Objective To investigate the influence of comorbidities on the prognosis of patients with status epilepticus， to develop Improved Comorbidity Burden Index （ICBI） based on Comorbidity Burden Index （CBI）， and to analyze the practicality of ICBI in assessing nonconvulsive status epilepticus in western China.Methods A total of 396 patients with status epilepticus who were treated in Department of Neurology， Intensive Care Unit， and Emergency Department， West China Hospital， Sichuan University， from December 2016 to December 2022 were enrolled， and all patients met the latest diagnostic criteria for status epilepticus issued by the International League Against Epilepsy （2015 edition）. SPSS 22.0 was used to perform a statistical analysis， and a Logistic regression analysis was used to investigate the influencing factors for in-hospital death and poor prognosis （with a Glasgow Outcome Scale score of 1-3）. CBI score was modified into ICBI score， with the addition of three comorbidities （immune system disorder， thyroid dysfunction， and hypoproteinemia） and consolidation of overlapping items， and the total score was calculated with each comorbidity contributing 1 score. The MedCalc-generated receiver operating characteristic （ROC） curve was used to analyze predictive value， and the area under the ROC curve （AUC） was used to reflect the diagnostic value of ICBI scale.Results Among the 396 patients with status epilepticus included in the study， 43 （10.9%） died in hospital and 114 （28.8%） had a poor prognosis. Digestive system diseases， respiratory system diseases， kidney and urinary system diseases， electrolyte/acid-base imbalance， infection， and immune system disorders were risk factors for in-hospital death of patients with status epilepticus. Digestive system diseases， respiratory system diseases， kidney and urinary system diseases， electrolyte/acid-base imbalance， hypoglycemia/hyperglycemia， infection， coagulation and blood disorders， nervous system disease， cardiovascular diseases， musculoskeletal disorders， and immune system disorders were risk factors for poor prognosis in patients with status epilepticus. The ROC curve analysis showed that ICBI>3 had an AUC of 0.914 in predicting in-hospital death， with a specificity of 71.37% and a sensitivity of 97.67% （P<0.000 1）， and ICBI>3 had an AUC of 0.882 in predicting poor prognosis， with a specificity of 81.56% and a sensitivity of 79.82% （P<0.000 1）. There were 327 patients with convulsive status epilepticus， among whom 41 patients died， and ICBI>3 had an AUC of 0.915 in predicting in-hospital death （P<0.000 1）. There were 100 patients with a poor prognosis， and ICBI>3 had an AUC of 0.867 in predicting poor prognosis （P<0.000 1）.Conclusion The in-hospital mortality rate is 10.9% in patients with status epilepticus in Sichuan， China， and ICBI>3 has a certain value in predicting in-hospital death and poor prognosis in patients with status epilepticus. There is no significant difference in ICBI score between convulsive status epilepticus and nonconvulsive status epilepticus.
Prognosis

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective To analyze the changes of vitamin D in children with Henoch-Schonlein purpura(HSP).Methods 130 children with HSP from Kunming Children's Hospital between July 2022-July 2023 were selected as the study subjects and 100 healthy children were selected during the same period as the control group.The blood samples were collected from the children with HSP and the healthy children.The content of vitamin D was measured by Kunming Kingmed Institute for Clinical Laboratory.Results The content of 25(OH)D in children with HSP was lower than that in healthy children,and the difference was statistically significant(P<0.01).The proportion of vitamin D insufficiency in children with HSP was higher than that in healthy children,and the difference was statistically significant(P<0.01).Conclusion The children with HSP are prone to vitamin D insufficiency.Vitamin D supplementation may provide a new method for the treatment of HSP.

