1.Development and evaluation of a mortality risk prediction model for severe bacterial infections in children
Haoyu ZHA ; Rui TAN ; Haonan WANG ; Xuejian MEI ; Mingxing FAN ; Meiling PAN ; Tingting CHEN ; Jun CHEN ; Yao LIU ; Shaodong ZHAO ; Zhuo LI ; Hongjun MIAO
Chinese Journal of Emergency Medicine 2023;32(4):489-496
Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.
2.Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through A β/Kv2.1/microglial NLRP3/neuronal tau axis
Jian LU ; Qian ZHOU ; Danyang ZHU ; Xuejian ZHAO ; Yujie HUANG ; Peng CAO ; Jiaying WANG ; Xu SHEN
Chinese Journal of Pharmacology and Toxicology 2023;37(7):546-547
OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.
3.Prognosis prediction after hip fracture surgery: independent validation and recalibration of the Nottingham Hip Fracture Score
Yongjun JIN ; Peng XIAO ; Xu ZHU ; Bingtao ZHAO ; Xinfeng LIANG ; Xuejian WU
Chinese Journal of Orthopaedic Trauma 2023;25(9):777-784
Objective:To investigate the application value of the Nottingham Hip Fracture Score (NHFS) in China and establish a formula specifically designed to assess the risk for 30-day mortality after surgery for hip fracture patients in China.Methods:A retrospective study was conducted to analyze the clinical data of 824 hip fracture patients who had been treated at Department of Orthopaedics, The First Hospital Affiliated to Zhengzhou University from August 2019 to May 2022. There were 312 males and 512 females with a median age of 73 (63, 82) years. The clinical data were compared between patients with different survival outcomes. The 30-day mortality was calculated by the formula according to the patients' NHFS, and compared with the actual one to validate the effectiveness of the original prediction model. The patients were divided into a training group ( n=577) and a validation group ( n=247). Binary logistic regression analysis was performed to establish a new prediction model for the patients in the training group. The discrimination, calibration, and clinical effectiveness of the predictive model were assessed in both the training and validation groups. Results:Multivariate logistic regression analysis showed that advanced age (≥86 years old) ( OR=3.775, 95% CI: 1.099 to 12.972, P=0.035), male ( OR=3.151, 95% CI: 1.574 to 6.306, P=0.001), admission hemoglobin concentration ≤100 g/L ( OR=2.402, 95% CI: 1.189 to 4.850, P=0.015), dependence on others for care before admission ( OR=2.673, 95% CI: 1.298 to 5.505, P=0.008), and comorbidities ≥2 ( OR=4.988, 95% CI: 1.874 to 13.274, P=0.001) were identified as risk factors for postoperative 30-day mortality (all P<0.05). In validation of the original prediction model, the C-index was found to be 0.764, indicating good discrimination. However, there was a significant discrepancy between the mortality forecast by the original prediction model and the actual mortality ( P<0.05), indicating poor calibration. After the prediction model was recalibrated, 30-day mortality (%) = 100/[1 + e (5.818-NHFS×0.599)]. After the new prediction model was validated in both the training and validation groups, the C-indexes were 0.762 and 0.780, indicating a good level of discrimination. The predicted 30-day mortality by the prediction model was closely aligned with the actual mortality ( P>0.05), demonstrating good calibration. When the threshold probabilities of the training and the validation groups were 0 to 26% and 0 to 35%, respectively, the patients might benefit from clinical intervention, showing clinical effectiveness of the model. Conclusions:The NHFS can predict the risk for 30-day mortality after hip fracture surgery. The new NHFS prediction model after calibration has a good predictive value for 30-day mortality after hip fracture surgery in Chinese population.
4.Application of a 3D printed trabecular block cage in treatment of patients with basilar invagination and atlantoaxial dislocation
Min ZHANG ; Yao ZHAO ; Yuqiang WANG ; Yilin LIU ; Limin WANG ; Xuejian WU ; Hongjian LIU ; Shuhao ZHANG
Chinese Journal of Orthopaedic Trauma 2021;23(4):343-348
Objective:To explore the short-term outcomes of a 3D printed trabecular block cage to assist posterior internal fixation for the treatment of patients with basilar invagination and atlantoaxial dislocation.Methods:Between June 2017 and February 2019, 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial distraction and posterior internal fixation at Department of Orthopedics, The First Affiliated Hospital to Zhengzhou University. They were 5 males and 7 females, aged from 34 to 62 years (average, 45.6 years). 3D printed cages were inserted intraoperatively between the joints of the atlantoaxial lateral mass. The atlanto-dental interval interval (ADI), cervico-medullary angle (CMA) and distance from tip of the odontoid process to Chamberlain's line (DOCL) and the Japanese Orthopedic Association (JOA) scale were compared between preoperation and 12 months postoperation to observe the fusion of the joints of the atlantoaxial lateral mass.Results:Operation went on uneventfully in all the 12 patients. Operation time averaged 116.5 min (from 85 to 190 min), fluoroscopy frequency 9.4 times (from 6 to 21 times), and intraoperative bleeding 82.3 mL (from 50 to 210 mL). No such postoperative complications occurred as cerebrospinal leak, cerebral infarction, or breakage, displacement or loosening of implants. All patients were followed up for 18 to 42 months (mean, 26.3 months). Their preoperative JOA, ADI, CMA and DOCL [8.33±0.98, (8.66±1.64) mm, 119.63°±4.15° and (9.66±2.15) mm] were significantly improved to 14.17±1.03, (2.63±0.59) mm, 153.76°±7.88° and (2.07±0.69) mm ( P<0.05) at 12 months postoperation. Bony fusion was achieved in all the operative segments. Conclusion:In the treatment of patients with basilar invagination and atlantoaxial dislocation, a 3D-printed trabecular block cage can be used to assist posterior internal fixation to achieve satisfactory reduction and maintain the height of joint space, leading to satisfactory short-term outcomes.
