Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Objective To analyze the application of flipped classroom in the practical teaching of rehabilitation assessment courses for rehabilitation therapy majors,and to explore a new teaching method for rehabilitation therapy.Methods Eighty students majoring in rehabilitation therapy from the Department of Rehabilitation Medicine of Guangzhou Xinhua University in grade 2020 were selected as the research objects.They were assigned into observation group or control group according to the random number table method,with 40 cases in each group.The observation group adopted the flip classroom teaching mode,and the rehabilitation assessment course teaching based on flipped classroom was carried out,while the control group adopted the traditional teaching mode.The students'theoretical and operational assessment results,teaching effect,and teaching model satisfaction were analyzed.Results No statistically significant differences were found in theoretical test scores between the two student groups(by gender/course).The students in the observation group had higher theoretical scores[(80.25±11.65 vs 72.50±14.28)score].The observation group showed significantly higher satisfaction scores than the control group across all three dimensions:classroom learning enthusiasm,teacher-student interaction,and overall teaching satisfaction.(P<0.05).Conclusion The application of flipped classroom in the rehabilitation therapy teaching is helpful to improve the professional theoretical level of students,and to a certain extent,it is beneficial to improve the professional level of teachers.

Objective: To investigate the correlation of emotional and behavioral problems with sleep problems in children with cerebral palsy, so as to provide reference for intervention of emotional and behavioral problems in children. Methods: A cross sectional survey was conducted, and 402 children aged 6-18 with cerebral palsy who were adopted by social welfare institutions in Guangzhou City from January 2023 to January 2024 were selected to investigate their full time nurses. The Parents Strengths and Difficulties Questionnaire (SDQ) was used to assess the emotional and behavioral problems of children with cerebral palsy, and the Children s Sleep Habits Questionnaire (CSHQ) was used to assess sleep problems. Multiple linear regression analysis was used to analyze the correlation between the sleep problem of children with cerebral palsy and the emotional and behavioral problems. Results: The prevalence of emotional and behavioral difficulties among children with cerebral palsy was 15.7%. The median sleep problem score of children with emotional and behavioral problems [37.0(36.0, 41.0)] was significantly higher than that of children without emotional and behavioral [35.0(34.0, 36.0)] ( Z =-5.74, P <0.01). The results of multiple linear regression analysis showed that after adjusting covariables such as age, gender, cerebral palsy classification, language retardation, visual impairment and epilepsy, the total sleep problem score of children with cerebral palsy was positively correlated with the total difficulty score ( β= 0.28, 95%CI =0.17-0.34, P <0.05). Conclusions Sleep problems in children with cerebral palsy are associated with emotional and behavioral difficulties. Understanding of the management of sleep problems in children with cerebral palsy should be enhanced to reduce the incidence of emotional and behavioral problems in children with cerebral palsy.

Purpose To explore the predictive value of hepatosplenic hemodynamic indexes obtained by dual-energy CT combined with clinical features in non-invasive assessment of high-risk esophageal varices(EV)in cirrhosis.Materials and Methods We retrospectively collected 93 patients with cirrhosis from March 2022 to May 2023 in Zengcheng Branch of Nanfang Hospital.All patients underwent epigastric enhanced energy spectrum scan and gastroscopy.EV severity as assessed by gastroscopy(none,EV0;mild,EV1;medium,EV2;severe,EV3)were divided into low-risk EV group(EV0 and EV1)and high-risk EV group(EV2 and EV3).Age,gender,Child-Pugh grade,ascites and platelet of the two groups were collected,and dual-energy CT parameters including liver and spleen volume,mean iodine content in liver and spleen and liver and spleen iodine volume were measured.The difference of parameters between the low-risk EV and the high-risk EV group were analyzed,and the model was constructed by Logistic regression analysis.Receiver operating characteristic curve was used to evaluate the diagnostic performance of the model for high-risk EV.Results There were significant differences in age,Child-Pugh grade,ascites,platelet,liver and spleen volume,liver and spleen iodine volume between low-risk EV and high-risk EV groups(Z/χ2=-5.921-16.343,all P<0.05).Ascites,platelet,liver and spleen volume,liver and spleen iodine volume were included in multivariate regression analysis to construct regression models,and the results showed that spleen iodine volume(OR=1.002,P<0.001),ascites(OR=5.319,P=0.009),platelet(OR=0.99,P=0.062)were independent risk factors for predicting the high risk of EV.Hosmer-Lemeshow test showed that the regression model fit the observed values well(P=0.303),with accuracy of 83.9%,sensitivity of 78.6%,specificity of 88.2%,positive prediction rate of 84.6%and negative prediction rate of 83.3%.The area under the curve of this regression model was 0.894.Conclusion Spleen iodine content based on dual-energy CT,platelet and ascites can noninvasively predict high-risk EV.

