Objective To explore the diagnostic significance of fecal calprotectin(FC)in infectious diarrhea in children.Methods A total of 190 children with infectious diarrhea who were hospitalized in Hangzhou Children's Hospital from August 2021 to July 2024 were selected and divided into bacterial group(115 cases)and viral group(75 cases)according to type of pathogen.48 children who underwent health examination in the hospital during the same period were included in control group.The FC,white blood cell count(WBC),C-reactive protein(CRP),and procalcitonin(PCT)of three groups of children were detected.The diagnostic efficacy of FC,WBC,CRP and PCT for bacterial infectious diarrhea was evaluated by using the receiver operating characteristic(ROC)curve.Results The proportions of fever and hematochezia,the highest body temperature,frequency of defecation,and fecal white blood cells in bacterial group were significantly higher than those in viral group,while the proportion of vomiting was significantly lower than that in viral group(P＜0.05).There were statistically significant differences in levels of WBC,CRP,PCT and FC among three groups of children(P＜0.05),and the levels were all in the order of bacterial group＞viral group＞control group.The results of ROC curve showed that area under the curve(AUC)of FC for diagnosing bacterial diarrhea was 0.941,with a sensitivity of 87.0％and a specificity of 85.4％.The AUC,sensitivity and specificity of the diagnosis by FC combined with CRP were 0.987,93.0％and 97.9％respectively.Correlation analysis indicated that FC was positively correlated with WBC and CRP levels(r-0.221,0.159,P＜0.05).Conclusion FC is helpful in differentiating bacterial diarrhea from viral diarrhea,and the combined detection of FC and CRP can effectively improve the effectiveness of differential diagnosis and reduce the misdiagnosis rate.

BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were"mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents"in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.

BACKGROUND:Mesenchymal stem cell-derived exosomes inherit the advantages of low immunogenicity and strong tumor homing ability,garnering significant attention in targeted drug delivery.However,exosomes are prone to rapid clearance from the circulation before reaching target cells.Additionally,due to the complex surface properties and uptake mechanisms of exosomes,their targeting specificity is not distinctly apparent,necessitating engineered strategies to enhance delivery efficiency.OBJECTIVE:To elucidate mechanisms for enhancing the delivery efficiency of exosomes,preclinical applications,and challenges encountered by reviewing various approaches to engineering modifications of exosomes derived from mesenchymal stem cells so as to provide a theoretical basis for further clinical applications.METHODS:Relevant literature from the establishment of databases to 2024 was retrieved from databases including CNKI,VIP,WanFang,and PubMed.The search terms used were"mesenchymal stem cells,exosomes,engineered exosomes,targeted delivery,antineoplastic agents"in both English and Chinese.Literature focusing on engineered mesenchymal stem cell-derived exosomes for targeted delivery of antitumor drugs was screened,resulting in the inclusion of 85 articles for review and analysis.RESULTS AND CONCLUSION:(1)The engineering modification of mesenchymal stem cell-derived exosomes is complex and diverse.The delivery efficiency of exosomes can be improved by significantly enhancing their targeting ability to organs or tissues,increasing their residence time in the blood circulation,and reducing the expression of tumor-promoting molecules in exosomes.(2)Current examples of mesenchymal stem cell-derived exosome delivery of traditional and novel drugs demonstrate their tremendous potential.(3)There are still some safety issues that preclude their clinical translation.Future research will further improve and delve into the delivery mechanisms,with the hope of developing more efficient and safe therapeutic strategies.