5.Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates
Bing ZHAO ; Xinhui ZHANG ; Tingting YU ; Ying LIU ; Xiaoling ZHANG ; Yongfang YAO ; Xuejian FENG ; Hongmin LIU ; Dequan YU ; Liying MA ; Shangshang QIN
Acta Pharmaceutica Sinica B 2021;11(1):203-221
New Delhi metallo-β-lactamase-1 (NDM-1) is capable of hydrolyzing nearly all β-lactam antibiotics, posing an emerging threat to public health. There are currently less effective treatment options for treating NDM-1 positive “superbug”, and no promising NDM-1 inhibitors were used in clinical practice. In this study, structure–activity relationship based on thiosemicarbazone derivatives was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds 19bg and 19bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance. Further studies demonstrated compounds 19bg and 19bh were uncompetitive NDM-1 inhibitors with Ki = 0.63 and 0.44 μmol/L, respectively. Molecular docking speculated that compounds 19bg and 19bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/mL against red blood cells. In vivo experimental results showed combination of MEM and compound 19bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice. Our finding showed that compound 19bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.
6. Minor liver resection for hilar cholangiocarcinoma of Bismuth-Corlette type Ⅲ and Ⅳ
Enshan LI ; Yanlei SUN ; Xuejian LIU ; Qingpin TAI ; Rongfei ZHAO ; Shifang LYU ; Xiaoping CHEN
Chinese Journal of Surgery 2019;57(7):523-526
Objective:
To explore the clinical effect and safety of minor liver resection for hilar cholangiocarcinoma (HC) of Bismuth-Corlette type Ⅲ and Ⅳ.
Methods:
From May 2007 to May 2017, the clinical data of 108 patients with Bismuth-Corlette type Ⅲ and Ⅳ HC underwent hepatectomy were collected and analyzed retrospectively.There were 56 males and 52 females, aged (57.2±5.3) years (ranged 48-76 years) .Among the 108 cases, there were 51 cases of type Ⅲa, 40 cases of type Ⅲb and 17 cases of type Ⅳ. Small-scale hepatectomy (≤3 hepatectomy) was performed in 70 cases, including 8 cases of 4b segment resection, 28 cases of 4b segment+5 segment resection, and 34 cases of partial 4 segment+partial 7 segment+partial 1 segment resection. Large-scale hepatectomy was performed in 38 cases (>3 segments) , of which 30 cases were treated with 2 segments+3 segments+4 segments+1 segment, and 8 cases were treated with 5 segments+7 segments+8 segments+1 segment.
7.Analysis of etiology and antibiotic susceptibility in acute exacerbation of bronchiectasis
Mianmian WU ; Xuejian LIU ; Mingyu LIAO ; Li ZHAO ; Guangyu JIAO
Chinese Journal of Postgraduates of Medicine 2019;42(2):164-168
Objective To Analyze the etiology and antibiotic susceptibility in exacerbated bronchiectasis, and guide rational drug use in clinic. Methods Pathogenic microorganism culture and drug sensitivity of sputum samples of 496 cases were collected from 2015 to 2016 in Shengjing Affiliated Hospital, China Medical University. The Excel software was used to analyze the screening data and the SPSS 22.0 was used for statistical analysis to obtain the drug resistance of the bacteria to the commonly used antibiotics. Results In 469 patients, there were 551 pieces of sputum , with 198 strains positive bacterium. Positive rate was 35.93%(198/551), and bacterium was 171 strains (86.36%). Bacteria of top three positive rate was 86 strains of Pseudomonas aeruginosa (50.29%), 54 strains of Acinetobacter baumannii (31.58%) and 10 strains of Klebsiella pneumoniae (5.85%). The resistance rate of Acinetobacter baumannii and Pseudomonas aeruginosa was higher, and other pathogens also showed various degrees of tolerance to antibiotic. Conclusions The pathogens in patients with acute exacerbation of bronchiectasis are Gram-negative bacteria. Considering the characters of Pseudomonas aeruginosa, it is not suggested to use cephalosporin of the third and fourth generation in treating Pseudomonas aeruginosa. Clinical selection of antibiotics should combine with the disease characteristics of patients in our hospital.
