Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective:To investigate the clinical manifestations，etiology/triggers，treatment，and prognosis of children with cerebral venous sinus thrombosis（CVST）.Methods:A retrospective analysis was conducted on 36 children with CVST hospitalized at the Affiliated Children's Hospital of Xiangya School of Medicine,Central South University（Hunan Children's Hospital）from May 2014 to January 2024.A centralized telephone follow-up was performed in May 2024，and clinical data including symptoms，imaging findings，treatments，and outcomes were collected.According to the prognosis,the children were divided into favorable-prognosis group and poor-prognosis group,and the differences of clinical characteristics between the two groups were compared.The univariate Logistic regression was applied to identify factors associated with prognosis.Results:Among the 36 cases,there were 29 males and 7 females,ranging in age from 1 month to 13 years and 3 months,with a median age of 4.6(1.0,8.3) years.The common clinical manifestations included headache（24/25，96.0%），consciousness disorder（25/36，69.4%），vomiting（22/36，61.1%），seizures（14/36，38.9%），limb dysfunction（11/36，30.6%）.The leading etiologies were infection（14/36，38.9%），head trauma（8/36，22.2%），and tumors/chemotherapy（6/36，16.7%）.All 36 children underwent MRI+MRV examination of the head,and all of them had different degrees of CVST,the most commonly involved site was transverse sinus (28/36,77.8%).The favorable-prognosis group（ n=18）included 16 patients receiving anticoagulation and 2 trauma cases without anticoagulation.The poor-prognosis group（ n=18）comprised 9 anticoagulated and 9 non-anticoagulated patients.There were no significant differences in age,sex,clinical manifestations,etiology/inducement and thrombus site between the two groups ( P>0.05).However,the proportion of anticoagulant therapy in the favorable-prognosis group was higher than that in the poor-prognosis group(88.9% vs 50.0%).Among the 25 children receiving anticoagulant therapy,16 had a good prognosis (64.0%),while among the 11 children receiving no anticoagulant therapy,only 2 had a good prognosis (18.2%).The prognosis of children receiving anticoagulant therapy was better than that of those receiving no anticoagulant therapy.The difference was statistically significant ( P<0.05).Fourteen children were admitted with intracranial hemorrhage,with 8 receiving anticoagulant therapy (7 with good prognosis,accounting for 87.5%) and 6 not receiving anticoagulant therapy (only 1 with good prognosis,accounting for 12.5%).The prognosis of children receiving anticoagulant therapy was better than that of those receiving no anticoagulant therapy,and the difference was statistically significant ( P=0.026),with no increasing in intracranial hemorrhage after anticoagulant therapy.Univariate Logistic regression analysis showed that inducement/etiology,intracranial hemorrhage before treatment and prognosis were not related（ P >0.05），but anticoagulation treatment was associated with favorable outcomes（ OR=0.125，95% CI 0.017-0.614, P=0.009）. Conclusion:Infection is the primary etiology of pediatric CVST，with headache，lethargy，and vomiting as key symptoms.Transverse sinus is the most commonly involved site.Children suspected of CVST should be examined by MRI/MRV as soon as possible,and early anticoagulation therapy should be given after a clear diagnosis,so as to improve the prognosis.

Objective To explore the impact of integrated traditional Chinese and Western medicine on the overall survival(OS)of patients with biliary tract carcinoma(BTC),and to analyze the related factors affecting the OS of patients with BTC,so as to provide accurate prognosis assessment for clinical diagnosis and treatment.Methods The medical records of 198 patients with BTC in Henan Provincial Hospital of Traditional Chinese Medicine from February 2018 to October 2023 were retrospectively analyzed.The Cox proportional hazards model was utilized to analyze the independent prognostic factors affecting the OS of BTC patients.Survival curves were constructed using the Kaplan-Meier method,and the Log-rank test was employed to compare median OS differences among various groups.Results A total of 116 patients with BTC were included.There were 59 cases(50.86％)in the Western medicine group,with a median OS of(14±2.77)months,and the 1-,2-and 3-year OS rates were 81.36％,61.02％and 46.11％,respectively.There were 57 cases(49.14％)in the integrated traditional Chinese and Western medicine group,with a median OS of(29±3.91)months,and the 1-,2-and 3-year OS rates were 82.32％,67.64％and 58.00％,respectively.There was a statistically significant difference in survival time between the two groups(P=0.038).Univariate analysis indicated that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy and integrated traditional Chinese and Western medicine were significantly correlated with OS in BTC patients(all P＜0.05).Multivariate analysis revealed that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine had significant effects on the OS of patients with BTC(all P＜0.05).Conclusion The median OS of the traditional Chinese and Western medicine groups was significantly longer than that of the Western medicine group,and the long-term OS rate of the patients was significantly better than that of the Western medicine group.Age,clinical stage,surgery,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine are independent prognostic factors affecting OS in patients with BTC.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