Histone acetylation and methylation can affect chromatin conformation and regulate a variety of biological activities.Abnormal histone acetylation and methylation modifications are related to the occurrence and development of a variety of oral diseases.Histone acetylation and methylation increase or decrease in an orderly manner to regulate the development of teeth.Fluoride ions can destroy the balance between histone acetylation and methylation,which may be related to the occurrence of dental fluorosis.In addition,histone acetylation and methylation are involved in the regula-tion of oral inflammatory diseases.In the inflammatory microenvironment,the expression of histone acetyltransferase GCN5 decreases,and the expression of Dickkopf 1(DKK1)decreases,activating the Wnt/β-catenin pathway and ulti-mately inhibiting the osteogenic differentiation of periodontal ligament stem cells.Enhancer of zeste homolog 2(EZH2)and H3K27me3 levels were decreased in inflamed dental pulp tissues and cells.EZH2 inhibition inhibited the expres-sion of interleukin(IL)-1b,IL-6 and IL-8 in human dental pulp cells under inflammatory stimulation.Histone acetyla-tion/methylation modifications can interact with multiple signaling pathways to promote the occurrence and development of oral tumors and are related to the high invasiveness of salivary gland tumors.Small molecule drugs targeting histone acetylation and methylation-related enzymes can regulate the level of histone methylation/acetylation and have shown po-tential in the treatment of oral and maxillofacial diseases.For example,the histone deacetylase inhibitor vorinostat can inhibit the secretion of inflammation-related cytokines;it also promotes the maturation of odontoblasts and the formation of dentin-related matrix,demonstrating its potential in pulp preservation.Understanding the role of histone acetylation/methylation modifications in the occurrence and development of oral diseases will help promote research on epigenetic modifications in oral diseases and provide new perspectives for disease diagnosis and treatment.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To study the clinical efficacy and safety of dapagliflozin combined with sacubitril-valsartan in the treatment of heart failure with preserved ejection fraction (HFpEF).Methods A total of 128 patients with HFpEF hospitalized in the cardiovascular medicine department of this hospital from March to December 2022 were selected as the study subjects and divided into the observation group and control group by the random number table method,64 cases in each group.The control group was given the conventional an-ti-heart failure therapy and orally took sacubitril-valsartan,and the observation group took the combined ap-plication of dapagliflozin on the basis of the control group.The continuous treatment lasted for 12 months. The left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) were com-pleted by the cardiac color Doppler ultrasound determination in 3,6,12 months after treatment,the blood was collected for detecting NT-poBNP and 6 min walking distance (6MWD) determination was completed.The outpatient follow up was conducted monthly,the follow up contents contained the adverse reactions and major adverse cardio vascular event (MACE) events.Results After 3-month treatment,the NT-proBNP level in the two groups was decreased compared with before treatment,moreover the observation group was lower than the control group,and the differences were statistically significant (P<0.05).Compared with before treat-ment,LVEDd after 3-month treatment in the two groups was decreased compared with before treatment,LVEF was increased compared with before treatment,and the differences were statistically significant (P<0.05).LVEDd after 6-,12-month treatment in the observation group was lower than that in the control group,LVEF was higher than that in the control group,and the differences were statistically significant (P<0.05).6MWD after 3-month treatment in the two groups was increased compared with before treatment,and the difference was statistically significant (P<0.05).6MWD after 6-,12-month treatment in the observation group was higher than that in the control group,and the difference was statistically significant (P<0.05). The re-admission rate due to heart failure and MACE total occurrence rate in the observation group were low-er than those in the control group (9.38％ vs. 23.44％,12.50％ vs. 26.50％,P<0.05),and the adverse re-actions occurrence rates had no statistical difference between the two groups (P>0.05).Conclusion Dapagliflozin combined with sacubitril-valsartan could significantly improve the cardiac function in elderly patients with HFpEF,reduce the occurrence rate of MACE,moreover has good safety.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Aim To investigate the regulatory effects of chlorogenic acid(CGA)on mitochondrial autophagy and inflammation in ox-LDL induced foam cells through PINK1/Parkin signaling pathway.Methods RAW264.7 macrophages were divided into the control group,model group,CGA-L group,CGA-M group,CGA-H group and CGA-H+Mdi group.Oil red O method was used to identify cell foam.The intervention concentration of CGA was determined by CCK-8 meth-od.The mitochondrial structure was observed by trans-mission electron microscope.The expression of IL-1 β,IL-18 and IFN-γ was detected by ELISA.The expres-sion of genes and proteins associated with PINK1/Par-kin mitochondrial autophagy pathway was detected by qRT-PCR and immunofluorescence labeling.Results Oil red O staining showed that the foam cell model was successfully prepared.Compared with the model group,mitochondrial damage was significantly reduced after CGA intervention at different concentrations,and the expressions of PINK1,Parkin,p-Parkin,PHB2 and LC3 Ⅱ were induced,while the expression of TOMM20 was inhibited.The expressions of IL-1 β,IL-18 and IFN-γ decreased(P＜0.05 or P＜0.01).Compared with the CGA-H group,the CGA-H+Mdi group significantly increased mitochondrial damage,in-hibited the expression of PINK1,Parkin,p-Parkin,PHB2,LC3 Ⅱ,induced the expression of TOMM20,and enhanced the expression of IL-1 β,IL-18,IFN-γ(P＜0.01).Conclusions CGA can induce mitochon-drial autophagy in foam cells by regulating PINK1/Par-kin pathway and inhibit the overexpression of pro-in-flammatory factors IL-1 β,IL-18 and IFN-y,which may be one of the anti-atherosclerosis mechanisms of CGA.

Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.