ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

To investigate the positivity rates of specific antibodies, including parietal cell antibody (PCA) and anti-inner factor antibody (IFA), in a community population in Xinjiang for autoimmune gastritis (AIG), determine the prevalence of AIG, and analyze the correlations of PCA and IFA with clinical characteristics, pepsinogen (PG), gastrin 17 (G17), and Helicobacter pylori antibody (Hp-Ab).

ObjectiveTo establish the mouse models of psoriasis-like lesions induced by continuous cold exposure or intermittent cold exposure combined with imiquimod （IMQ）， and to evaluate the interventional effects of Kaixuan Jiedu core prescription （KXJD） on the two models. MethodsMale C57BL/6J mice were selected and classified into two experimental batches. The first batch of 36 mice was randomized into a room temperature group， a continuous cold exposure （10 ℃/24 h） group， and an intermittent cold exposure （10 ℃/6 h） group. Each group was further divided into a normal subgroup and a model subgroup （topical application of IMQ to induce skin lesions）， with 6 mice in each subgroup， for modeling and evaluation. The second batch of 54 mice， with 6 in each group， were subjected to the same temperature grouping with an additional KXJD （30.42 g·kg^-1， continuous gavage for 5 days） group. Comprehensive evaluation of model characteristics and KXJD efficacy was conducted through Psoriasis Area and Severity Index （PASI） scoring， skin temperature measurement by infrared thermography， histopathological observation by hematoxylin-eosin （HE） staining， detection of vascular endothelial growth factor （VEGF） and platelet endothelial cell adhesion molecule 1 （CD31） by immunohistochemistry， detection of Claudin-1 and Occludin by immunofluorescence assay， determination of serum levels of tumor necrosis factor-α （TNF-α） and interleukin （IL）-10 by enzyme-linked immunosorbent assay （ELISA）， and quantification of mRNA levels of IL-17A， IL-23， IL-6， and chemokine ligand 20 （CCL20） in skin lesions by quantitative Real-time polymerase chain reaction （Real-time PCR）. ResultsModel mice in all temperature groups exhibited typical psoriasis-like skin lesions. Compared with the normal groups， the model groups showed increased PASI scores， decreased skin temperatures （P<0.05）， obvious epidermal thickening， parakeratosis， and dermal inflammatory cell infiltration， as well as elevated mRNA levels of IL-17A， IL-23， IL-6， and CCL20 （P<0.05）. Cold exposure further aggravated psoriasis. The total PASI score of the intermittent cold exposure model group was higher than that of the room temperature model group （P<0.05）. The serum IL-10 did not show a compensatory elevation， and the blood vessels presented a characteristic of elevated CD31 expression （P<0.05） without a synchronous increase in VEGF. The continuous cold exposure model group exhibited more significant dermal capillary tortuosity and dilation， with the highest mRNA levels of IL-17A， IL-23， IL-6， and CCL20 among all groups. Compared with the respective model groups， KXJD intervention alleviated skin lesions， reduced epidermal thickness and inflammatory cell infiltration， and increased skin temperature， with the temperature increase being particularly significant in the intermittent cold exposure+KXJD group （P<0.05）. Furthermore， KXJD down-regulated the expression of VEGF and CD31， restored the expression of Claudin-1 and Occludin， decreased the mRNA levels of IL-17A and IL-23 （P<0.05）， and reduced the serum TNF-α level. ConclusionThis study successfully established compound psoriasis-like mouse models induced by cold exposure combined with IMQ. It confirms that cold aggravates the severity of psoriasis by exacerbating the closure of Xuanfu （sweat pores）， microcirculation disorders， and immune imbalance. Moreover， different cold exposure patterns have distinct mechanism differences. Continuous cold exposure focuses on enhancing the inflammatory response via the IL-23/IL-17 axis and angiogenesis， simulating chronic aggravation under a long-term cold environment. Intermittent cold exposure tends to impair immune regulation and induce microvascular endothelial stress， corresponding to acute exacerbations caused by sudden temperature drops. KXJD can effectively alleviate psoriasis-like skin lesions under cold conditions by unblocking Xuanfu， regulating vasomotor function， and correcting abnormal immune-inflammatory responses.