OBJECTIVES: To investigate the potential circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) immune regulatory network in childhood allergic asthma by analyzing microarray datasets. METHODS: GEO database was used to obtain the datasets of circRNA, miRNA, and mRNA from children with allergic asthma and healthy controls. The Limma package was used to identify differentially expressed circRNA (DEcircRNA), miRNA (DEmiRNA), and mRNA (DEmRNA). ENCORI and other tools were used to predict and construct the regulatory network of endogenous RNA. The DAVID database was used to perform GO and KEGG enrichment analyses, and CIBERSORT and Pearson were used to identify genes associated with immune cell infiltration. RESULTS: A total of 130 DEcircRNAs, 40 DEmiRNAs, and 802 DEmRNAs were identified between the asthma and control groups, and a regulatory network consisting of 12 circRNAs, 7 miRNAs, and 75 mRNAs was established. The GO analysis showed that the differentially expressed genes were mainly involved in the regulation of growth and development, and the KEGG analysis showed that they were mainly involved in the mTOR signaling pathway. The CIBERSORT analysis showed that compared with the control group, the asthma group had higher percentages of CD8⁺ T cells and resting NK cells and lower percentages of resting CD4⁺ memory T cells and activated mast cells. In addition, the Pearson correlation analysis identified six key mRNAs that were positively correlated with immune cell infiltration. CONCLUSIONS The ceRNA immune regulatory network constructed in this study provides a basis for research on the mechanism of childhood allergic asthma and potential therapeutic targets.
Humans ; Asthma/genetics* ; RNA, Circular/physiology* ; MicroRNAs/physiology* ; Child ; Gene Regulatory Networks ; RNA, Messenger/physiology* ; RNA/physiology* ; Male ; Female ; Child, Preschool

Objective:To investigate the clinical manifestations，etiology/triggers，treatment，and prognosis of children with cerebral venous sinus thrombosis（CVST）.Methods:A retrospective analysis was conducted on 36 children with CVST hospitalized at the Affiliated Children's Hospital of Xiangya School of Medicine,Central South University（Hunan Children's Hospital）from May 2014 to January 2024.A centralized telephone follow-up was performed in May 2024，and clinical data including symptoms，imaging findings，treatments，and outcomes were collected.According to the prognosis,the children were divided into favorable-prognosis group and poor-prognosis group,and the differences of clinical characteristics between the two groups were compared.The univariate Logistic regression was applied to identify factors associated with prognosis.Results:Among the 36 cases,there were 29 males and 7 females,ranging in age from 1 month to 13 years and 3 months,with a median age of 4.6(1.0,8.3) years.The common clinical manifestations included headache（24/25，96.0%），consciousness disorder（25/36，69.4%），vomiting（22/36，61.1%），seizures（14/36，38.9%），limb dysfunction（11/36，30.6%）.The leading etiologies were infection（14/36，38.9%），head trauma（8/36，22.2%），and tumors/chemotherapy（6/36，16.7%）.All 36 children underwent MRI+MRV examination of the head,and all of them had different degrees of CVST,the most commonly involved site was transverse sinus (28/36,77.8%).The favorable-prognosis group（ n=18）included 16 patients receiving anticoagulation and 2 trauma cases without anticoagulation.The poor-prognosis group（ n=18）comprised 9 anticoagulated and 9 non-anticoagulated patients.There were no significant differences in age,sex,clinical manifestations,etiology/inducement and thrombus site between the two groups ( P>0.05).However,the proportion of anticoagulant therapy in the favorable-prognosis group was higher than that in the poor-prognosis group(88.9% vs 50.0%).Among the 25 children receiving anticoagulant therapy,16 had a good prognosis (64.0%),while among the 11 children receiving no anticoagulant therapy,only 2 had a good prognosis (18.2%).The prognosis of children receiving anticoagulant therapy was better than that of those receiving no anticoagulant therapy.The difference was statistically significant ( P<0.05).Fourteen children were admitted with intracranial hemorrhage,with 8 receiving anticoagulant therapy (7 with good prognosis,accounting for 87.5%) and 6 not receiving anticoagulant therapy (only 1 with good prognosis,accounting for 12.5%).The prognosis of children receiving anticoagulant therapy was better than that of those receiving no anticoagulant therapy,and the difference was statistically significant ( P=0.026),with no increasing in intracranial hemorrhage after anticoagulant therapy.Univariate Logistic regression analysis showed that inducement/etiology,intracranial hemorrhage before treatment and prognosis were not related（ P >0.05），but anticoagulation treatment was associated with favorable outcomes（ OR=0.125，95% CI 0.017-0.614, P=0.009）. Conclusion:Infection is the primary etiology of pediatric CVST，with headache，lethargy，and vomiting as key symptoms.Transverse sinus is the most commonly involved site.Children suspected of CVST should be examined by MRI/MRV as soon as possible,and early anticoagulation therapy should be given after a clear diagnosis,so as to improve the prognosis.

