OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6- trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （P＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （P＜0.05）； the improvement effect of Asp-H group was more significant （P＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （P＜0.05）. CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.

OBJECTIVE To investigate the effects and mechanism of asperuloside （Asp） on the pyroptosis of intestinal epithelial cells in rats with ulcerative colitis （UC）. METHODS The male SD rats were randomly divided into Control group， model group （UC group）， ASP low-dose and high-dose groups [Asp-L， Asp-H groups， Asp 35， 70 mg/（kg·d）]， ASP high-dose group+AMPK inhibitor Compound C group [Asp-H+Compound C group， Asp 70 mg/（kg·d）+Compound C 0.2 mg/（kg·d）]， with 12 rats in each group. Except for Control group， the other groups were injected with 50% ethanol （0.25 mL）+5% 2，4， 6- trinitrobenzene sulfonic acid solution （2 mL/kg） into the intestinal cavity to construct UC model. After modeling， the rats in each drug group were given corresponding drug solution by gavage or （and） tail vein injection， once a day， for 14 consecutive days. After the last administration， the weight of rats in each group was measured， and the length of their colons was measured； disease activity index （DAI） score and colonic mucosal damage index （CMDI） score were performed， and the serum levels of inflammatory factors （interleukin-18， -1β， -6） were detected. The pathological changes of the colon tissue were observed. The expressions of pyroptosis-related proteins [caspase-1， gasdermin D （GSDMD）] in colon tissue， and pathway-related proteins such as adenosine monophosphate-activated protein kinase （AMPK）， thioredoxin-interacting protein （TXNIP）， NOD-like receptor protein 3 （NLRP3） and apoptosis-associated speck-like protein containing a CARD （ASC） were all detected. RESULTS Compared with Control group， the colon tissue structure of rats in UC group was damaged， with obvious infiltration of inflammatory cells and edema. Their body weight， colon length and phosphorylation level of AMPK protein were significantly reduced or shortened； DAI and CMDI scores， serum levels of inflammatory factors， and the protein expressions of caspase-1， GSDMD， TXNIP， NLRP3 and ASC in colon tissue were increased or upregulated significantly （P＜0.05）. Compared with UC group， the pathological damage of colon tissue in rats was relieved in Asp-L and Asp-H groups， and all quantitative indicators were significantly improved （P＜0.05）； the improvement effect of Asp-H group was more significant （P＜0.05）. Compound C could significantly reverse the improvement effect of high-dose of Asp on the above indicators in UC rats （P＜0.05）. CONCLUSIONS Asp can improve inflammatory damage in colon tissue and inhibit pyroptosis of intestinal epithelial cells in UC rats， which is associated with the activation of AMPK and inhibition of TXNIP/NLRP3 signaling pathway.

Objective:To systematically search and evaluate risk prediction models for ventilator-associated pneumonia (VAP) of ICU in order to provide references for developing higher-quality VAP risk prediction models.Methods:Relevant literature was retrieved from databases including China Biology Medicine disc, WanFang data, China National Knowledge Infrastructure, Embase, PubMed, CINAHL, Web of Science, and Cochrane Library. The search timeframe was from the establishment of the databases to September 30, 2023, limited to English and Chinese languages. Two researchers independently screened the literature and extracted data, and the PROBAST tool was used to evaluate the risk of bias and applicability of the included studies.Results:A total of 15 studies on VAP risk prediction models were included. The area under the receiver operating characteristic curve for the 15 models ranged from 0.722 to 0.982. The most frequently involved predictors were age, duration of mechanical ventilation, ICU length of stay, and comorbid chronic obstructive pulmonary disease. The overall adaptability was good, but the risk of bias was high. The main sources of bias included insufficient sample size, inappropriate data sources, lack of model performance evaluation, and inadequate attention to missing data.Conclusions:The risk of bias in studies on VAP risk prediction models is high, indicating that the field is still developing. Future research should focus on the effectiveness of different risk assessment methods to construct models with low bias, excellent predictive performance, and suitability for clinical practice in China.

