ObjectiveTo investigate whether co-activated mesenchymal stem cells（MSCs） exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups： uninfected， infected， MSC-treated， and MSC^TLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection， praziquantel was administered orally for antiparasitic treatment. At week 6， mice received either MSCs treatments （with or without pre-activation） or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen （Col-I， Col-Ⅲ） mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases（MMP） were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR， and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining， aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group， the MSC^TLR4+IFN-γ group exhibited increased body weight gain （P< 0.01）， reduced hepatic granulomatous lesion area （P< 0.001）， and decreased α-SMA， Col-I， and Col-Ⅲ mRNA levels （P< 0.01）. Additionally， the MSC^TLR4+IFN-γ group showed reduced TNF-α and IL-1β expression （P< 0.05）， as well as elevated MMP2， Mmp9， and MMP13 levels （P< 0.01）. The MSC^TLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group （P < 0.001） ， while the expression of M1 marker i-Nos decreased （P< 0.05）. Immunofluorescence confirmed a lower i-Nos+ cell ratio （P< 0.05） and higher F4/80⁺CD206⁺ cell ratio （P< 0.000 1） in the MSC^TLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSC^TLR4+IFN-γ promoted Arg-1 expression， suppressed pro-inflammatory cytokine i-Nos and TNF-α levels， consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis， potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation， providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.

Objective To construct an MRI radiomics model of cerebral damage following carbon monoxide(CO)poisoning.Methods Ninety patients with CO poisoning and 70 healthy controls(HC)were scanned by structural MRI.All patients were randomly divided into training set(n=128)and test set in a ratio of 8∶2.The radiomics features of 9 regions of interest(ROI)were automatically extracted,and each ROI was subjected to 5-fold cross-validation and 9 different types of classifiers to construct a diagnostic model.Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the diagnostic efficacy and clinical value of the model.Results The model based on the radiomics features of the whole brain gray matter(GM)and the left globus pallidus(LGP)had better diagnostic efficacy and clinical application value.The area under the curve(AUC)in the training set and the test set were 0.813,0.815 and 0.806,0.806,respectively.Conclusion The GM-based radiomics model can effectively diagnose cerebral damage following CO poisoning.

Objective To construct an MRI radiomics model of cerebral damage following carbon monoxide(CO)poisoning.Methods Ninety patients with CO poisoning and 70 healthy controls(HC)were scanned by structural MRI.All patients were randomly divided into training set(n=128)and test set in a ratio of 8∶2.The radiomics features of 9 regions of interest(ROI)were automatically extracted,and each ROI was subjected to 5-fold cross-validation and 9 different types of classifiers to construct a diagnostic model.Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the diagnostic efficacy and clinical value of the model.Results The model based on the radiomics features of the whole brain gray matter(GM)and the left globus pallidus(LGP)had better diagnostic efficacy and clinical application value.The area under the curve(AUC)in the training set and the test set were 0.813,0.815 and 0.806,0.806,respectively.Conclusion The GM-based radiomics model can effectively diagnose cerebral damage following CO poisoning.

Objective:To evaluate the role of mitochondria-associated endoplasmic reticulum membranes (MAMs) regulated by protein tyrosine phosphatase interacting protein 51 (PTPIP51) in sevoflurane-induced necroptosis in hippocampal neurons of rats using the in vitro experiment.Methods:Primary cultured hippocampal neurons from fetal rats of Sprague-Dawley rats were inoculated in culture wells (100 μl/well ) or culture flasks (3 ml/bottle) at a density of 5×10 5 cells/ml at 7 days of culture and divided into 4 groups ( n=19 each) using a random number table method: control group (C group), sevoflurane group (Sev group), sevoflurane+ siRNA-PTPIP51 transfection group (Sev+ siPTPIP51 group), and sevoflurane+ nonsense siRNA transfection group (Sev+ siNC group). The neurons were placed in a culture incubator containing 2% sevoflurane and incubated at 37 ℃ for 5 h in Sev, Sev+ siPTPIP51 and Sev+ siNC groups. Then neurons were collected for determination of the cell survival rate (by MTT method), cytoplasmic calcium concentration ([Ca 2+ ] i) and necroptosis rate (by flow cytometry), expression of PTPIP51, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) (by Western blot) and for microscopic examination of the partial length, endoplasmic reticulum circumference, and mitochondrial circumference of MAMs (with a transmission electron microscope). Results:Compared with group C, the activity of neurons was significantly decreased, the [Ca 2+ ] i and necroptosis rate were increased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was up-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were increased in group Sev ( P<0.05). Compared with group Sev, the activity of neurons was significantly increased, the [Ca 2+ ] i and necroptosis rate were decreased, the expression of PTPIP51, RIPK1, RIPK3 and p-MLKL was down-regulated, and the ratio of partial length of MAMs to endoplasmic reticulum perimeter and partial length of MAMs to mitochondrial perimeter were decreased in group Sev+ siPTPIP51 ( P<0.05), and no statistically significant changes were found in the above parameters in group Sev+ siNC ( P>0.05). Conclusions:Up-regulation of PTPIP51 expression mediates structural changes in MAMs and is involved in the process of sevoflurane-induced necroptosis in hippocampal neurons of rats.

Cytokeratin 19 (CK19) is a molecular marker of hepatic stem cells and bile duct cells. Studies have indicated that the expression of CK19 plays a key role in chemotherapeutic resistance/stem cell immunophenotype of hepatocellular carcinoma (HCC),which indicates a poor prognosis. Therefore,accurate identification of the expression of CK19 in HCC before treatment can provide important information for the choice of treatment in the future. MRI plays an important role in the diagnosis,staging and prognosis assessment of HCC. Radiomics can extract a large number of high-dimensional quantitative features from multimodal medical images,which is helpful to evaluate CK19 more objectively. This article reviews the research progress and prospect of imaging in the diagnosis of CK19-positive HCC in recent years.