Parkinson's disease(PD)is one of the most common neurodegenerative disorders.Recent evidence implicates pyroptosis as one of the pathogenic mechanisms in central nervous system disorders,although its specific mechanisms remain unclear.In this study,SH-SY5Y cells were transfected with py-roptosis-related proteins GSDME full-length(GSDME-F)or GSDME-N terminal(GSDME-N)plasmids revealed that GSDME-N significantly reduced mitochondrial membrane potential(P＜0.0001).To inves-tigate the mechanism by which GSDME mediates mitochondrial dysfunction,Western blotting analysis demonstrated that transfection with GSDME-N plasmids significantly increased BAX expression and en-hanced its translocation to mitochondria in both HEK 293T and SH-SY5Y cells(P＜0.05).SH-SY5Y cells treated with varying concentrations of rotenone(ROT)exhibited GSDME cleavage,elevated BAX expression(P＜0.05),increased mitochondrial BAX aggregation(P＜0.05),and reduced mitochondrial membrane potential(P＜0.01),as confirmed by Western blotting and JC-1 staining.Concurrently,MTT assays assessing cell viability and lactate dehydrogenase(LDH)release assays indicated that ROT in-duced these processes prior to pyroptosis.Furthermore,in a ROT-induced mouse PD model,ROT trig-gered GSDME cleavage,enhanced BAX expression,caused dopaminergic neuronal damage,and induced motor deficits.In summary,this study demonstrates that GSDME-N exacerbates mitochondrial damage and increases cytotoxicity by upregulating BAX expression and facilitating its mitochondrial translocation.This study provides novel insights into the role of GSDME in PD pathogenesis and suggests potential avenues for therapeutic intervention.

Objective To explore the impact of integrated traditional Chinese and Western medicine on the overall survival(OS)of patients with biliary tract carcinoma(BTC),and to analyze the related factors affecting the OS of patients with BTC,so as to provide accurate prognosis assessment for clinical diagnosis and treatment.Methods The medical records of 198 patients with BTC in Henan Provincial Hospital of Traditional Chinese Medicine from February 2018 to October 2023 were retrospectively analyzed.The Cox proportional hazards model was utilized to analyze the independent prognostic factors affecting the OS of BTC patients.Survival curves were constructed using the Kaplan-Meier method,and the Log-rank test was employed to compare median OS differences among various groups.Results A total of 116 patients with BTC were included.There were 59 cases(50.86％)in the Western medicine group,with a median OS of(14±2.77)months,and the 1-,2-and 3-year OS rates were 81.36％,61.02％and 46.11％,respectively.There were 57 cases(49.14％)in the integrated traditional Chinese and Western medicine group,with a median OS of(29±3.91)months,and the 1-,2-and 3-year OS rates were 82.32％,67.64％and 58.00％,respectively.There was a statistically significant difference in survival time between the two groups(P=0.038).Univariate analysis indicated that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy and integrated traditional Chinese and Western medicine were significantly correlated with OS in BTC patients(all P＜0.05).Multivariate analysis revealed that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine had significant effects on the OS of patients with BTC(all P＜0.05).Conclusion The median OS of the traditional Chinese and Western medicine groups was significantly longer than that of the Western medicine group,and the long-term OS rate of the patients was significantly better than that of the Western medicine group.Age,clinical stage,surgery,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine are independent prognostic factors affecting OS in patients with BTC.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.