Objective To explore the diagnostic significance of fecal calprotectin(FC)in infectious diarrhea in children.Methods A total of 190 children with infectious diarrhea who were hospitalized in Hangzhou Children's Hospital from August 2021 to July 2024 were selected and divided into bacterial group(115 cases)and viral group(75 cases)according to type of pathogen.48 children who underwent health examination in the hospital during the same period were included in control group.The FC,white blood cell count(WBC),C-reactive protein(CRP),and procalcitonin(PCT)of three groups of children were detected.The diagnostic efficacy of FC,WBC,CRP and PCT for bacterial infectious diarrhea was evaluated by using the receiver operating characteristic(ROC)curve.Results The proportions of fever and hematochezia,the highest body temperature,frequency of defecation,and fecal white blood cells in bacterial group were significantly higher than those in viral group,while the proportion of vomiting was significantly lower than that in viral group(P＜0.05).There were statistically significant differences in levels of WBC,CRP,PCT and FC among three groups of children(P＜0.05),and the levels were all in the order of bacterial group＞viral group＞control group.The results of ROC curve showed that area under the curve(AUC)of FC for diagnosing bacterial diarrhea was 0.941,with a sensitivity of 87.0％and a specificity of 85.4％.The AUC,sensitivity and specificity of the diagnosis by FC combined with CRP were 0.987,93.0％and 97.9％respectively.Correlation analysis indicated that FC was positively correlated with WBC and CRP levels(r-0.221,0.159,P＜0.05).Conclusion FC is helpful in differentiating bacterial diarrhea from viral diarrhea,and the combined detection of FC and CRP can effectively improve the effectiveness of differential diagnosis and reduce the misdiagnosis rate.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Humans ; Norepinephrine ; Bacterial Infections/drug therapy* ; Immunity, Innate

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective To investigate the positive detection and epidemic characteristics of enter ovirus(EV),the pathogen of hand-foot-mouth disease(HFMD),in Hangzhou,and to provide scientific basis for formulating prevention and control strategies of HFMD in the future.Methods From January 2016 to December 2022,14 259 positive cases of enterovirus universal nucleic acid detected in Hangzhou Children's Hospital were collected and analyzed retrospectively by age,gender,detection time and other factors.Results The average positive detection rate of EV was 45.48%(14 259/31 354),among which the positive detection rate of boys was 27.20%and that of girls was 18.28%,the difference was statistically significant(P<0.01).The positive detection rate of EV in children of different ages decreased with the increase of age,and the positive detection rate of EV in children under 5 years old accounted for 90.38%of all positive children.Seasonally,enteroviruses were detected throughout the year,but the incidence was high in summer,and the total positive number from May to July accounted for 49.16%of the total detected number.In terms of year,the positive detection rate of EV has shown a downward trend year by year since 2016.Conclusion There are gender differences in enterovirus infection in Hangzhou,and boys are more susceptible to enterovirus infection,especially children under 5 years old need to pay attention to EV protection.In addition,HFMD has a certain seasonality,with a high incidence in summer,and the annual detection rate has declined year by year since 2016,which may be related to the promotion of vaccines and the improvement of health awareness.

Bacterial infection is the main cause of infectious diseases in children. Antibacterials play an important role in anti infection treatment of children. At present, the treatment of antimicrobial drugs in children is facing a severe situation of bacterial resistance. In January 2020, a children′s specialized hospital carried out the practice of precise management of antibiotics in combination with key performance indicators. Through the multi sectoral linkage of management and technology, eight key performance indicators and assessment methods were set up from three levels of antibiotic use, bacterial resistance and hospital infection, to standardize the clinical application of antibiotics and continue to promote the rational use of antibiotics. This practice had improved the performance indicators of antibacterial management. Among them, the use intensity of antibacterial drugs for inpatients decreased from 40.07 DDD in 2019 to 29.00 DDD in 2021, the use rate of antibacterial drugs for inpatients decreased from 81.32% to 64.40%, the percentage of antibacterial drug expenses in total drug expenses decreased from 35.41% to 26.82%, the use proportion of non restricted antibacterial drugs in antibacterial drugs increased from 71.30% to 82.21%, and the drug resistance rate of Salmonella to β-Lactam/enzyme inhibitors decreased from 4.84% to 0.03%, and the incidence of hospital infection decreased from 1.16% to 0.96%. The precise management of antibiotics in combination with key performance indicators improved the level of rational use of antibiotics, effectively curbed bacterial resistance, achieved phased results, so as to provide a reference for the scientific management of antibiotics in children′s hospitals.

BACKGROUND: Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited. METHODS: Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis. RESULTS: EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl4 ) induced mouse liver fibrosis model. CONCLUSION EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.