Purpose/Significance The paper discusses the application of artificial intelligence technology to the key entity recognition ofunstructured text data in the electronic medical records of lymphedema patients.Method/Process It expounds the solution of model fine-tuning training under the background of sample scarcity,a total of 594 patients admitted to the department of lymphatic surgery of Beijing Shijitan Hospital,Capital Medical University are selected as the research objects.The prediction layer of the GlobalPointer model is fine-tuned according to 15 key entity categories labeled by clinicians,nested and non-nested key entities are identified with its glob-al pointer.The accuracy of the experimental results and the feasibility of clinical application are analyzed.Result/Conclusion After fine-tuning,the average accuracy rate,recall rate and Macro_F1 ofthe model are 0.795,0.641 and 0.697,respectively,which lay a foundation for accurate mining of lymphedema EMR data.

Objective:To explore the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) from imaging perspective by analyzing voxel-based morphology (VBM) and functional connectivity (FC) in resting state functional magnetic resonance imaging (rs-fMRI).Methods:Thirty-five patients with NPSLE and 30 patients with non-NPSLE admitted to Department of Rheumatology and Immunology, Taizhou People's Hospital Affiliated to Nanjing Medical University from June 2020 to March 2023 were enrolled; 31 healthy subjects were included as healthy control group during the same period. All subjects completed routine MRI and rs-fMRI, laboratory tests (C3, C4, IgA, IgM and IgG levels), mini-mental state examination (MMSE), hospital anxiety and depression scale (HADS), and fatigue scale for motor and cognitive functions (FSMC). Whole brain gray matter volume in subjects of the 3 groups was analyzed by VBM method, and the brain regions enjoying significant differences in gray matter volume between the NPSLE group and non-NPSLE group were selected as regions of interest (ROIs) for whole brain FC analysis. Partial correlation method was used to analyze the correlations of imaging indexes in brain regions enjoying significant differences with clinical indexes and imaging scores between NPSLE group and non-NPSLE group. Efficacy of imaging indexes in brain regions enjoying significant difference in differentiating NPSLE from non-NPSLE was analyzed by receiver operating characteristic (ROC) curve.Results:(1) Covariance analysis among the 3 groups showed that the gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus was significantly different among the 3 groups ( P<0.001, FDR corrected); compared with the healthy control group, the NPSLE group had significantly reduced gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus of orbit, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus ( P<0.001, FDR corrected); compared with the non-NPSLE group, the NPSLE group had significantly decreased gray matter volume in the left inferior frontal gyrus of orbit, right rectus gyrus, and right transverse temporal gyrus ( P<0.001, FDR corrected). (2) Whole brain FC analysis with brain regions enjoying significant differences as seed points showed that Fisher z-transformed FC (zFC) in the right transverse temporal gyrus and bilateral postcentral gyrus of the NPSLE group were significantly decreased ( P<0.001, FDR corrected). (3) Partial correlation analysis showed that, in the NPSLE group, zFC from the right transverse temporal gyrus to left posterior central gyrus was negatively correlated with disease course ( r=-0.390, P=0.027); gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-cognitive ( r=-0.401, P=0.023); the gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-motor ( r=-0.374, P=0.035). (4) ROC curve found that gray matter volume in the right rectus gyrus and zFC from the right transverse temporal gyrus to the right posterior central gyrus had relatively high efficacy in differentiating NPSLE from non-NPSLE, with AUC of 0.771 (95% CI: 0.658-0.885, P<0.001) and 0.794 (95% CI: 0.685-0.904, P<0.001), respectively. Conclusion:NPSLE patients have reduced gray matter volume in multiple brain regions (concentrating in the prefrontal limbic system); and reduced FC with some brain regions is noted; multiple indexes are correlated with clinical indexes.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To retrospectively analyze the data of patients undergoing extracorporeal membrane oxygenation (ECMO) during perioperative period of cardiac transplantation and provide objective and reliable evidence for further clinical promotion.Methods:Collect the clinical data of patients undergoing heart transplantation and ECMO support in Fuwai Hospital, analyze the duration of ECMO support, combined use of aortic balloon counterpulsation (IABP), and complications during the supporting period. All statistical analyses were processed by SPSS 23.0 software. Independent sample Student's test was employed for normal distribution and Mann-Whitney U test for abormal distribution. χ2 or Fisher exact test was utilized for comparinge the classification data between groups. Results:All ECMO support models were intravenous-arterial ECMO (V-A ECMO). Eight patients successfully bridging heart transplantation through VA-ECMO. Sixty-one patients (89.7%) who had undergone cardiac transplantation were successfully weaned from ECMO while 48 patients (70.5%) survived and discharged. The most common complications during circulation support are bleeding, acute renal insufficiency, and pulmonary infection. Patients with ECMO support in the operating room had a better rate of survival and weaning off(95.6%, 84.4%) than those with ECMO at the bedside of ICU(72.2%, 27.8%).Conclusions:ECMO can provide adequate circulation and respiratory function support for heart transplant patients, and it is an indispensable treatment for patients to go through the perioperative period of heart transplant surgery smoothly. It is advocated to use IABP combined with ECMO in the early stage and at the same time to increase the perfusion of vital organs, improve the prognosis of patients and obtain good outcomes.