Objective To develop and test the reliability and validity of the Intrinsic Capacity Assessment Scale for the Older People,so as to provide an effective tool for the assessment of the intrinsic capacity of the aged.Methods Based on the International Classification of Functioning,Disability and Health(ICF)as the theoretical framework,the initial version of The Intrinsic Capacity Assessment Scale for the Older People was developed through literature analysis,Delphi expert consultation and pre-survey.From July to September 2023,650 old people were selected by convenience sampling method to conduct a survey,and 20 old people were surveyed after 2 weeks again to test the reliability and validity of the scale.Results The effective questionnaire recovery rates of the 2 rounds of expert correspondence were 92.3％and 91.7％;the expert authority coefficients were 0.83 and 0.86;the mean importance scores of items were 2.04-3.79 and 3.50-3.82,and the full score ratios were 4.2％-83.3％and 54.6％-86.4％,respectively.The coefficients of variation were 0.11-0.42 and 0.11-0.23,respectively.A total of 5 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 68.327％.The results of confirmatory factor analysis showed that the fit indexes were x2/df=1.908,RMSEA=0.054,CFI=0.931,IFI=0.932,TLI=0.922,indicating a good fit.The Cronbach's α coefficient of the scale was 0.944;the split half reliability was 0.806;the retest reliability was 0.933.The content validity index of item level was 0.82-1.00,and the content validity index of scale level was 0.91.The Intrinsic Capacity Assessment Scale for the Older People included 35 items in 5 dimensions:movement,vitality,sensation,cognition and psychology.Conclusion The Intrinsic Capacity Assessment Scale for the Older People has good reliability and validity,and it can be used as a reliable tool to evaluate the intrinsic capacity level of the aged.

Objective:To determine the median effective dose (ED 50) of remimazolam for preoperative sedation in pediatric patients of different ages. Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification I or Ⅱ pediatric patients, aged 1-6 yr, scheduled for elective surgery in our hospital from July to December 2023, in whom the preoperative anxiety was still not relieved after non-drug intervention (preoperative separation anxiety score [PSAS]≥3), were selected. According to the age, the children were divided into 1-<2 yr group, 2-<3 yr group, 3-<4 yr group, 4-<5 yr group and 5-6 yr group. A child's PSAS score = 1 at the time of separation from parents was classified as satisfactory sedation, and a PSAS score ≥ 2 was classified as unsatisfactory sedation. The initial dose of remimazolam in each group was 0.3 mg/kg, dose ratio 1.15. If the child was satisfactorily sedated, the next patient received a lower dose of remimazolam, or conversely if the child was not satisfactorily sedated, a higher dose was given in the next patient. The test was ended when 7 alternating waveforms appeared. The Dixon-Massey method was used to calculate the ED 50 and 95% confidence interval. Results:In 1-<2 yr group, 2-<3 yr group, 3-<4 yr group, 4-<5 yr group and 5-6 yr group, a total of 120 children were included in this study, with 26, 23, 21, 27 and 23 cases, respectively, and the ED 50 (95% confidence interval) of remimazolam for preoperative sedation was 0.152 (0.126-0.178), 0.159 (0.135-0.183), 0.171 (0.147-0.196), 0.150 (0.126-0.174), and 0.146 (0.121-0.170) mg/kg, respectively. There was no significant difference between the groups ( P>0.05). Conclusions:The ED 50 of remimazolam for preoperative sedation is 0.152, 0.159, 0.171, 0.150 and 0.146 mg/kg for every 1 yr in children aged 1-6 yr, and the age factor does not affect the preoperative sedative effect of remimazolam in children of this age group.

This article presented the maternal and infant outcomes of glycogen storage disease type Ⅲa (GSDⅢa) in a woman with full-term pregnancy. The woman exhibited symptoms of hypoglycemia when she was three months old, which were alleviated with intravenous glucose infusion. At the age of 19, during surgical treatment for scoliosis, she was found with liver cirrhosis, splenomegaly, and thrombocytopenia. Glycogen debranching enzyme deficiency was detected through liver biopsies, leading to the clinical diagnosis of GSDⅢ (unspecified genotype). The patient was admitted after conceiption due to "irregular lower abdominal pain for 1 day" at 34 weeks and 3 days. Through multidisciplinary management in the late pregnancy, which included medication adjustments, dietary instruction, and platelet transfusions both at half an hour before and during the operation, the patient underwent a cesarean section at 37 +1 weeks of gestation and delivered a healthy boy with normal Apgar scores at 1, 5, and 10 min. The mother followed a high-protein diet postpartum and the newborn experienced hypoglycemia after birth. Intravenous glucose was supplied to the infant, restabilizing his blood glucose. Maternal and neonatal blood glucose both remained stable. Postpartum whole-exome sequencing identified compound heterozygous variants in the mother, which were in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*) and at chr1:100345603 with gene variant information of NM_000642.2:c.1735+1G>T, confirming the diagnosis of GSDⅢa. The newborn carried a heterozygous variant in the AGL gene at chr1:100379102-100379103 with gene variant information of NM_000642.2:c.3971_3972delAT(p.Tyr1324*). Postpartum follow-ups showed stable blood glucose levels for the mother and normal growth and development for the newborn.

