OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

Objective:To analyze the risk factors for in-hospital malignant ventricular arrhythmia (MVA) in acute myocardial infarction (AMI) and to construct and validate a risk prediction model.Methods:This study was a retrospective cohort study. Patients aged≥18 years who were admitted to Qilu Hospital of Shandong University with a diagnosis of AMI and underwent coronary angiography (CAG) from May 2016 to March 2023 were selected, and the patients' clinical routine test indicators and CAG results were collected. Univariate and bidirectional stepwise logistic regression were used to screen out the risk factors for constructing the best prediction model. The prediction model was constructed by combining the results of multivariate logistic regression. The Hosmer-Lemeshow test and ROC curve, calibration curve, and decision curve were drawn to evaluate the model. The nomogram was drawn to visualize the model, and the Bootstrap self-sampling method was used for internal validation. The ROC curve was drawn to evaluate the predictive performance of each risk factor and prediction model. Finally, a multicollinearity test was performed.Results:Among the 4 205 patients finally included in the study, 115 patients (2.735%) developed MVA during hospitalization. The predictive factors screened out included age (X1), diastolic blood pressure (X2), respiratory rate (X3), blood glucose (X4), serum potassium (X5), logarithmic NT-proBNP (X6), myocardial infarction type (NSTEMI=X7, unclassified=X8), J wave (X9), Killip grade (Ⅱ=X10, Ⅲ=X11, Ⅳ=X12), and the regression equation was ln(p/1-p)=-4.699+0.029×X1-0.012×X2+0.059×X3+0.148×X4-1.175×X5+0.866×X6-1.427×X7-0.475×X8+0.758×X9+0.294×X10+0.902×X11+1.815×X12. The area under the ROC curve (AUC) of the model was 0.855 (95% CI: 0.816-0.894), and the Hosmer-Lemeshow test ( χ2=14.178, P=0.077) and the calibration curve showed that the predicted probability was consistent with the actual probability. The probability threshold of 0% to 65% had a better clinical net benefit. The area under the internal validation ROC curve (AUC) was 0.855, 95% CI: 0.813-0.891. The prediction performance of the nine variables was stronger than that of any single variable. There was no multicollinearity between the variables. Conclusions:Age, diastolic blood pressure, respiratory rate, blood glucose, serum potassium, NT-proBNP, type of AMI, J wave, and Killip class are forecasting indicator for in-hospital MVA in AMI. The risk prediction model based on the above factors has good predictive performance.

Objective:To investigate the efficacy of neutrophil elastase inhibitor in children with acute respiratory distress syndrome（ARDS）.Methods:A total of 168 children with moderate to severe ARDS who were hospitalized in the Department of Pediatric Intensive Care Unit，the Affiliated Children′s Hospital of Xi′an Jiaotong University and Children's Emergency Center of Gansu Provincial Central Hospital from January 2022 to December 2023 were selected. Eighty-seven children receiving neutrophil elastase inhibitors were treated as the treatment group and 81 children receiving conventional treatment as the control group. The dynamic changes of general data，clinical indicators and ventilator parameters at 24 h，48 h and 72 h were compared between the two groups. Mortality at 28 days was the primary endpoint. Kaplan-Meier curve and Log-Rank test were used to evaluate cumulative survival.Results:There was no significant difference in general information and clinical characteristics between the two groups.Compared with the control group，arterial partial pressure of oxygen（PaO 2）/fraction of inspired oxygen（FiO 2）in the treatment group increased significantly at 48 h［（160.28±5.90）mmHg（1 mmHg=0.133 kPa）vs（141.04±4.01）mmHg， P<0.05］and 72 h［（227.58±6.85）mmHg vs（180.86±4.08）mmHg， P<0.05］，and the differences were statistically significant.The platform pressure in the treatment group were lower than that of the control group at 24 h［（28.18±3.95）cmH 2O（1cmH 2O=0.098 kPa）vs（30.15±7.75）cmH 2O， P<0.05］，48 h［（25.56±4.06）cmH 2O vs（29.07±5.01）cmH 2O， P<0.05］，72 h［（24.95±2.82）cmH 2O vs（27.12±6.51）cmH 2O， P<0.05］，and the differences were statistically significant. IL-8 in the treatment group were lower than that of the control group at 48 h［（78.26±14.05）ng/L vs（86.02±15.01）ng/L， P<0.05］and 72 h［（58.38±15.56）ng/L vs（68.68±18.05）ng/L， P<0.05］，and the differences were statistically significant.The survival curve showed that the cumulative survival rate of the treatment group was higher than that of the control group，the difference between the two groups was statistically significant（ χ2=4.549， P=0.033）. Conclusion:Neutrophil elastase inhibitors can reduce the lung injury of ARDS patients by inhibiting the inflammatory response induced by neutrophils，and ultimately improve the prognosis of the disease.

