Pediatric acute liver failure (PALF) is a rare and critical clinical syndrome with a poor prognosis. Its etiology is complex, with a significant proportion of cases having remained classified as indeterminate or cryptogenic PALF. With the application of high-throughput sequencing technologies, a spectrum of disorders caused by specific genetic metabolic defects and characterized by stress-sensitive Recurrent acute liver failure (RALF) has been gradually unveiled, collectively termed Infantile liver failure syndrome (ILFS). Although the molecular mechanisms underlying the subtypes ILFS1, ILFS2, and ILFS3 differ by involving aminoacyl-tRNA synthetase defects, vesicular transport disorders, and autophagy abnormalities, respectively, they share a common clinical phenotype of RALF triggered by fever or infection. This article has systematically reviewed the clinical phenotypic spectrum, molecular genetic characteristics, differential diagnosis strategies, and therapeutic advances of the three ILFS subtypes, with the goal of improving early clinical recognition and precise intervention, and providing an important reference for evaluating the prognosis of different subtypes.
Humans ; Liver Failure, Acute/therapy* ; Infant ; Diagnosis, Differential

ObjectiveTo investigate the mechanism of Hei Xiaoyaosan （HXS） in ameliorating cognitive impairment in the rat model of Alzheimer's disease （AD） by regulating the adenosine 5'-monophosphate-activated protein kinase （AMPK）/sterol regulatory element-binding protein 2 （SREBP2）/proprotein convertase subtilisin/kexin type 9 （PCSK9）/low-density lipoprotein receptor-related protein 1 （LRP-1） signaling pathway to clear amyloid-β （Aβ） from the peripheral circulation. MethodsNinety 8-week-old specific pathogen-free （SPF）-grade male Sprague-Dawley （SD） rats were acclimatized for 1 week. After acclimatization， 10 rats were randomly selected as the blank control group， and the remaining 80 rats were prepared for surgical modeling. Among the 80 rats for modeling， 70 were anesthetized and injected with 1 μL of amyloid-β_1-42 （Aβ_1-42） solution into the bilateral hippocampal CA1 region for the modeling of AD， and the remaining 10 were assigned to the sham operation group， which received an injection of 1 μL normal saline at the same anatomical site. The successfully modeled rats were randomly assigned into 6 groups （n=10 per group）： a model group， a donepezil hydrochloride group， an acadesine （AICAR， an AMPK agonist） group， and high-， medium-， and low-dose HXS groups. After 42 consecutive days of administration intervention， the Morris water maze test and T-maze test were performed to evaluate the learning and memory abilities of rats. Fluoro-Jade B （FJB） staining was conducted to observe pathological changes of neurons in the rat hippocampus， and thioflavin S staining to quantify the area of Aβ deposition in the hippocampal region. Immunofluorescence double staining （IF-DS） was performed to detect the expression of LRP-1 and Aβ signals in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of Aβ_1-42 and soluble LRP-1 （sLRP-1） in the serum. Western blot was performed to determine the protein levels of AMPK， phosphorylated AMPK （p-AMPK）， SREBP2， PCSK9， and LRP-1 in the liver tissue. Real time polymerase chain reaction（Real-time PCR） was adopted to assess the mRNA levels of AMPK， SREBP2， PCSK9， and LRP-1 in the liver tissue. ResultsCompared with the blank control group， the model group showed increased total swimming distance on day 6 and path length in the target quadrant on day 7 （P<0.01）， a decreased correct alternation rate in the T-maze test （P<0.01）， disarrangement of hippocampal neurons， increased FJB-positive cells （P<0.01）， enlarged area of Aβ deposition （P<0.01）. reduced LRP-1 fluorescence signals and enhanced Aβ fluorescence signals in the liver tissue （P<0.01）， elevated serum level of Aβ_1-42， declined serum level of sLRP-1 （P<0.01）， downregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and upregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）. Compared with the model group， the high-dose HXS group， donepezil hydrochloride group， and AICAR group exhibited reduced total swimming distance and target quadrant path length （P<0.05， P<0.01）， an increased correct alternation rate in the T-maze test （P<0.05）， decreased FJB-positive cells （P<0.01）， reduced Aβ deposition （P<0.01） in the hippocampal tissue， enhanced LRP-1 signals and weakened Aβ signals in the liver tissue （P<0.01）， a declined serum level of Aβ_1-42 and an elevated serum level of sLRP-1 （P<0.01）， upregulated protein levels of p-AMPK and LRP-1 as well as mRNA levels of AMPK and LRP-1， and downregulated protein and mRNA levels of SREBP2 and PCSK9 in the liver tissue （P<0.01）. ConclusionHei Xiaoyaosan can regulate the AMPK/SREBP2/PCSK9/LRP-1 signaling pathway to enhance the clearance of peripheral Aβ by the liver tissue and reduce Aβ deposition in the brain， thereby improving the learning and memory abilities of AD rats.

ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in regulating asparaginyl endopeptidase （AEP） to inhibit tau protein （tau） phosphorylation， amyloid-beta protein （Aβ） deposition， and neuroinflammation in the prevention and treatment of Alzheimer's disease （AD）. MethodsNinety SPF-grade SD male rats of 8 weeks old were selected and randomly grouped as follows： 10 rats in the blank group， 10 rats in the sham group （bilateral hippocampus injected with 1 μL normal saline）， and 70 rats in the modeling group （bilateral hippocampus injected with 1 μL Aβ_1-42 solution for the modeling of AD）. Fifty successfully modeled rats were selected and randomly assigned into the model， donepezil hydrochloride （positive control， 0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups. Rats were administrated with corresponding agents by gavage once a day for 42 days. Morris water maze and Y maze tests were carried out to assess the cognitive abilities of rats. Hematoxylin-eosin （HE） staining was employed to observe morphological changes in hippocampal neurons， and immunohistochemistry （IHC） was employed to assess phosphorylation （p）-tau and Aβ expression in the hippocampal tissue of rats. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of interleukin-1 beta （IL-1β）， interleukin-18 （IL-18）， and Aβ_1-42 in the hippocampal tissue. Western blot was employed to determine the protein levels of AEP， tau， phosphorylated tau （p-tau）， α-Syn （α-Syn）， phosphorylated α-Syn （p-α-Syn）， Toll-like receptor 2 （TLR2）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3）. Real time polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of AEP， tau， α-Syn， TLR2， and NLRP3. ResultsCompared with the blank group， the model group showed prolonged escape latency， a decreased percentage of time spent in the platform quadrant， and a decreased alternation rate （P<0.01）， a reduced number， shrinkage， and increased vacuoles of hippocampal neurons， increased expression of p-tau and Aβ in the hippocampus （P<0.01）， elevated levels of IL-1β， IL-18， and Aβ_1-42， up-regulated protein and mRNA levels of AEP， tau， α-Syn， TLR2， and NLRP3， and up-regulated protein levels of p-tau and p-α-Syn （P<0.01）. Compared with the model group， the positive control group and the high-dose Hei Xiaoyaosan group exhibited shortened escape latency （P<0.01）， an increased percentage of retention time in the target quadrant， an increased alternation response rate （P<0.05， P<0.01）， alleviated neuronal shrinkage， regular morphology and arrangement of neurons in the hippocampal tissue， lowered levels of p-tau and Aβ in the hippocampal tissue （P<0.05， P<0.01）， declined levels of IL-1β， IL-18， and Aβ_1-42， downregulated mRNA and protein levels of AEP， tau， α-Syn， TLR2， and NLRP3， and downregulated protein levels of p-tau and p-α-Syn （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can protect hippocampal neurons and ameliorate cognitive impairment in the rat model of AD. Specifically， it may inhibit AEP to regulate tau phosphorylation， Aβ deposition， and neuroinflammation.

