ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

In recent years, significant progress has been made in pharmacological research on the treatment of ischemic stroke with monomeric components of traditional Chinese medicine, among which flavonoids have shown good neuroprotective effects. This article reviews the regulatory role of flavonoids in the signaling pathway of ischemic brain injury.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. METHODS: A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56). RESULTS: The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c.289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. CONCLUSION The homozygous c.289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.
Humans ; Male ; Spastic Paraplegia, Hereditary/genetics* ; Child, Preschool ; Female ; Exome Sequencing ; Child ; Infant ; Adaptor Protein Complex 4/genetics* ; Phenotype ; Mutation

The rapid development of artificial intelligence （AI） technology provides new opportunities for the modernisation of traditional Chinese medicine （TCM） diagnosis. By analysing the foundation， research progress and difficulties of the combination of AI and TCM diagnosis， it is concluded that AI has made remarkable development in intelligence-driven modernization of TCM tongue diagnosis， pulse diagnosis， listening and smelling diagnosis and text processing， and there are useful explorations in the field of constructing data-driven TCM diagnostic model and multidisciplinary integration of TCM diagnostic models. However， the current integration of AI technology in TCM diagnosis still faces many challenges， such as the scarcity and uneven quality of clinical data， the limited ability of AI algorithms to express TCM thinking model of syndrome differentiation and empirical knowledge， and the possible existence of ethical and privacy issues. By systematically sorting out the current research status and development direction of AI-empowered TCM diagnostics， it is proposed to promote the application of AI technology in TCM diagnostics in four aspects， namely， strengthening the construction of TCM big data and talent cultivation， encouraging cross-disciplinary cooperation， improving the legal and ethical framework， and promoting the popularity of the technology in primary care， so as to enhance the modernisation of TCM diagnostics.

Acute ischemic stroke (AIS) is the main subtype of stroke, caused by impaired blood supply to the brain. Timely restoration of blood perfusion is crucial for improving prognosis. A growing number of studies have shown that inflammatory markers and blood biomarkers, such as C-reactive protein (CRP), lymphocyte-to-monocyte ratio (LMR), monocyte-to-high-density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII), have predictive effects on the prognosis of intravenous thrombolysis (IVT) in ischemic stroke. This article summarizes the research progress of inflammatory markers related to the prognosis of IVT in AIS, aiming to early identify adverse prognosis (such as early neurological deterioration, END) in patients undergoing IVT, conduct risk stratification for patients, formulate precise and effective treatment plans, and reduce related complications.

Objective:To explore the clinical phenotype and genetic characteristics of a child with hereditary Spastic paraplegia type 52 (SPG52) due to variant of AP4S1 gene. Methods:A child diagnosed with SPG52 at the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University in May 2010 was selected as the study subject. Whole-exome sequencing (WES) was carried out for the child and his parents. Candidate variants were confirmed by Sanger sequencing. Pathogenicity of the candidate variant was interpreted according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). The study protocol was approved by the Ethics Committee of the Hospital (Ethics No.: PJ2024-04-56).Results:The child had presented with global developmental delay from infancy, and featured progressive lower limb spasticity, contractures, talipes equinovarus, and muscle weakness, but with no significant facial dysmorphism. His first febrile seizure occurred before one year of age, followed by several afebrile seizures. The seizures had remitted after 3 to 4 years of antiepileptic therapy, and electroencephalography was normal. However, he had severe intellectual disability, and MRI revealed reduced white matter. WES identified a homozygous AP4S1 c. 289C>T (p.Arg97*) variant in the child, for which both of his parents were heterozygous carriers. The variant was rated as pathogenic based on the ACMG guidelines. Literature review has identified 8 publications on SPG52, involving 18 patients from 12 pedigrees. Combined with our case, 14 had carried homozygous variants of the AP4S1 gene, 3 had compound heterozygous variants, and 2 had heterozygous variants, involving 12 distinct variant sites. The cohort included 7 males and 12 females. All patients exhibited progressive lower limb spasticity and weakness as the primary feature, with certain loss of independent ambulation. Most patients had intellectual disability, some had distinctive facial features, though febrile seizures or epilepsy were common. Electroencephalography often showed increased slow-wave activity. Brain MRI frequently demonstrated ventriculomegaly, a thin corpus callosum, and reduced white matter. Conclusion:The homozygous c. 289C>T (p.Arg97*) variant of the AP4S1 gene probably underlay the pathogenesis of SPG52 in this child. Above discovery has expanded the mutational spectrum of AP4S1 and provided valuable insights for the genetic diagnosis, counseling, and clinical management of SPG52.