Objective:To systematically analyse the blood coagulation features of coronavirus disease 2019 (COVID-19) patients.Methods:An electronic search in PubMed, Scopus, Web of Science, EMbase, and CNKI to collect studies related to the blood coagulation features of COVID-19 patients from 1 January 2020 to 1 May 2020. Two reviewers independently screened literatures, extracted data and assessed the risk of bias of included studies. Then, the platelet count, D-dimer value, prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen of patients with different types of diseases were analyzed by using Stata12.0 software.Results:Thirty-nine retrospective studies involving 6 994 COVID-19 patients were included. The results of meta-analysis showed that:(1) compared with severe group, the platelet count (Weighted mean difference; WMD=20.11, 95% CI 11.53 to 28.69, P<0.001) and APTT (WMD=1.30, 95%CI 0.31 to 2.30, P=0.01) were found to be higher while D-dimer (WMD=-0.41, 95%CI-0.58 to-0.24, P<0.001), fibrinogen (WMD=-0.58, 95% CI-0.76 to-0.39, P<0.001) and PT (WMD=-0.51, 95%CI-0.92 to-0.10, P<0.001) were lower in mild group; the platelet count (WMD=-14.75, 95% CI-29.73 to-0.23, P=0.044) was found to be lower while D-dimer (WMD=1.06, 95% CI 0.65 to 1.47, P<0.001) was found to be higher in critical ill patients. (2)Compared with the survival group, the patients in death group displayed elevated levels of D-dimer (WMD=6.86, 95% CI 4.15 to 9.57, P<0.001) and PT (WMD=1.37, 95% CI 0.73 to 2.02, P<0.001) while platelet count (WMD=-36.40, 95% CI-63.23 to-9.58, P=0.008) remained low. Conclusion:Coagulation dysfunction was common in severe, critical ill and dead COVID-19 patients. Platelet count, D-dimer and PT levels were associated with the severity of the disease, and thus could be used as early warning indicators for the deterioration of the disease during hospitalization.

Objective:To investigate the correlation between glucose metabolism and neuron activity in radiation-induced brain injury of rat, and to explore the potential implication of 18F-FDG micro-PET in the assessment of radiation-induced cognitive dysfunction. Methods:Three-week-old male Sprague-Dawley (SD) rats were divided into two groups, whole-brain irradiation (WBI) group and non-irradiation control group, according to the random number table method. The WBI group was irradiated with 10 Gy X-rays using a small animal precise radiotherapy apparatus. Morris water maze (MWM) test was performed to evaluate the cognitive capability of rats. 18F-FDG micro-PET covering the whole brain was conducted and the micro-PET images were processed by SPM software. The expression of neuronal activity marker c-Fos protein in rat brain was detected by immunohistochemical staining. The neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were detected by immunofluorescence staining. Results:Three months after irradiation, MWM place navigation test showed that the latency of whole-brain irradiated rats was longer than that of the control group ( t=2.179, 3.393, 3.219, P<0.05). In MWM spatial probe test, the percentage of target quadrant exploring time was reduced in the WBI group compared with the control group ( t=3.857, P<0.01). These result suggested that WBI caused hippocampus injury-related cognitive decline. SPM analysis of micro-PET images showed that, after WBI, the glucose metabolism in the hippocampus was significantly reduced ( t=5.12, P<0.05), the neuronal active marker c-Fos protein expression was significantly downregulated ( t=14.22, P<0.01), and the neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were both decreased ( t=18.77, 9.304, P<0.01). Conclusions:Glucose metabolism in the hippocampus was reduced after WBI, in consistent with the decrease of neuron activity and the reduction of neurogenesis in this area, suggesting that 18F-FDG micro-PET could be an effective method for assessing radiation-induced cognitive dysfunction.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.

Objective To investigate the effects of diammonium glycyrrhizinate (DG) on Toll-like receptor 4 in rat alveolar epithelial cells induced by paraquat (PQ).Methods Rats in the PR and PDR groups were induced 2 h by RU486 (100 nmol/L).Then rats in the DG and PDR groups were induced 2 h by DG (0.6 mg/mL).Finally,PQ (0.6 mg/mL) were administered and induced 24h in the PQ,DG,PR and PDR groups,while,the NE group was induced 24 h by absolute ethyl alcohol (0.33 μ mol/L),and the NS group was induced 24 h without drugs.MTT assay was used to measure the cell growth and inhibitioneffects of PQ and DG on cells.The ELISA assay was applied to measure the levels of the TLR-4,Myd88,NF-κB P65 and GR.The gene expressions ofTLR-4,Myd88,NF-κB P65 and GR were detected by RT-PCR.Results The survival rate of rat alveolar epithelial cells was decreased by PQ (200,400,600,800,1 000,1 500,2 000 μmol/L),and the IC50 value for 24 h was 927.045 μmol/L.The inhibition rates were (11.74±1.44)％,(18.76±1.30)％,(28.74±0.54)％,(40.30±0.55)％,(51.24±0.76)％,(68.19±1.10)％,(83.16±0.59)％ in the 200,400,600,800,1 000,1 500,2 000 pmol/L PQ treatment groups,respectively.And the inhibition rates were (48.01±1.37)％,(40.68±2.33)％,(32.76±4.11)％,(34.12±4.3)％,(39.22±2.23)％,(51.26±-0.39)％ in the 0.2,0.4,0.6,0.8,1,and 2 mg/mL DG treatment groups,respectively.The levels of TLR4,Myd88,NF-κB P65,and TNF-a in the PQ and PR groups were higher than those in the NS group (all P＜0.01).While,the levels of GR in the PQ and PR groups were lower than that in the NS group (all P＜0.01).And,the levels of TLR4,Myd88,NF-rκB P65,and TNF-α in the DG and PDR groups were lower than those in the PQ group (all P＜0.01).But the levels of GR in the DG and PDR groups were higher than that in the PQ group (all P＜0.01).Conclusions Diammonium Glycyrrhizinate can attenuate the injury of rat alveolar epithelial cells induced by paraquat,can decrease the levels of TLR-4,Myd88,NF-KB and TNF-α,and increase the GR level.