1.Analysis of the clinical effect of tirofiban in the treatment of early neurological deterioration in patients with acute ischemic stroke
Xiaohui LI ; Xiaomin LI ; Mingyang WEI ; Huimin GUO ; Chen WANG ; Jianbin ZHANG ; Zhiqiang ZHAO
China Pharmacy 2025;36(10):1221-1225
OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology, Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method, with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment, patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally (once a day, for 14 consecutive days). The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/(kg·min) for 30 min, and then continuous intravenous infusion of 0.10 μg/(kg·min) for 47.5 h]; subsequently, patients were given Aspirin enteric-coated tablets (100 mg) and Clopidogrel bisulfate tablets (75 mg) once a day for 14 consecutive days. The clinical efficacy, the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, and hemorheological indexes before and after treatment were compared between the two groups, and the adverse reactions were recorded. RESULTS The total effective rate (87.30%) of the observation group was significantly higher than that of the control group (71.43%) (P<0.05). NIHSS scores of the two groups at 1st, 7th and 14th day after treatment, the mRS score at 90th day after treatment, and the platelet aggregation rate, whole blood viscosity, plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group, and the observation group was significantly lower than the control group at the same period (P<0.05). The total incidences of adverse reactions such as nausea, headache, fever, gastrointestinal bleeding, oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively, with no statistically significant difference (P>0.05). CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke, the addition of tirofiban can accelerate the recovery of neurological function, improve blood hyperviscosity and platelet aggregation, and improve the prognosis of patients with good safety.
2.Adrenocortical carcinoma with rhabdoid features: a case report and literature review
Mingchuan CHU ; Huimin SUN ; Hao WANG ; Jian SONG ; Yongshun GUO
Journal of Modern Urology 2025;30(1):64-68
[Objective] To investigate and summarize the clinicopathological features, diagnosis, treatment and prognosis of adrenocortical carcinoma with rhabdoid features. [Methods] The clinical diagnosis and treatment of a case of adrenocortical carcinoma with rhabdoid features admitled to Department of Urology, Weifang People's Hospital were reported.The clinical manifestations, pathological features, diagnosis and prognosis of the disease were analyzed in combination with relevant literature. [Results] A 34-year-old male patient was admitted due to scrotal distension and pain that had persisted for 6 months.Imaging examination showed a huge soft tissue tumor in the left adrenal region of the retroperitoneum with compression displacement of the left kidney, leading to obstruction of venous return in the left spermatic vein, which in turn caused varicose veins.The levels of serum renin, angiotensin, aldosterone, cortisol, and catecholamine were within normal ranges.Surgical resection of the tumor was performed, and postoperative pathological examination revealed that the tumor tissue was predominantly composed of rhabdoid cells, exhibiting positive immunohistochemical staining for INI 1, Syn, Calretinin and Vimentin.Genetic testing did not identify any deletion of SMARCB1 and SMARCA4 mutations.Therefore, the diagnosis was adrenocortical carcinoma with rhabdoid features.At the current 20-month follow-up, no recurrence or metastasis was observed.A review of the literature found that only 7 cases of this disease had been reported. [Conclusion] Adrenocortical carcinoma with rhabdoid features is a rare disease, and a definitive diagnosis is dependent upon pathological examination.Surgical resection remains the primary treatment.Long-term follow-up is essential, and further research is needed to evaluate the impact of adjuvant therapy.
3.Discussion on the accuracy of ovarian tumor diagnosis based on artificial intelligence with different scanning methods
Haizheng WANG ; Li FENG ; Sen WANG ; Huimin GUO ; Fanguo MENG
Chinese Journal of Radiological Health 2025;34(1):77-83
Objective To explore the accuracy of artificial intelligence-based diagnosis of ovarian malignant tumors and the identification of benign and malignant tumors under transabdominal scanning and transvaginal scanning methods. Methods A dataset of transabdominal and transvaginal two-dimensional ultrasound images was used and the images were preprocessed to enhance quality. The region of interest was segmented and divided into a training set and a test set. A convolutional neural network (CNN) was trained on the images in the training set, and the accuracy of the model on the test set was calculated. Results Transvaginal scanning was 14% more accurate in diagnosing malignant ovarian tumors than transabdo-minal scanning on the test set. For identifying the benign and malignant ovarian tumors containing cystic components, a mixture of transvaginal and transabdominal scanning increased the accuracy by 9.7% over transabdominal scanning alone. Conclusion CNN can identify ovarian malignant tumors under both scanning methods, but the accuracy of transvaginal scanning is higher than that of transabdominal scanning, and the CNN model has a higher accuracy in identifying benign and malignant ovarian tumors under transvaginal scanning.