8.Bone regeneration around dental implant with bone marrow mesenchymal stem cells sheet and platelet rich plasma
Qian LIU ; Wei ZHOU ; Huan LIU ; Zhongshan WANG ; Xuejian LI ; Yimin ZHAO
Journal of Practical Stomatology 2018;34(2):206-210
Objective: To study the bone regeneration capacity of the BMSCs cell sheets combined with PRP used with dental implant. Methods: BMSCs were isolated from young SD rats and induced to form cell sheets(BMSCs); PRP were prepared from the fresh blood of rats; PRP gel with BMSCs fragments(BMSCs + PRP) were injected into the space of dental implant of Ti and β-TCP. BMSCs, PRP and BMSCs + PRP with the implant were respectively transplanted into nude mice(n = 6). 8 weeks after transplantation bone regeneration were examined by Micro CT and hard tissue slicing. Results: The group of BMSCs + PRP showed more new bone formation around implants with blood vessel than the group of BMSCs and PRP. Conclusion: BMSCs sheets with PRP can improve the bone regeneration around dental implants.
9.Autologous bone marrow stem cells implantation to bone inducing active material combined with core decompression in the treatment of early femoral head osteonecrosis
Xiuli WANG ; Yisheng WANG ; Xuejian WU ; Xuan ZHAO ; Yi ZHANG ; Yuan MA ; Ming LI ; Zhi QIAO
Chinese Journal of Microsurgery 2017;40(2):142-145
Objective To observe the curative effect of autologous bone marrow stem cells implantation to bone inducing active material combined with core decompression in the treatment of early femoral head osteonecrosis (FHON).Methods From April,2010 to March,2012,in Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University,a total of 79 adult patients with 108 hips suffered from the early stage FHON were treated with autologous bone marrow stem cells implantation to bone inducing active material combined with core decompression through the core of the femoral canal,male of 65 cases,female of 14 cases,the mean age was 29.5 (20-50) years old.According to the etiology classification:the alcohol-induced FHON was in 54 patients with 66 hips,steroid-induced FHON in 14 patients with 20 hips,steroid and alcohol-induced ONFH was in 11patients with 22 hips.According to association research circulation osseous (ARCO)classifying,Ⅰ-A,Ⅰ-B,Ⅱ-A,Ⅱ-B phases were 6,16,8,and 78 hips,respectively.There were 43 hips in left side and 65 hips in the right side.Results All patients were followed up from 4 to 6 (4.8 ± 0.6) years.Compared with before operation,the scores of all patients were significantly increased (P < 0.05).All patients with hip pain symptoms were relieved or disappeared.The healing tine of the patients in all age groups was statistically significant (P < 0.05),and with the increase of age,the healing time was prolonged.The excellent and good rates of Ⅰ-A,Ⅰ-B,Ⅱ-Aand Ⅱ-B were 100% (6 / 6),100% (16/16),100% (8/8),and 98.7% (77/78).The X-ray showed that coarse channel osteogenic phenomenon is obvious,there is 1 case collapse of femoral head of stage Ⅱ-B,the rest were not collapse.Conclusion The treatment of early osteonecrosis of the femoral head with autologous bone marrow stem cells implantation to bone inducing active material combined with core decompressionis definitely effective,especially in patients with ARCO:Ⅰ-A,Ⅰ-B and Ⅱ-A phase,and the effect of ARCO:Ⅰ-A and Ⅱ-A is the best.
10.Changes in cerebral hemodynamics in patients with posttraumatic diffuse brain swelling after external intraventricular drainage.
Kefei CHEN ; Jirong DONG ; Tian XIA ; Chunlei ZHANG ; Wei ZHAO ; Qinyi XU ; Xuejian CAI
Chinese Journal of Traumatology 2015;18(2):90-94
PURPOSETo investigate the changes of cerebral hemodynamics pre- and post-ventricular drainage in patients with posttraumatic acute diffuse brain swelling.
METHODSTwenty-four cases of traumatic diffuse brain swelling were analyzed retrospectively. Patients in nonsurgical group were treated by medicine therapy. Patients in surgical group were treated by external ventricular drainage plus medicine therapy. The first CT perfusion scan was completed within 4-5 h after trauma and scanned again after 7 days. The changes of perfusion parameters in area-of-interest in two groups were analyzed and compared before and after treatment.
RESULTSCompared with the nonsurgical group, the value of cerebral blood volume, cerebral blood flow and mean transit time in bilateral frontal temporoparietal grey matter, basal ganglia, cerebellum, and brain stem at pre- and post-therapy were increased significantly (p < 0.05) in surgical group, and consequently the prognosis of patients undergoing surgery was also better than that of nonsurgical group.
CONCLUSIONExternal ventricular drainage can improve cerebral perfusion and increase survival quality for the patients with posttraumatic acute diffuse brain swelling.
Adult ; Aged ; Brain ; physiopathology ; Brain Edema ; physiopathology ; therapy ; Brain Injuries ; complications ; Cerebrovascular Circulation ; Drainage ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Retrospective Studies

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