,and 13 cases of type C3.The intervals from injury to surgery ranged from 6 to 32 days (average,11.3 days).Results The operation time for this cohort ranged from 40 to 125 minutes (average,76.2 minutes).The intraoperative bleeding ranged from 50 to 360 mL (average,148.6 mL).Their follow-ups ranged from 24 to 41 months (average,28.9 months).According to the Matta criteria for reduction,20 cases were rated as excellent and 9 as good,yielding an excellent to good rate of 100%.Their Majeed scores at the final follow-up averaged 90.1 points (range,from 67 to 100 points),giving 20 excellent,7 good and 2 fair cases (with an excellent to good rate of 93.1%).No screw loosening or lameness of the affected limb was observed during follow-ups.Conclusions Euthyphoria reduction combined with percutaneous iliosacral screw fixation can lead to satisfactory outcomes in the treatment of irreducible sacroiliac dislocation.Additionally it may improve operative safety.
10.Effect of diabetes on clinical efficacy of hepatic arterial chemoembolization in the treatment of non-hepatitis virus hepatocellular carcinoma
Xuegang YANG ; Shi ZHOU ; Ge WU ; Zhengwen LI ; Yanyuan SUN ; Huachang WEN ; Hui WU ; Rong CAO ; Yongjun WEN ; Guohui XU
Chinese Journal of Radiology 2017;51(1):53-57
Objective To investigate the effect of diabetes on clinical efficacy of transcatheter arterial chemoembolization (TACE) in the treatment of non-viral hepatitis hepatocellular carcinoma (HCC). Methods Retrospectively analyzed the clinical data of 367 non-hepatitis virus HCC patients treated by TACE, included 153 diabetes mellitus cases (test group) and blood glucose of 214 patients was normal (control group). To assess the treatment effect after 1 month of TACE based on response evaluation criteria in solid tumors, include complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and calculate the disease control rate. Through 6 to 75 months follow-up to observed long-term efficacy, record the time to progression (TTP) and overall survival (OS) time. Survival rate were analyzed using Kaplan-Meier method and Log-rank analysis by SPSS 16.0. The single-factor analysis was used to analyze variables which variables that differed were analyzed by Cox regression. Results The disease control rate of test group was 69.9%(107/153) and control group was 74.3%(159/214), the difference was no statistically significant (P=0.125). The median time to progression (mTTP) and median overall survival (mOS) of test group were 10.0 and 15.0 months;and the mTTP and mOS of control group were 14.0 and 19.0 months, the difference were statistically significant (P=0.023 and P= 0.026). Tumor diameter ≥4.5 cm, numbers of tumor ≥3, invasion of blood vessels, α-fetoprotein≥200 μg/L, Eastern Cooperative Oncology Group score and diabetes were risk factors for OS of HCC patients. Conclusion Diabetes is unfavorable factors for overall survival of non-hepatitis HCC tread by TACE.

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