4.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
5.Correlation between 1, 5-anhydroglucitol and mild cognitive impairment in elderly patients with type 2 diabetes mellitus
Lina WANG ; Xinju JIA ; Yuqing GUO ; Yan KANG ; Fan LIU ; Xiaojing LYU ; Huimin ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(7):618-623
Objective:To explore the correlation between serum 1, 5-anhydroglucitol (1, 5-AG) and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes mellitus (T2DM).Methods:A total of 160 patients with T2DM aged 60-75 years old who visited the First Hospital of Hebei Medical University from May 2021 to July 2022 were selected. According to the Montreal cognitive assessment (MoCA), all patients were divided into T2DM with MCI group (T2DM+ MCI group, n=81) and T2DM without MCI group (T2DM group, n=79). All research subjects were tested for glycated hemoglobin A1c (HbA1c), serum 1, 5-AG, serum β-amyloid peptide 42 (Aβ42), and blood biochemical indicators.SPSS 25.0 statistical software was used for data analysis. The t test, Mann-Whitney U test and χ2 test were used to compare the two groups. Binary Logistic regression analysis was used to examine the relevant influencing factors. Results:(1) Compared with T2DM group, patients in T2DM+ MCI group had significantly higher age, systolic pressure and HbA1c(all P<0.05).The level of 1, 5-AG in T2DM+ MCI group was significantly lower than that in T2DM group( (15.65±2.56 )μg/mL, (18.17±3.72 )μg/mL, P<0.01), and the level of Aβ42 was higher than that of T2DM group (2.95 (3.36) pg/mL, 1.91 (2.48) pg/mL, P<0.05). (2) Binary Logistic regression analysis results showed that HbA1c( β=0.230, OR=1.259, 95% CI=1.010-1.568, P=0.040) and Aβ42( β=0.188, OR=1.206, 95% CI=1.033-1.409, P=0.018) were the independent risk factors for MCI in elderly patients with T2DM, while 1, 5-AG ( β=-0.240, OR=0.786, 95% CI=0.698-0.886, P<0.001) was the protective factor for MCI. Conclusion:There is a positive correlation between serum 1, 5-AG and cognitive function, and the decrease of 1, 5-AG level was associated with the increased risk of MCI in elderly patients with T2DM.
6.The diagnostic value of 18F-PSMA PET/CT PRIMARY score combined with mpMRI PI-RADS sore in clinically significant prostate cancer
Hui ZHU ; Wenrui XU ; Yue GUO ; Longteng LIU ; Miao WANG ; Huimin HOU ; Chunmei LI ; Wei ZHANG ; Fugeng LIU ; Ming LIU
Chinese Journal of Urology 2024;45(6):439-444
Objective:To explore the diagnostic value of 18F-prostate specific membrane antigen (PSMA) PET/CT PRIMAY score combined with multiparameter MRI (mpMRI) PI-RADS score for clinically significant prostate cancer (CsPCa). Methods:The data of 63 patients with prostate cancer who underwent radical prostatectomy at Beijing Hospital from January 2019 to December 2023 were retrospectively analyzed. The median age was 70 (64, 75) years old with prostate-specific antigen (PSA) level of 8.46 (5.40, 14.80) ng/ml. All patients underwent 18F-PSMA PET/CT and mpMRI examination before surgery, and pathological large sections of prostate specimens were made after surgery. The prostate lesions were diagnosed and located by two radiologists and one pathologist respectively. Lesions with Gleason scores (GS)≥3+ 4 from the surgical pathology were diagnosed with CsPCa, and lesions with negative or GS=6 were diagnosed with non-CsPCa. The PSMA PET/CT images were evaluated using the PRIMARY study criteria (5-level PRlMARY score): no pattern (score of 1), diffuse transition zone or central zone(not focal) (score of 2), focal transition zone(score of 3), focal peripheral zone(score of 4), or an SUV max of at least 12 (score of 5). The degree of uptake of imaging agent in prostate lesions was semi-quantitatively evaluated using lesion-to-background ratios (LBR) of SUV max. MpMRI was evaluated according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The patients were divided into CsPCa group and non-CsPCa group based on patients and lesions. Mann-Whitney U test and chi-square test were used to compare the differences between groups. Multivariate logistic regression analysis was performed to determine the independent predictive factors of CsPCa. Receiver operator characteristic (ROC) curve was used to determine the optimal diagnostic threshold for each independent predictor. Predictive models were constructed for PRIMARY score, PI-RADS score, and their combined application, and the diagnostic performance of each model for CsPCa was compared. Results:Of all 63 patients, there were 54 cases in CsPCa group (85.7%) and 9 cases in non-CsPCa group (14.3%).There was significant difference between CsPCa group and non-CsPCa group in the serum PSA level [9.64 (6.1, 15.3) ng/ml vs. 5.6 (4.6, 7.6) ng/ml]( P<0.05). There was no statistically