Objective:To evaluate the safety and efficacy of immunoadsorption with protein A column(PA-IA) in refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children.Methods:The clinical data of 8 children with anti-NMDAR encephalitis who failed to receive first-line treatment from January 2022 to June 2023 in PICU of Xi'an Children's Hospital were retrospectively collected.Clinical features,modified Rankin score (mRS),anti-NMDAR antibody titers in serum and cerebrospinal fluid(CSF),cells count in CSF,protein level in CSF,serum IgG,complement C3,C4 level were analyzed before and after immunoadsorption therapy. All adverse events that occurred during treatment were recorded in detail.Result:Among the 8 children,there were 5 males and 3 females,aged 5 to 12 years old,and each patient was immunized 6 to 10 times,and 75 times of PA-IA treatment were performed. The mRS score decreased in 8 children after PA-IA treatment. Blood IgG level,CSF cell number,protein level in CSF,blood complement C3 and C4 levels,and antibody titers related in blood and CSF were all lower than those before PA-IA treatment. The differences were all statistically significant ( P<0.001).During 75 times of treatment,only 1 case of membrane rupture occurred during treatment,the treatment was stopped and continued after the plasma separator was replaced,with no other adverse reactions. Conclusion:PA-IA could effectively improve the clinical symptoms and neurological function of children with refractory anti-NMDAR encephalitis with good safety,but its exact efficacy in children with anti-NMDAR encephalitis needs to be verified by prospective studies with larger samples.

Objective:To investigate the efficacy of nafamostat mesylate in traumatic extracorporeal membrane oxygenation (ECMO) therapy.Methods:Patients admitted to the intensive care units of Children's Hospital Affiliated to Xi'an Jiaotong University and Gansu Provincial Maternal and Child Health Hospital for ECMO-assisted cardiopulmonary support due to trauma from January 2021 to December 2024 were selected as the study subjects. Based on different anticoagulation strategies, patients were divided into the nafamostat mesylate group( n=11) and the common heparin group( n=10). The general conditions of the two groups were compared. In addition, differences in various clinical indicators during the ECMO-assisted process were compared, including white blood cell count (WBC), platelet count (PLT), hemoglobin level (Hb), hematocrit (HCT), prothrombin time(PT), activated partial thromboplastin time (APTT), thrombin time(TT), fibrinogen(FIB) and D-dimer. Furthermore，the differences in the total volume of component blood transfusions, coagulation substances, complications and prognosis between the two groups were compared. Results:No statistically significant differences were observed between the two groups regarding age, gender, weight, type of ECMO support, type of trauma, presence of active bleeding, or rate of surgical intervention. There were no statistically significant differences in WBC, PLT, Hb, HCT, PT, APTT, TT, FIB, and D-dimer between the two groups of patients prior to the initiation of ECMO support (all P>0.05). Compared with the common heparin group, children in the nafamostat mesylate group had lower PT[(21±6)s vs. (27±3)s; (20±4) vs. (28±5)], APTT[(68±8)s vs. (89±12)s; (64±15)s vs. (85±21)s], TT [(25±11)s vs. (31±13)s; (24±8)s vs. (35±6)s], and D-dimer[(5.8±1.1) μg/mL vs. (11.5±5.6) μg/mL; (4.2±1.8) μg/mL vs. (14.6±2.5) μg/mL],and higher FIB[(2.1±0.5) g/L vs. (1.6 ± 0.3) g/L; (2.4 ± 0.4) g/L vs. (1.3 ± 0.6) g/L] when ECMO assisted for 24 h and 72 h,the differences were all statistically significant(all P<0.05). Compared to the nafamostat mesylate group, the common heparin group exhibited significantly higher total cumulative infusion amounts of red blood cell suspension, plasma, platelet, FIB, hemocoagulase, and thromboplastin complex during the ECMO-assisted process, and the differences were statistically significant (all P<0.05). There was no statistically significant difference between the two groups of children in terms of time to ECMO assistance, membrane lung failure, loop thrombosis, embolism, and successful withdrawal rate (all P>0.05). Conclusion:Nafamostat mesylate can effectively reduce the risk of bleeding and minimize the requirement for blood product and coagulation substance infusions during traumatic ECMO assistance.