Acute ischemic stroke (AIS) is the main subtype of stroke, caused by impaired blood supply to the brain. Timely restoration of blood perfusion is crucial for improving prognosis. A growing number of studies have shown that inflammatory markers and blood biomarkers, such as C-reactive protein (CRP), lymphocyte-to-monocyte ratio (LMR), monocyte-to-high-density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII), have predictive effects on the prognosis of intravenous thrombolysis (IVT) in ischemic stroke. This article summarizes the research progress of inflammatory markers related to the prognosis of IVT in AIS, aiming to early identify adverse prognosis (such as early neurological deterioration, END) in patients undergoing IVT, conduct risk stratification for patients, formulate precise and effective treatment plans, and reduce related complications.

Objective:To explore the changes in serum indoleamine 2, 3-dioxygenase (IDO) and kynurenic acid (KYNA) levels in preterm infants diagnosed with bronchopulmonary dysplasia (BPD).Methods:A nested case-control study was conducted. The inclusion criteria covered premature infants with less than 32 weeks of gestational age within 24 h post-birth, from December 1, 2021, to December 31, 2022, at Children's Hospital of Soochow University. Those diagnosed with BPD were allocated to the BPD group ( n=35). Non-BPD preterm infants matching the BPD cases in terms of gestational age (within one week difference) and birth weight (within a 150 g difference) were selected in a 1∶1 ratio for the control group ( n=35). Serum levels of IDO and KYNA were measured on days 1, 7, 14, and 28 postnatally. Differences in serum IDO and KYNA levels were analyzed between the BPD and control groups and among infants with mild BPD versus moderate-to-severe BPD. The association between serum IDO and KYNA levels with the severity of BPD was also assessed. Statistical analysis was conducted using independent samples t-tests and Spearman's correlation analysis. Results:Elevated levels of serum IDO on days 7, 14, and 28 postnatally [(60.68±9.37) vs. (50.66±10.46), (57.81±11.07) vs. (44.45±8.20), and (50.62±10.77) vs. (41.31±7.74) pg/ml; t=4.21, 5.73, and 4.15, respectively] as well as increased serum KYNA levels on days 14 and 28 [(439.31±41.22) vs. (368.99±68.79), (376.97±45.74) vs. (325.50±60.07) μmol/L; t=5.18 and 4.03, respectively] were observed in the BPD group compared to the control group, with all differences being statistically significant (all P<0.05). Furthermore, positive correlations were observed between serum IDO levels and BPD severity on the 7th, 14th, and 28th days ( r=0.546, 0.495, and 0.502, all P<0.05), as well as between serum KYNA levels and BPD severity on the 14th and 28th days ( r=0.536 and 0.458, both P<0.05). Conclusion:Elevated serum levels of IDO and KYNA in infants with BPD suggest these metabolites may play a role in the pathogenesis and progression of BPD.

[Objective] To explore the clinical significance of the IgG1 and IgG3 subtypes of red blood cell unexpected antibodies. [Methods] The IgG1 and IgG3 typing tests were performed on the IgG type alloantibodies of Rh, Duffy and Kidd blood group systems detected in our hospital. Additionally, IgG1 and IgG3 titers were measured and monocyte monolayer assay was performed on 12 cases of anti-E to analyze the characteristics of different IgG subtypes of anti-E. [Results] Among the 115 cases of unexpected IgG antibodies, 81 cases of monospecific antibodies were predominantly IgG1 (58.02%, 47/81); 17 cases of mixed antibodies were predominantly IgG1+IgG3 (47.06%, 16/34). In monocyte monolayer assays, the phagocytic rate and antibody titer of IgG1 and IgG3 antibodies were positively correlated, while in IgG1+IgG3 complex antibodies, it was mainly associated with IgG3, with higher antibody titers correlating with higher phagocytic rates. When the anti-E titers were 32 for all, the IgG1+IgG3 complex had the highest phagocytosis rate, followed by IgG3 alone, and IgG1 alone had the lowest phagocytic rate. [Conclusion] Monospecific antibodies among unexpected antibodies are primarily IgG1, while mixed antibodies are mainly IgG1+IgG3. The results of MMA indicate that the immune response caused by the IgG1+IgG3 complex is more severe. Therefore, when antibodies like anti-E coexist with other antibodies, even if the titer is low, the immune response may still be severe, which should be taken seriously in clinical practice.