significant difference in age [71 (64, 75) years vs. 65 (63, 69) years], and number of lesions [2 (1, 2) vs. 2 (1, 3)] (all P>0.05). Of all 109 lesions, there were 81 lesions in CsPCa group(including 49 lesions with Gleason score = 3+ 4, 16 lesions with Gleason score=4+ 3, 14 lesions with Gleason score = 8, and 2 lesions with Gleason score>8) and 28 lesions in non-CsPCa group(including 14 lesions with Gleason score = 3+ 3 and 14 with benign prostate lesions). There was significant difference between CsPCa group and non-CsPCa group in PRIMARY score [4 (3, 5) vs. 2 (1, 4)], LBR [2.69 (2.08, 4.48) vs. 1.89 (1.45, 2.48)], PI-RADS score [4 (3, 5) vs. 2 (2, 3)] (all P<0.05). There was no statistically significant difference in the lesion distribution including the number of lesions located in the transition zone [15(18.5%) vs. 8(28.6%)] and in the peripheral zone[66(81.5%) vs. 20(71.4%)]( P>0.05). Multivariate logistic regression analysis indicated that PRIMARY score ( OR=2.134, 95% CI 1.429-3.187) and PI-RADS score ( OR=2.689, 95% CI 1.618-4.469) were independent predictors of CsPCa (both P<0.01). ROC curves analysis revealed that the cut-off value for diagnosing CsPCa was both 3 for PRIMARY score and PI-RADS score. The accuracy for PRIMARY score, PI-RADS score, and their combined complication in diagnosing CsPCa was 72%, 67%, and 83%, respectively. The sensitivity was 72%, 63%, and 91%, and the specificity was 75%, 79%, and 57%, respectively. The positive predictive value was 89%, 89%, and 86%, and the negative predictive value was 48%, 42%, and 70%, respectively. The area under the curve of the PRIMARY score, PI-RADS score, and their combined complication of the ROC curve for CsPCa were 0.733 (95% CI 0.624-0.842), 0.708 (95% CI 0.599-0.817), and 0.743 (95% CI 0.623-0.862), respectively. The diagnostic efficacy of their combined complication was higher than PRIMARY score or PI-RADS score alone (both P<0.01). Conclusions:Both the 18F-PSMA PET/CT PRIMAY score and the mpMRI PI-RADS score have good diagnostic value for CsPCa. The combined application of the two imaging parameters can improve the accuracy, sensitivity, and negative predictive value, which have a higher diagnostic efficiency of CsPCa.
7.Role of GABAergic neuron in bed nucleus of stria terminalis in isoflurane-induced general anesthesia-emergence in mice
Xiaoyu GUO ; Huimin WU ; Dan WANG ; Hailong DONG
Chinese Journal of Anesthesiology 2024;44(5):587-592
Objective:To investigate the role of GABAergic neurons in the bed nucleus of the stria terminalis (BNST) in isoflurane-induced general anesthesia-emergence in mice.Methods:Twenty-three healthy male Vgat-Cre transgenic mice, aged 8-10 weeks, weighing 22 g, were used in the study. In the immunofluorescence staining experiment, 8 mice were selected and divided into 2 groups ( n=4 each) using a random number table method: oxygen group and isoflurane group. Oxygen group inhaled oxygen at a rate of 1.0 L/min for 2 h, while isoflurane group inhaled 1.4% isoflurane + 1.0 L/min oxygen for 2 h. The animals were then sacrificed, and brain tissues were removed and subjected to immunofluorescence staining for determination of the expression of c-Fos and the rate of co-labeling with GABA neurons. For the optogenetic experiment, 15 mice were divided into 3 groups ( n=5 each) using a random number table method: control group (CON group), optogenetic excitation group (CHR2 group) and optogenetic inhibition group (eNpHR group). The rAAV-Ef1a-DIO-mCherry, rAAV-Ef1a-DIO-CHR2-mCherry, and rAAV-Ef1a-DIO-eNpHR3.0-mCherry viruses were injected to the BNST brain region. After 3 weeks of virus expression, the mice were exposed to 1.0% isoflurane + 1.0 L/min oxygen, and their cortical EEG was simultaneously monitored. When the mice reached a stable anesthetic state, optogenetic methods were utilized to modulate the viability of GABAergic neurons in the BNST brain region, and the burst suppression ratio (BSR) of the cortical EEG was recorded at 2 min before light stimulation and 2 min of light stimulation. Results:Compared with oxygen group, the rate of c-Fos co-labeling with GABA neurons in the BNST brain region was significantly reduced ( P<0.05), and the c-Fos-positive neurons were reduced in isoflurane group. Compared with CON group or with the prestimulation level, BSR was significantly decreased in CHR2 group ( P<0.001), and no significant change was found in BSR during light stimulation in eNpHR group ( P>0.05). Conclusions:Decreased viability of GABAergic neurons in the BNST brain region may be involved in the process of loss of consciousness in isoflurane-anesthetized mice, while increased viability of GABAergic neurons in the BNST brain region promotes the transition from anesthesia to emergence.