Purpose To explore the predictive value of hepatosplenic hemodynamic indexes obtained by dual-energy CT combined with clinical features in non-invasive assessment of high-risk esophageal varices(EV)in cirrhosis.Materials and Methods We retrospectively collected 93 patients with cirrhosis from March 2022 to May 2023 in Zengcheng Branch of Nanfang Hospital.All patients underwent epigastric enhanced energy spectrum scan and gastroscopy.EV severity as assessed by gastroscopy(none,EV0;mild,EV1;medium,EV2;severe,EV3)were divided into low-risk EV group(EV0 and EV1)and high-risk EV group(EV2 and EV3).Age,gender,Child-Pugh grade,ascites and platelet of the two groups were collected,and dual-energy CT parameters including liver and spleen volume,mean iodine content in liver and spleen and liver and spleen iodine volume were measured.The difference of parameters between the low-risk EV and the high-risk EV group were analyzed,and the model was constructed by Logistic regression analysis.Receiver operating characteristic curve was used to evaluate the diagnostic performance of the model for high-risk EV.Results There were significant differences in age,Child-Pugh grade,ascites,platelet,liver and spleen volume,liver and spleen iodine volume between low-risk EV and high-risk EV groups(Z/χ2=-5.921-16.343,all P<0.05).Ascites,platelet,liver and spleen volume,liver and spleen iodine volume were included in multivariate regression analysis to construct regression models,and the results showed that spleen iodine volume(OR=1.002,P<0.001),ascites(OR=5.319,P=0.009),platelet(OR=0.99,P=0.062)were independent risk factors for predicting the high risk of EV.Hosmer-Lemeshow test showed that the regression model fit the observed values well(P=0.303),with accuracy of 83.9%,sensitivity of 78.6%,specificity of 88.2%,positive prediction rate of 84.6%and negative prediction rate of 83.3%.The area under the curve of this regression model was 0.894.Conclusion Spleen iodine content based on dual-energy CT,platelet and ascites can noninvasively predict high-risk EV.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.

Objective To observe the effects of Jianpi Liqi Huashi Prescription on hepatocyte injury,oxidative stress and nitrative stress in mice with non-alcoholic steatohepatitis(NASH);To explore its mechanism in the treatment of NASH.Methods Totally 32 male C57BL/6J mice were randomly divided into control group,model group and TCM low-and high-dosage groups,with 8 mice in each group.The control group was fed with ordinary diet,and the other groups were fed with high-fat diet,for consecutive 16 weeks.Starting from the 13th week,the control group and model group were given 0.4%CMC-Na solution by intragastric administration and the TCM groups were given corresponding doses of drugs by intragastric administration,respectively.Biochemical instrument was used to detect serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)contents,HE staining and oil red O staining were used to detect liver histopathology,triglyceride(TG)content and myeloperoxidase(MPO)activity in liver tissue were detected through test kit.immunofluorescence staining was used to detect positive expression of CD11b in liver tissue,the mRNA expressions of NOX1 and NCF1 were detected by RT-PCR,and the protein expressions of inducible nitric oxide synthase(iNOS)and 3-nitrotyrosine(3-NT)in liver tissue were detected by Western blot.Results Compared with the control group,the hepatocytes in the model group showed diffuse steatosis,hepatocyte swelling and inflammatory cell infiltration;a large number of fat droplets were formed by oil red O staining;serum ALT and AST contents significantly increased(P<0.05),the TG content and MPO activity in liver tissue significantly increased(P<0.05);the positive expression of CD11b in liver tissue increased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly increased(P<0.05);the expressions of iNOS and 3-NT protein in liver tissue significantly increased(P<0.05).Compared with the model group,the degree of liver steatosis,the level of inflammatory cell infiltration and the number of lipid droplets in TCM groups decreased significantly;serum ALT and AST contents significantly decreased(P<0.05);the TG contents and MPO activity in liver tissue significantly decreased(P<0.05);the positive expression of CD11b in liver tissue decreased;the mRNA expressions of NOX1 and NCF1 in liver tissue significantly decreased(P<0.05);the expression of 3-NT protein in liver tissue significantly decreased(P<0.05);the expression of iNOS protein in liver tissue of mice in TCM high-dosage group significantly decreased(P<0.05).Conclusion Jianpi Liqi Huashi Prescription may relieve liver cell damage,lipid deposition and inflammation in NASH mice by alleviating oxidative stress and nitrative stress in the liver,and play a role in the treatment of NASH.

Objective: To under the prevalence of malnutrition and its associated factors in school aged children with cerebral palsy, so as to provide a basis for relevant departments to formulate targeted policies. Methods: From July to August 2023, the researchers selected 333 children with cerebral palsy and 960 children with other diseases aged 6-18 years who were residents of a social welfare institution in Guangzhou, China. Their height and weight were measured and a nutritional status analysis was carried out using a cluster sampling method. Multivariate Logistic analysis was performed to analyze the relative factors and malnutrition status of school aged children with cerebral palsy. Results: The prevalence of growth retardation among school aged children with cerebral palsy was 74.5%, with rates of stunting, normal nutrition status, and overweight/obesity being 17.7%, 7.2%, and 0.6%, respectively. The results of the univariate analysis revealed statistically significant differences in the detection rate of malnutrition among school aged children with cerebral palsy based on gender, gross motor function classification system (GMFCS) grading, and the presence of swallowing disorders ( χ 2=6.02, 15.23, 32.16, P <0.05). The results of the multivariate Logistic regression analysis showed that gender ( OR=0.37, 95%CI =0.15-0.91), dysphagia (OR=4.10, 95%CI =1.39-12.12), and GMFCS classification ( OR=1.45, 95%CI =1.04-3.01) were influencing factors of malnutrition ( P <0.05). Conclusions The detection rate of malnutrition among children and adolescents with cerebral palsy in welfare institutions was found to be relatively high, and influenced by various factors. Corresponding nutritional interventions should be developed and implemented based on the risk factors of malnutrition in school aged children with cerebral palsy to improve their nutritional status.