ObjectiveTo investigate the distribution and characteristics of traditional Chinese medicine （TCM） syndromes in patients with colorectal cancer and metabolic dysfunction-associated fatty liver disease （CRC-MAFLD）， to explore the correlation between influencing factors and syndrome distribution， and to provide a reference for clinical syndrome differentiation. MethodsA total of 319 patients who were admitted to Shanxi Provincial Institute of Traditional Chinese Medicine and The Affiliated Hospital of Shanxi University of Chinese Medicine from January 2021 to December 2025 and were diagnosed with CRC-MAFLD based on pathology and radiological examination were enrolled as subjects， and TCM syndrome differentiation was performed for all subjects. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between multiple groups. The indicators with statistical significance in the univariate analysis were incorporated into the unordered multinomial Logistic regression model， and the syndrome of liver depression and spleen deficiency was set as the reference group to identify the independent influencing factors for each TCM syndrome. ResultsThe main clinical symptoms of CRC-MAFLD included fatigue （78.06%）， abdominal distension （64.26%）， poor appetite （61.13%）， loose stool （57.05%）， and costal pain （52.04%）. The syndrome of liver depression and spleen deficiency showed the highest distribution frequency， followed by intermingled phlegm and blood stasis， internal retention of dampness turbidity， damp-heat accumulation， deficiency of liver and kidney， and deficiency of spleen and kidney. Comparison between groups with different TCM syndromes showed significant differences in the distribution of body mass index （χ²=42.216， P<0.001）， the clinical stage of colorectal cancer （χ²=11.666， P=0.040）， liver metastasis （χ²=19.279， P=0.002）， degree of hepatic steatosis （χ²=71.085， P<0.001）， diabetes （χ²=12.486， P=0.029）， chemotherapy （χ²=21.920， P<0.001）， fasting plasma glucose （FPG） （F=10.367， P<0.001）， glycosylated hemoglobin （HbA1c） （F=3.696， P=0.003）， albumin （Alb） （F=3.302， P=0.006）， alkaline phosphatase （ALP） （H=34.350， P<0.001）， gamma-glutamyl transferase （GGT） （H=41.679， P<0.001）， and triglyceride （TG） （H=28.826， P<0.001）. An unordered multinomial Logistic regression model was constructed with the syndrome of liver depression and spleen deficiency as the reference， and the results showed that overweight/obesity was a common independent risk factor for intermingled phlegm and blood stasis （odds ratio ［OR］=4.468， P=0.002）， internal retention of dampness turbidity （OR=2.944， P=0.024）， and damp-heat accumulation （OR=5.651， P=0.001）； clinical stage Ⅳ was an independent risk factor for deficiency of liver and kidney （OR=6.746， P=0.003） and deficiency of spleen and kidney （OR=10.074， P=0.001）； presence of liver metastasis was an independent risk factor for intermingled phlegm and blood stasis （OR=5.145， P=0.001）； severe fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=5.201， P=0.007） and internal retention of dampness turbidity （OR=7.412， P=0.001）， and moderate fatty liver disease was an independent risk factor for intermingled phlegm and blood stasis （OR=2.643， P=0.045）， internal retention of dampness turbidity （OR=3.182， P=0.029）， and damp-heat accumulation （OR=3.073， P=0.036）； diabetes was an independent risk factor for internal retention of dampness turbidity （OR=5.133， P=0.003） and damp-heat accumulation （OR=3.716， P=0.031）. As for continuous variables， elevated FPG was an independent risk factor for internal retention of dampness turbidity （OR=2.375， P=0.003） and damp-heat accumulation （OR=2.701， P=0.005）； elevated HbA1c was an independent risk factor for intermingled phlegm and blood stasis （OR=2.029， P=0.032） and deficiency of liver and kidney （OR=3.308， P=0.010）； elevated ALP was an independent risk factor for damp-heat accumulation （OR=1.053， P=0.019）； elevated GGT was an independent risk factor for intermingled phlegm and blood stasis （OR=1.029， P=0.026） and damp-heat accumulation （OR=1.030， P=0.047）； elevated TG was an independent risk factor for intermingled phlegm and blood stasis （OR=2.931， P=0.006） and internal retention of dampness turbidity （OR=2.449， P=0.019）； elevated Alb was a protective factor against deficiency of spleen and kidney （OR=0.756， P=0.005）. ConclusionBody mass index， the clinical stage of colorectal cancer， liver metastasis， degree of hepatic steatosis， diabetes， chemotherapy， FPG， HbA1c， Alb， ALP， GGT， and TG are the main influencing factors for TCM syndromes in CRC-MAFLD.

Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Innate immune system serves as the primary defense mechanism against pathogen infections,recognition of structural components of pathogens is referred to as pathogen-associated molecular patterns(PAMPs).Toll-like receptors(TLRs)are a family of transmembrane receptors that can identify PAMPs,which interact with myeloid differentiation factor 88(MyD88)and activate NF-κB dimerization,leading to the release of downstream inflammatory factors and ultimately triggering the adaptive immune system.Conse-quently,TLRs are regarded as adapters that regulate the transition from innate immunity to adaptive immunity.TLR/MyD88/NF-κB signaling pathway plays a crucial role in inflammatory diseases,infectious diseases and tumor immunity.This review article aims to explore the regulatory function of TLR/MyD88/NF-κB signaling pathway in host responses to viral,bacterial,and other microbial in-fections,providing novel insights into the immune response during the process of infection control.

Innate immune system serves as the primary defense mechanism against pathogen infections,recognition of structural components of pathogens is referred to as pathogen-associated molecular patterns(PAMPs).Toll-like receptors(TLRs)are a family of transmembrane receptors that can identify PAMPs,which interact with myeloid differentiation factor 88(MyD88)and activate NF-κB dimerization,leading to the release of downstream inflammatory factors and ultimately triggering the adaptive immune system.Conse-quently,TLRs are regarded as adapters that regulate the transition from innate immunity to adaptive immunity.TLR/MyD88/NF-κB signaling pathway plays a crucial role in inflammatory diseases,infectious diseases and tumor immunity.This review article aims to explore the regulatory function of TLR/MyD88/NF-κB signaling pathway in host responses to viral,bacterial,and other microbial in-fections,providing novel insights into the immune response during the process of infection control.

Objective:To summarize the clinical and genetic features of children with intellectual developmental disorder with seizures and language delay (IDDSELD) due to 12q24.31 deletion and SETD1B locus variants. Methods:The clinical data of a child with 12q24.31 deletion diagnosed in the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in September 2022 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) and copy number variations sequencing (CNV-seq) were used for genetic analysis. The relevant literatures were reviewed to summarize the clinical features of the disease.Results:The proband was a 7 years and 9 month old girl who had clinical features of global developmental delay, epilepsy, hyperactivity, hypertonia, gait disorder, special facial features (high eyebrow arch, big ears, upper lip protrusion), funnel chest, lumbar lordosis. Karyotypic analysis showed 46XX in the proband. CNV-seq showed 12q24.31 (chr12: 121895654-122449092) position had a deletion of about 553.44 kb which contained the SETD1B gene. Trio-WES showed deletion of all exons 1-16 of the SETD1B gene. CNV-seq results of her parents were normal: the SETD1B gene was wild-type. This type has not been reported in China. Four children with IDDSELD caused by 12q24.31 deletion (including the SETD1B gene) were retrieved (totally 5 cases including this case), with male to female ratio of 1∶4, all with de novo mutations, and all with mental retardation, cephalo-facial and skeletal malformations. Three cases had seizures, 2 cases still had developmental backwardness after treatment, and 1 case was seizure controlled. Forty-seven cases of IDDSELD due to point mutation in the SETD1B gene were retrieved: male to female ratio was 31∶16, missense mutations (38/47) were predominant, most were de novo mutations (36/47), and a few were inherited from their fathers/mothers (6/47) or of unknown origin (5/47), with clinical manifestations of speech delay (43/47), growth retardation (43/47), intellectual disability (37/41), behavioral problems (37/47), facial malformations (34/47), skeletal malformations (23/47), obesity (16/47), skin abnormalities (11/47), etc. Thirty-nine cases were combined with seizures, 23 of whom were under control after treatment, and 8 cases were recorded as still having developmental backwardness after treatment. Conclusions:IDDSELD patients are rare at home and abroad, with diverse clinical phenotypes and difficult diagnosis. Symptomatic treatment is the main approach. And the patients can leave behind seizures and varying degrees of developmental backwardness. Among them, patients with 12q24.31 deletion are relatively rare and have not been reported in China, and this type is more common in females, all of whom have de novo mutations, and genetic testing is helpful for the early diagnosis of IDDSELD.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

Objective To find out the mechanism of strephenopodia and strephexopodia of children with spastic cerebral palsy by analyzing their gait character.MethodsForty children with spastic cerebral palsy and forty healthy children with normal walking ability were involved in this research.Footscan 7 gait analysis system was used to measure foot initial touchdown part,the ratio of different part touchdown phase to single supporting phase,the degree of strephenopodia and strephexopodia in different part.Two groups' characteristic parameters were analyzed by statistics method.ResultsSignificant differences were found in foot first touchdown part between two groups(P<0.05).The phenomenon that toes or metatarsus or whole foot first touch the earth was found in children with spastic cerebral palsy.The ratio of anterior foot and middle foot touchdown phase to single supporting phase were higher than normal children(P<0.05).In spastic cerebral palsy group the phenomenon of strephexopodia was more serious than strephenopodia during anterior foot touchdown phase.ConclusionLots of children with spastic cerebral palsy are suffering long-time compression pain and strephexopodia with anterior foot,active rectification must be performed during rehabilitation care.