8.Application of single metal clip traction to endoscopic submucosal dissection for duodenal lesions
Dandan ZHU ; Xiaotan DOU ; Huimin GUO ; Min CHEN ; Lei WANG ; Chenggong YU
Chinese Journal of Digestive Endoscopy 2024;41(9):707-711
Objective:To assess the safety and efficacy of single metal clip traction-assisted endoscopic submucosal dissection (ESD) for the treatment of duodenal lesions.Methods:Data of 45 patients with duodenal lesions who underwent ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between April 2021 and October 2022 were retrospectively recruited. Among them, 19 patients received single metal clip traction- assisted ESD while 26 patients received traditional ESD. The incidence of complications, dissection speed, en bloc resection rate and R0 resection rate of the two groups were mainly observed. Secondary observation indexes included specimen longer diameter, shorter diameter and area.Results:All 45 procedures were successfully completed, with the procedure time of 44.0 (27.0, 67.0) min for the single metal clip traction- assisted ESD group and 34.0 (24.0, 43.5) min for the traditional ESD group ( Z=-1.678, P=0.093). In the single metal clip traction-assisted ESD group, 2 cases (10.5%) had complications, including 1 intraoperative perforation and 1 postoperative bleeding (approximately 20 mL). There were three cases (11.5%) of complications in the traditional ESD group, including 1 case of postoperative bleeding (approximately 50 mL) and 2 cases of postoperative perforation, with no significant intergroup variation ( P=1.000). The dissection speed of the single metal clip traction-assisted ESD group was 16.0 (11.0, 25.8) mm 2/min, significantly larger than that of the traditional ESD group [5.3 (2.2, 21.1) mm 2/min, Z=-2.287, P=0.022]. The en block resection rate and R0 resection rate of the single metal clip traction-assisted ESD group were both 100.0% (19/19). Additionally, the specimen longer diameter, shorter diameter and area of the single metal clip traction-assisted ESD group were 34.0 (22.0, 45.0) mm, 25.0 (20.0, 34.0) mm, and 745.8 (380.0, 1 342.4) mm 2, respectively, significantly larger than those of the traditional ESD group of 20.0 (12.8, 30.3) mm ( Z=-3.119, P=0.002), 14.0 (8.8, 21.3) mm ( Z=-3.417, P=0.001), 190.4 (84.0, 498.7) mm 2 ( Z=-3.275, P=0.001). Conclusion:Single metal clip traction is safe and effective for duodenal ESD, demonstrating a notable improvement in the dissection speed, especially suitable for large duodenal lesions.
9.Investigation of the cognition of consequences of scientific misconduct of trainees in physician standardized training in Guangxi
Yizhao LI ; Lulin CHEN ; Xiaoli TAN ; Yue LI ; Huimin HUANG ; Jie WANG ; Xiaoyan GUO
Chinese Journal of Medical Science Research Management 2024;37(3):224-229
Objective:This study aimed to assess the awareness of trainees in physician standardized training towards the consequences of scientific misconduct and identify the main influencing factors, additionally, to provide targeted suggestions.Methods:A questionnaire survey was conducted among 6 200 trainees from 17 National standardized training bases for residencies in Guangxi. The cognitive status of the consequences of scientific misconduct were analyzed and factors affecting trainees' cognition were examined in terms of grade, education level, research experience, publication experience, research integrity training experience, and research integrity knowledge level.Results:The findings indicated that the awareness of trainees towards the consequences of scientific misconduct requires improvement. Notably, trainees from the 2020 and 2021 grade cohorts, with a master′s degree or above, having led research projects, having participated in research integrity training, and with a high level of research integrity knowledge scored higher on the cognitive assessment of the impact of research misconduct.Conclusions:Training bases should prioritize the education of research integrity among trainees, enhance their identification with scientific research integrity, raise their awareness of the seriousness of the consequences of scientific misconduct, and uphold the belief of adhering to the bottom line of academic ethics.
10.Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.
Jiawen ZHOU ; Xinyue SUN ; Xuelian CHEN ; Huimin LIU ; Xiulian MIAO ; Yan GUO ; Zhiwen FAN ; Jie LI ; Yong XU ; Zilong LI
Acta Pharmaceutica Sinica B 2024;14(1):256-272
Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

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