ObjectiveTo investigate the effect and mechanism of Hei Xiaoyaosan in preventing and treating Alzheimer's disease （AD） by activating autophagy through regulating the adenosine monophosphate-activated protein kinase （AMPK）/UNC-51 like autophagy activating kinase 1 （ULK1） signaling pathway. MethodsNinety 8-week-old male SPF-grade SD rats were selected and randomized into two groups： a blank control group （n=10） and a modeling group （n=80）. From the modeling group， 10 rats were randomly assigned as a sham group （bilateral hippocampal injection of 1 μL normal saline）， while the remaining 70 rats were injected with 1 μL Aβ_1-42 solution bilaterally into the hippocampus to replicate the AD model. The Morris water maze test was conducted to screen the successfully modeled rats， which were then randomly allocated to the model， donepezil hydrochloride， 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside （AICAR， an AMPK agonist）， and high-， medium-， and low-dose Hei Xiaoyaosan groups， with 10 rats per group. After 42 days of drug intervention， the Morris water maze and open field tests were conducted to assess learning and memory abilities and motor function. Pathological changes in the hippocampal tissue were observed by Nissl staining， and autophagy-related pathological damage was examined via transmission electron microscopy （TEM）. The expression of LC3 in the hippocampus was observed by immunofluorescence staining. The protein levels of AMPK， phosphorylate （p）-AMPK， ULK1， p-ULK1， p62， and autophagy related 7 （Atg7） were determined by Western blot， while the mRNA levels of AMPK and ULK1 were measured by Real-time polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank control group， the model group showed increased escape latency （P<0.01） and decreased platform crossings （P<0.01） on day 6 in the water maze test， reduced total distance traveled and average speed in the open field test （P<0.01）， disarranged neurons with Nissl body loss and evident autophagic damage， weakened LC3 fluorescence signal （P<0.01）， downregulated protein levels of p-AMPK， p-ULK1， and Atg7 and mRNA levels of AMPK and ULK1 in the hippocampus （P<0.01）， and upregulated protein level of p62 （P<0.01）. Compared with the model group， the positive drug group， high-dose Hei Xiaoyaosan group， and AICAR group showed decreased escape latency （P<0.05， P<0.01） and increased platform crossings （P<0.01） on day 6， and increased total distance traveled and average speed in the open field test （P<0.05）. The positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group showed alleviated cellular structural damage， regular neuronal arrangement， increased Nissl bodies， and orderly distribution of autophagosomes. Furthermore， the LC3 fluorescence intensity was enhanced in the positive drug group， high- and medium-dose Hei Xiaoyaosan groups， and the AICAR group （P<0.01）. The positive drug group， high-dose Hei Xiaoyaosan group， and the AICAR group exhibited upregulated protein and mRNA levels of p-AMPK and p-ULK1 （P<0.05， P<0.01）， upregulated protein level of Atg7 （P<0.05， P<0.01）， and downregulated protein level of p62 （P<0.01）. ConclusionHei Xiaoyaosan can improve learning and memory abilities and alleviate pathological status in the rat model of AD by regulating the AMPK/ULK1 signaling pathway， enhancing cellular autophagy， and repairing damaged nerve cells.

Objective:To detect the expression of sialylated CD15 (CD15s) in the tumor cells of classical Hodgkin lymphoma using a modified immunohistochemical approach.Methods:From 2009 to 2024, 53 cases of classical Hodgkin lymphoma were collected in the Department of Pathology, Peking University Cancer Hospital, in which 21 cases that were CD15-negative or showed only focal weak positivity were selected. Immunohistochemical staining for CD15 was performed on a Leica automated stainer using three different antibody clones (MMA, Carb3, and IHC527). Tissue sections were digested with sialidase at varying concentrations and incubation times, followed by immunohistochemical staining with the MMA clone. Multiplex immunofluorescence was applied for co-staining of CD15 (MMA) and CD30 (JCM182), and analysis was conducted using APTIME and HALO software.Results:There were 30 male patients and 23 female patients, with an age range of 14 to 73 years and a median age of 32(26,46) years. None of the three CD15 antibody clones significantly improved the CD15 positive rate in the 14 completely negative and 7 weakly positive cases, with no notable differences observed among the clones( P>0.05). After sialidase digestion, tissue morphology remained well-preserved. Optimal CD15 staining was achieved with a 1∶1 diluted sialidase incubated at 37 ℃ for one hour. This treatment significantly enhanced the detection rate of CD15 antigen in Hodgkin Reed-Sternberg cells ( P<0.001). Conclusion:Sialidase digestion effectively unveils sialylated CD15 expression in classical Hodgkin lymphoma, markedly improving its detection in HRS cells.