Objective:To evaluate the safety and efficacy of immunoadsorption with protein A column(PA-IA) in refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children.Methods:The clinical data of 8 children with anti-NMDAR encephalitis who failed to receive first-line treatment from January 2022 to June 2023 in PICU of Xi'an Children's Hospital were retrospectively collected.Clinical features,modified Rankin score (mRS),anti-NMDAR antibody titers in serum and cerebrospinal fluid(CSF),cells count in CSF,protein level in CSF,serum IgG,complement C3,C4 level were analyzed before and after immunoadsorption therapy. All adverse events that occurred during treatment were recorded in detail.Result:Among the 8 children,there were 5 males and 3 females,aged 5 to 12 years old,and each patient was immunized 6 to 10 times,and 75 times of PA-IA treatment were performed. The mRS score decreased in 8 children after PA-IA treatment. Blood IgG level,CSF cell number,protein level in CSF,blood complement C3 and C4 levels,and antibody titers related in blood and CSF were all lower than those before PA-IA treatment. The differences were all statistically significant ( P<0.001).During 75 times of treatment,only 1 case of membrane rupture occurred during treatment,the treatment was stopped and continued after the plasma separator was replaced,with no other adverse reactions. Conclusion:PA-IA could effectively improve the clinical symptoms and neurological function of children with refractory anti-NMDAR encephalitis with good safety,but its exact efficacy in children with anti-NMDAR encephalitis needs to be verified by prospective studies with larger samples.

Objective:To investigate the efficacy of nafamostat mesylate in traumatic extracorporeal membrane oxygenation (ECMO) therapy.Methods:Patients admitted to the intensive care units of Children's Hospital Affiliated to Xi'an Jiaotong University and Gansu Provincial Maternal and Child Health Hospital for ECMO-assisted cardiopulmonary support due to trauma from January 2021 to December 2024 were selected as the study subjects. Based on different anticoagulation strategies, patients were divided into the nafamostat mesylate group( n=11) and the common heparin group( n=10). The general conditions of the two groups were compared. In addition, differences in various clinical indicators during the ECMO-assisted process were compared, including white blood cell count (WBC), platelet count (PLT), hemoglobin level (Hb), hematocrit (HCT), prothrombin time(PT), activated partial thromboplastin time (APTT), thrombin time(TT), fibrinogen(FIB) and D-dimer. Furthermore，the differences in the total volume of component blood transfusions, coagulation substances, complications and prognosis between the two groups were compared. Results:No statistically significant differences were observed between the two groups regarding age, gender, weight, type of ECMO support, type of trauma, presence of active bleeding, or rate of surgical intervention. There were no statistically significant differences in WBC, PLT, Hb, HCT, PT, APTT, TT, FIB, and D-dimer between the two groups of patients prior to the initiation of ECMO support (all P>0.05). Compared with the common heparin group, children in the nafamostat mesylate group had lower PT[(21±6)s vs. (27±3)s; (20±4) vs. (28±5)], APTT[(68±8)s vs. (89±12)s; (64±15)s vs. (85±21)s], TT [(25±11)s vs. (31±13)s; (24±8)s vs. (35±6)s], and D-dimer[(5.8±1.1) μg/mL vs. (11.5±5.6) μg/mL; (4.2±1.8) μg/mL vs. (14.6±2.5) μg/mL],and higher FIB[(2.1±0.5) g/L vs. (1.6 ± 0.3) g/L; (2.4 ± 0.4) g/L vs. (1.3 ± 0.6) g/L] when ECMO assisted for 24 h and 72 h,the differences were all statistically significant(all P<0.05). Compared to the nafamostat mesylate group, the common heparin group exhibited significantly higher total cumulative infusion amounts of red blood cell suspension, plasma, platelet, FIB, hemocoagulase, and thromboplastin complex during the ECMO-assisted process, and the differences were statistically significant (all P<0.05). There was no statistically significant difference between the two groups of children in terms of time to ECMO assistance, membrane lung failure, loop thrombosis, embolism, and successful withdrawal rate (all P>0.05). Conclusion:Nafamostat mesylate can effectively reduce the risk of bleeding and minimize the requirement for blood product and coagulation substance infusions during traumatic ECMO assistance.