Cytokeratin 19 (CK19) is a molecular marker of hepatic stem cells and bile duct cells. Studies have indicated that the expression of CK19 plays a key role in chemotherapeutic resistance/stem cell immunophenotype of hepatocellular carcinoma (HCC),which indicates a poor prognosis. Therefore,accurate identification of the expression of CK19 in HCC before treatment can provide important information for the choice of treatment in the future. MRI plays an important role in the diagnosis,staging and prognosis assessment of HCC. Radiomics can extract a large number of high-dimensional quantitative features from multimodal medical images,which is helpful to evaluate CK19 more objectively. This article reviews the research progress and prospect of imaging in the diagnosis of CK19-positive HCC in recent years.

Humans ; alpha-Synuclein/genetics* ; Parkinson Disease/pathology*

Objective:To explore the clinical efficacy and adverse reactions of albumin-bound paclitaxel (Nab-P) and conventional paclitaxel combined with cisplatin and concurrent radiotherapy for the treatment of patients with locally advanced esophageal squamous cell carcinoma.Methods:Forty-nine patients with locally advanced esophageal squamous cell carcinoma admitted to the First People's Hospital of Suqian from November 2016 to May 2020 were included. Of the 49 patients, 23 cases were treated with Nab-P combined with cisplatin and concurrent radiotherapy (NP group), 26 cases were treated with conventional paclitaxel combined with cisplatin and concurrent radiotherapy (TP group). All patients received 2 cycles of chemotherapy. The curative efficacy was evaluated one month after the end of radiotherapy, and the curative effect and adverse reactions of the two treatment regimens were compared.Results:The objective remission rate in NP group was 78.3% (18/23), and the disease control rate was 100.0% (23/23). The objective response rate in TP group was 61.5% (16/26), and the disease control rate was 92.3% (24/26). The objective response rate and disease control rate in NP group were higher than those in TP group, but the differences were not statistically significant (both P > 0.05). The common adverse reactions were mainly hair loss, loss of appetite, bone marrow suppression, radiation esophagitis, radiation pneumonia, malaise and myalgia. The incidence rate of grade 3-4 acute bone marrow suppression in NP group (8.7%, 2/23) was lower than that in TP group (38.5%, 10/26), and the difference was statistically significant ( χ2 = 4.35, P = 0.037). The incidence rate of myalgia in NP group (26.1%, 6/23) was lower than that in TP group (61.5%, 16/26), and the difference was statistically significant ( χ2 = 4.85, P = 0.028). Conclusions:Nab-P combined with cisplatin and concurrent radiotherapy has good efficacy in the treatment of patients with locally advanced esophageal squamous cell carcinoma, and the incidence rate of adverse reactions is lower than that of conventional paclitaxel combined with cisplatin and concurrent radiotherapy, so that the regimen is safe.

【Objective】 To analyze the cure time from diagnosis to cure of coronavirus disease 2019(COVID-19). 【Methods】 Based on the time of admission, diagnosis, and discharge of cured cases announced by the provincial and municipal health committees, the average period from diagnosis to discharge was calculated. And based on the aggregate data including the cumulative number of diagnoses, the number of curedcases and the number of deaths and their proportional relationship, we calculated the cure time. 【Results】 The cure time curve of 580 COVID-19 patients had skewed distribution, with a skewness of 1.09, a mean cure time of (14.6±6.7) days, a median of 13 days, and a 95% confidence interval (6.9, 21.0). The average cure time calculated based on the relationship between the cumulative number of diagnoses, the number of cured cases and the number of deaths was (13.3±3.5)d, with a median of 13.5 d. The average value of the cure time calculated based on the proportion of cured cases to the number of endpoints was (14.2±4.2)d, with the median number of 14.5 d. Based on the calculation of the relationship between the cumulative number of diagnosed cases, the number of cured cases and the number of deaths, the median cure time of cases with COVID-19 in Wuhan, Hubei Province, and the whole country was 15 days, 15.5 days and 15 days, respectively. The mediancure time for COVID-19cases in Wuhan, Hubei, and the whole country was 14 days. 【Conclusion】 The median cure time of COVID-19 is 13-15.5 days. There is some variation at different time of the outbreak, but there is not much difference between different regions.

【Objective】 To investigate the death time of patients with coronavirus disease 2019 (COVID-19). 【Methods】 The death time was calculated and analyzed using individual data and aggregated data through the daily notification of the epidemic situation and the death cases published on the website of the Heath Commission of China and provinces. 【Results】 In the 153 patients who died of COVID-19, the shortest time from onset to death was 4 days and the longest time was 50 days with the mean±standard deviation of (16.7±9.2) days. The median was 14 days and the 95% confidence interval was 4.6-42.9. The shortest time from admission to death was 1 day and the longest time was 50 days with the mean ± standard deviation of (12.1±7.8) days. The median was 11 days and the 95% confidence interval was 2-32.8. The time curve from diagnosis to death was skewed. The death time from diagnosis to death was 0 to 48 days with the mean ± standard deviation of (11.1±8.9) days. The median was 9 days, the interquartile interval was 10.5 days, and the 95% confidence interval was 0-35.4. It took 3 days from onset to admission and 1 day from admission to diagnosis. Aggregated data showed that the time from diagnosis to death of COVID-19 patients in China, China (except Hubei Province), Hubei Province and Wuhan City was 8, 9, 6 and 6 days, respectively. 【Conclusion】 The time from diagnosis to death of COVID-19 patients varied significantly, with the median time of 6-9 days in different regions.