Objective:To detect the expression of sialylated CD15 (CD15s) in the tumor cells of classical Hodgkin lymphoma using a modified immunohistochemical approach.Methods:From 2009 to 2024, 53 cases of classical Hodgkin lymphoma were collected in the Department of Pathology, Peking University Cancer Hospital, in which 21 cases that were CD15-negative or showed only focal weak positivity were selected. Immunohistochemical staining for CD15 was performed on a Leica automated stainer using three different antibody clones (MMA, Carb3, and IHC527). Tissue sections were digested with sialidase at varying concentrations and incubation times, followed by immunohistochemical staining with the MMA clone. Multiplex immunofluorescence was applied for co-staining of CD15 (MMA) and CD30 (JCM182), and analysis was conducted using APTIME and HALO software.Results:There were 30 male patients and 23 female patients, with an age range of 14 to 73 years and a median age of 32(26,46) years. None of the three CD15 antibody clones significantly improved the CD15 positive rate in the 14 completely negative and 7 weakly positive cases, with no notable differences observed among the clones( P>0.05). After sialidase digestion, tissue morphology remained well-preserved. Optimal CD15 staining was achieved with a 1∶1 diluted sialidase incubated at 37 ℃ for one hour. This treatment significantly enhanced the detection rate of CD15 antigen in Hodgkin Reed-Sternberg cells ( P<0.001). Conclusion:Sialidase digestion effectively unveils sialylated CD15 expression in classical Hodgkin lymphoma, markedly improving its detection in HRS cells.

Objective:To investigate the application value of cervical vascular ultrasound(CVUS)combined with transcranial Doppler ultrasound(TCD)in the diagnosis of carotid artery stenosis and collateral circulation in patients with ischemic cerebrovascular disease(ICVD).Methods:In this study,86 patients with ICVD admitted to the Cardio-Cerebrovascular Disease Specialist Hospital of Qinghai Province from January 2021 to January 2023 were selected.All patients underwent CVUS,TCD and digital subtraction cranial angiography(DSA)examination,and the diagnosis results of DSA were taken as the gold standard.To observe and compare the diagnostic efficacy of CVUS and TCD alone and combined CVUS and TCD for carotid artery stenosis and collateral circulation in ICVD patients.Results:Among the 86 patients with ICVD,a total of 597 vascular stenoses were detected by DSA examination,424 vascular stenoses were detected by CVUS,388 vascular stenoses were detected by TCD,and 586 vascular stenoses were detected by CVUS combined with TCD.The diagnostic coincidence rates of CVUS and TCD alone detection were 71.02%(424/597)and 64.99%(388/597),respectively,and the diagnostic coincidence rate of the combined detection of the two methods was 98.16%(586/597).The comparison showed that there was no statistically significant difference in the diagnostic coincidence rate of the degree of vascular stenosis between CVUS combined with TCD detection and DSA(P>0.05).Among the 86 patients with ICVD,collateral circulation formation was detected in 69 cases by DSA,in 55 cases by CVUS,in 51 cases by TCD,and in a total of 67 cases by CVUS combined with TCD.There was no significant difference in the detection rate between the combined detection of CVUS and TCD and that of DSA(P>0.05).Through analysis,it was concluded that the diagnostic sensitivity and accuracy of CVUS combined with TCD detection were both higher than those of CVUS and TCD single detection,and the difference was statistically significant(x2=10.180 and 12.204,P<0.05)14.969 and 18.124,P<0.05).The accuracy rate of the combined detection of CVUS and TCD was 96.51%,the sensitivity was 97.10%,and the specificity was 94.12%,which was highly consistent compared with DSA(Kappa value=0.896).Conclusion:CVUS combined with TCD detection has high clinical application value in the diagnosis of carotid artery stenosis and collateral circulation in ICVD patients.The combined detection of the two methods can further improve the diagnostic sensitivity,and the diagnostic accuracy is close to the gold standard,which can provide a reliable reference for clinical rational treatment and improvement of prognosis.