Objective:To preliminarily investigate the applicability of a poliovirus pseudovirus-based neutralization assay in evaluating the immunogenicity of recombinant poliovirus vaccines and their in vivo potency in rats. Methods:Serum samples from rats immunized with recombinant poliovirus vaccines were tested using both the pseudovirus neutralization assay and the live-virus neutralization assay with Sabin strain. The consistency and correlation of the two methods were analyzed using the Kappa test and Spearman′s rank correlation.Results:For the neutralizing antibodies against typeⅠ, Ⅱ, and Ⅲ polioviruses, the Kappa values for consistency analysis of the two methods were 0.914, 1.000, and 0.751, respectively ( P<0.001), and the correlation coefficients ( R values) were 0.833, 0.927, and 0.859, respectively ( P<0.001). Conclusions:The test results of the two methods are consistent and show a good correlation, indicating that the pseudovirus neutralization assay can be applied to evaluating the immunogenicity of poliovirus vaccines and also can be used in rat potency tests.

Objective To address the issue of missing entity relationship information in the knowledge graph of TCM ancient books;To propose a knowledge reasoning method based on deep reinforcement learning;To improve the completeness of the knowledge graph.Methods Based on the benchmark dataset in the field of knowledge graph and the dataset of TCM ancient books,a deep reinforcement learning inference method was adopted.Combined with knowledge one-step completion and multi hop path search,Python language was used in conjunction with the Neo4j graph database to achieve path to path inference.Results In the knowledge reasoning task dataset,compared with the baseline model,this reasoning method improved the MAP index by about 53.79%.When applied to the knowledge graph of TCM ancient books,its evaluation index reached the highest of 0.776.Conclusion The knowledge reasoning method based on deep reinforcement learning has significant advantages in improving the completeness of the knowledge graph of TCM ancient books,and this method can effectively fill the information gap in the graph of TCM ancient books.

Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.

ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma（DBR） processed with Phaseoli Radiati Semen（PRS） juice， and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group， DBR group， water roasted DBR group（hereinafter referred to as water group）， PRS juice-roasted DBR group 1（DBR-PRS 10∶1， stuffy moistening for 40 min， stir-fried at 130 ℃ for 18 min， hereinafter referred to as group 1）， PRS juice-roasted DBR group 2（DBR-PRS 10∶1， stuffy moistening for 80 min， stir-fried at 100 ℃ for 14 min， hereinafter referred to as group 2）， PRS juice-roasted DBR group 3（DBR-PRS=20∶3， stuffy moistening for 40 min， stir-fried at 160 ℃ for 14 min， hereinafter referred to as group 3）. The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg^-1·d^-1， while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose， once a day for 14 consecutive days. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels in serum， as well as malondialdehyde（MDA）， ferrous ions（Fe²⁺）， reduced glutathione（GSH） and superoxide dismutase（SOD） levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1（FTH1） and glutathione peroxidase 4（GPX4）. ResultHE staining results showed that the liver tissue structure of the blank group was clear， the morphology of hepatocytes was normal， the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar， with obvious pathological damages， and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group， the levels of ALT， AST， MDA and Fe²⁺ in mice from the DBR group were significantly increased（P<0.01）， while GSH and SOD levels were significantly reduced（P<0.01）， and the protein expression levels of FTH1 and GPX4 were significantly decreased（P<0.01）. Compared with the DBR group， the ALT， AST，MDA and Fe²⁺ levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased（P<0.01）. Compared with the water group， the AST and MDA levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the SOD level significantly increased（P<0.05， P<0.01）， the FTH1 protein expression significantly increased（P<0.01）， and the serum ALT level of mice in the group 2-3 significantly reduce（P<0.01）， Fe²⁺ level significantly reduced（P<0.01）， GSH level significantly increased（P<0.05， P<0.01）， and GPX4 protein expression significantly increased（P<0.05， P<0.01）. Among the group 1-3， the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR， and the mechanism may be related to the inhibition of ferroptosis in the liver.