Anxiety disorders are one of the most epidemic and chronic psychiatric disorders. An incomplete understanding of anxiety pathophysiology has limited the development of highly effective drugs against these disorders. GPR17 has been shown to be involved in multiple sclerosis and some acute brain injury disorders. However, no study has investigated the role of GPR17 in psychiatric disorders. In a well-established chronic restraint stress (CRS) mouse model, using a combination of pharmacological and molecular biology techniques, viral tracing, in vitro electrophysiology recordings, in vivo fiber photometry, chemogenetic manipulations and behavioral tests, we demonstrated that CRS induced anxiety-like behaviors and increased the expression of GPR17 in basolateral amygdala (BLA) glutamatergic neurons. Inhibition of GPR17 by cangrelor or knockdown of GPR17 by adeno-associated virus in BLA glutamatergic neurons effectively improved anxiety-like behaviors. Overexpression of GPR17 in BLA glutamatergic neurons increased the susceptibility to anxiety-like behaviors. What's more, BLA glutamatergic neuronal activity was required for anxiolytic-like effects of GPR17 antagonist and GPR17 modulated anxiety-like behaviors via BLA to ventral hippocampal CA1 glutamatergic projection. Our study finds for the first and highlights the new role of GPR17 in regulating anxiety-like behaviors and it might be a novel potential target for therapy of anxiety disorders.

Coagulation factor ⅩⅢ (FⅩⅢ) deficiency is a rare disease that is easily overlooked because routine coagulation tests do not reflect its deficiency. FⅩⅢ deficiency is divided into hereditary FⅩⅢ deficiency and acquired FⅩⅢ deficiency. The diagnosis of FⅩⅢ deficiency requires testing for FⅩⅢ activity and antigen, with confirmation through genetic testing. Due to the instability of fibrin clots caused by FⅩⅢ deficiency, the clinical features of FⅩⅢ deficiency include umbilical cord bleeding, soft tissue hematoma, recurrent miscarriage, cerebral hemorrhage, and delayed wound healing. Acquired FⅩⅢ deficiency can be caused by various reasons, and this article introduces a case of acquired FⅩⅢ deficiency in a patient after hip replacement surgery due to long-term use of sodium valproate.

Objective:To predict the incidence, prevalence, and mortality of dementia in China from 2020 to 2040.Methods:The age-standardized incidence rate (ASIR), incidence number, age-standardized prevalence rate (ASPR), prevalence number, age-standardized mortality rate (ASMR), and death number of dementia in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study (GBD) database. We used the overall change rate and estimated annual percentage change (EAPC) to describe the epidemic situation of dementia and compared the trend of dementia between genders. A T-test was used to determine whether EAPC was statistically significant. Every five years, we divided the age into 17 groups to analyze the incidence, prevalence, and mortality of dementia. The prophet model predicted ASIR, ASPR, ASMR, incidence, prevalence, and death from dementia in China from 2020 to 2040.Results:The ASIR, ASPR, and ASMR of dementia showed an increasing trend from 1990 to 2019, with an average annual increase of 0.33%, 0.66%, and 0.15% ( t=10.13, 14.49 and 3.62, all P<0.05). The ASIR, ASPR, and ASMR in males increased faster annually than in females. In 2019, the number of incidence, prevalence, and death from dementia in groups aged≥80 years was the highest among all age groups (685 057 cases, 5 772 861 cases, and 217 827 cases). Prediction results of the prophet model showed that the ASIR, ASPR, and ASMR of dementia were further increased in China from 2020 to 2040, with an average annual increase of 0.55%, 0.78%, and 0.06% ( t=177.63, 161.21, and 7.91, all P<0.05). In 2040, the ASIR, ASPR, and ASMR will reach 117.72/10 5, 940.98/10 5, and 23.64/10 5, respectively. In addition, the number of incidence, prevalence, and death from dementia will show an upward trend from 2020 to 2040. In 2040, the incidence, prevalence, and death will reach 3 334 770 cases, 25 303 146 cases, and 590 138 cases, respectively. Conclusion:From 2020 to 2040, the ASIR, ASPR, ASMR, number of incident cases, number of prevalent cases, and number of deaths due to dementia in China will continue to grow.