Objective:To develop the Home-based Self-management Efficacy Questionnaire for Stable Chronic Obstructive Pulmonary Disease (COPD) Patients and test its reliability and validity.Methods:Guided by the individual and family self-management theory and self-management efficacy theory, a preliminary questionnaire was developed through literature analysis, semi-structured interviews, and expert inquiries. From September to November 2022, convenience sampling was used to select stable COPD patients of the Respiratory Department of Tongji University Shanghai Pulmonary Hospital as participants for investigation for project analysis and exploratory factor analysis of the questionnaire. From December 2022 to January 2023, a survey was conducted on stable COPD patients who visited the Respiratory Department of Tongji University Shanghai Pulmonary Hospital and Yancheng Third People's Hospital to conduct confirmatory factor analysis and reliability testing on the questionnaire.Results:A total of 220 and 290 questionnaires were distributed respectively, and 214 and 280 valid questionnaires were collected, with effective response rates of 97.27% (214/220) and 96.55% (280/290), respectively. The Home-based Self-management Efficacy Questionnaire for COPD Patients included six dimensions and 28 items. The questionnaire's total Cronbach's α coefficient was 0.910, and the half-confidence coefficient was 0.806. The content validity index at the questionnaire level was 0.928, and the content validity index at the item level was 0.800 to 1.000. The exploratory factor analysis showed that a total of six common factors were extracted, with a cumulative variance contribution rate of 63.943%. Confirmatory factor analysis showed that the model fitted well and the questionnaire factor structure was stable.Conclusions:The the Home-based Self-management Efficacy Questionnaire for Stable COPD has been developed with good reliability and validity, providing a reference for medical and nursing staff to evaluate the home self-management efficacy of stable COPD patients.

Objective:To investigate the application value of cervical vascular ultrasound(CVUS)combined with transcranial Doppler ultrasound(TCD)in the diagnosis of carotid artery stenosis and collateral circulation in patients with ischemic cerebrovascular disease(ICVD).Methods:In this study,86 patients with ICVD admitted to the Cardio-Cerebrovascular Disease Specialist Hospital of Qinghai Province from January 2021 to January 2023 were selected.All patients underwent CVUS,TCD and digital subtraction cranial angiography(DSA)examination,and the diagnosis results of DSA were taken as the gold standard.To observe and compare the diagnostic efficacy of CVUS and TCD alone and combined CVUS and TCD for carotid artery stenosis and collateral circulation in ICVD patients.Results:Among the 86 patients with ICVD,a total of 597 vascular stenoses were detected by DSA examination,424 vascular stenoses were detected by CVUS,388 vascular stenoses were detected by TCD,and 586 vascular stenoses were detected by CVUS combined with TCD.The diagnostic coincidence rates of CVUS and TCD alone detection were 71.02%(424/597)and 64.99%(388/597),respectively,and the diagnostic coincidence rate of the combined detection of the two methods was 98.16%(586/597).The comparison showed that there was no statistically significant difference in the diagnostic coincidence rate of the degree of vascular stenosis between CVUS combined with TCD detection and DSA(P>0.05).Among the 86 patients with ICVD,collateral circulation formation was detected in 69 cases by DSA,in 55 cases by CVUS,in 51 cases by TCD,and in a total of 67 cases by CVUS combined with TCD.There was no significant difference in the detection rate between the combined detection of CVUS and TCD and that of DSA(P>0.05).Through analysis,it was concluded that the diagnostic sensitivity and accuracy of CVUS combined with TCD detection were both higher than those of CVUS and TCD single detection,and the difference was statistically significant(x2=10.180 and 12.204,P<0.05)14.969 and 18.124,P<0.05).The accuracy rate of the combined detection of CVUS and TCD was 96.51%,the sensitivity was 97.10%,and the specificity was 94.12%,which was highly consistent compared with DSA(Kappa value=0.896).Conclusion:CVUS combined with TCD detection has high clinical application value in the diagnosis of carotid artery stenosis and collateral circulation in ICVD patients.The combined detection of the two methods can further improve the diagnostic sensitivity,and the diagnostic accuracy is close to the gold standard,which can provide a reliable reference for clinical rational treatment and improvement of prognosis.

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*