ObjectiveTo investigate the ameliorative effects of Kaixuan Jiedu core prescription （KXJD） on skin lesions in psoriasis-like mouse models under cold environment exposure， and to analyze its influences on transient receptor potential （TRP） channels and related neuroimmune regulatory factors. MethodsThirty-six C57BL/6J mice were randomized into 6 groups， with 6 mice in each group. Two feeding conditions were set： Normal temperature and cold ［simulating a cold environment at （10±0.5） ℃， for 6 h daily］. Mice were induced to develop psoriasis-like lesions by applying imiquimod externally. The model mice were allocated into model groups and KXJD （30.42 g·kg^-1， continuous gavage for 5 days） groups. Normal mice were used as the control group. Specifically， mice were allocated into normal temperature， normal temperature model， normal temperature+KXJD， cold exposure control， cold exposure model， and cold exposure+KXJD groups. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining. The expression of cluster of differentiation （CD） 3⁺ T lymphocytes， CD11c⁺ dendritic cells （DCs）， phosphorylated extracellular signal-regulated kinase （p-ERK）， and substance P （SP） were detected by immunofluorescence assay. The protein level of transient receptor potential cation channel subfamily M member 8 （TRPM8） in the skin tissue was determined by Western blot. The expression of TRPM8， transient receptor potential cation channel subfamily V member 1 （TRPV1）， transient receptor potential cation channel subfamily A member 1 （TRPA1）， and transient receptor potential cation channel subfamily V member 2 （TRPV2） at the protein and mRNA levels was determined by immunohistochemistry and Real-time PCR， respectively. The levels of calcitonin gene-related peptide （CGRP） and neuropeptide Y （NPY） in the serum were analyzed by enzyme-linked immunosorbent assay （ELISA）. The enrichment analysis of differentially expressed genes （DEGs） and TRP pathway network construction were conducted based on the GEO database. The co-expression of TRPM8 and CGRP in the skin lesions was verified by immunofluorescence double labeling. ResultsBoth the normal temperature and cold exposure model groups showed typical psoriasis-like skin lesions. Compared with the normal temperature and cold exposure control groups， the model groups had excessive epidermal keratinization， thickened spinous layer， and inflammatory infiltration in the dermis， with increased pathological scores （P<0.05）， increased infiltration of CD3⁺ and CD11c⁺ cells and expression of p-ERK and SP， upregulated mRNA levels of TRPM8， TRPA1， and TRPV2， downregulated mRNA level of TRPV1 （P<0.05）， and reduced content of CGRP and increased content of NPY in the serum. Compared with the normal temperature and cold exposure model groups， KXJD reduced the pathological manifestations and pathological scores of psoriasis-like skin lesions （P<0.05）， and inhibited the infiltration of CD3⁺ and CD11c⁺ cells and the expression of p-ERK and SP. Gene enrichment analysis suggested that the DEGs of psoriasis were significantly enriched in the interleukin （IL）-17 signaling pathway and TRP channel inflammatory regulation. Compared with the normal temperature and cold exposure model groups， KXJD reversed the abnormal mRNA levels of genes related to the TRP channel subfamilies （P<0.05）， increased the CGRP level， and decreased the NPY level. Immunofluorescence double labeling further confirmed that compared with the model groups， KXJD down-regulated the co-expression of TRPM8 and CGRP in the skin lesions. ConclusionKXJD may ameliorate psoriasis-like skin lesions by downregulating the overexpressed cold-sensitive receptor TRPM8 in skin lesions and correcting the disorder of neuropeptide （such as SP and CGRP） release mediated by it， thereby inhibiting the IL-23/helper T cell 17 （Th17） core inflammatory pathway， suppressing the infiltration of inflammatory cells and the activation of the ERK signaling pathway， and regulating the Xuanfu （sweat pore）-TRPM8-neuroimmune response axis.

ObjectiveTo investigate the ameliorative effects and mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroimmunological inflammation in imiquimod （IMQ）-induced psoriasis-like mice. MethodsA total of 24 C57BL/6J mice were randomly divided into four groups （n=6）： Normal， model， KXJD， and tropomyosin receptor kinase A （TrkA） inhibitor GW441756 groups. The mice in the model， KXJD， and GW441756 groups were topically treated with 5% IMQ cream （62.5 mg·d^-1） on the back to induce psoriasis-like inflammation. The KXJD group received KXJD by gavage （30.42 g·kg^-1）， the GW441756 group received intraperitoneal injection of GW441756 （10 mg·kg^-1）， and the normal and model groups received an equal volume of normal saline by gavage， with continuous intervention for 5 days. The severity of skin lesions was evaluated using the psoriasis area and severity index （PASI）. Hematoxylin-eosin （HE） staining was used to measure epidermal thickness and observe pathological changes in the lesioned skin. Immunohistochemistry was employed to detect the expression of proliferating cell nuclear antigen （Ki67） and interleukin-17A （IL-17A） in the lesioned skin. Enzyme-linked immunosorbent assay （ELISA） was used to quantify the levels of interleukin-23 （IL-23） and calcitonin gene-related peptide （CGRP） in the lesioned tissues. Western blot was used to detect the expression of TrkA and phosphorylated TrkA （p-TrkA）. Immunofluorescence assay was performed to detect the expression of TrkA receptor， protein gene product 9.5 （PGP9.5）， cluster of differentiation 11c （CD11c）， and CGRP in the lesions. Flow cytometry was used to detect the activation of splenic dendritic cells （DCs）. ResultsCompared with the normal group， the model group exhibited typical psoriasis-like inflammation， characterized by erythema， infiltration and scaling， with histopathological findings of epidermal hyperkeratosis and acanthosis. The model group showed significantly increased expression of Ki67， IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， increased fluorescence intensity of CD11c， and significantly decreased CGRP expression （P<0.05）. The splenic DC activation was significantly enhanced， as indicated by the increased mean fluorescence intensity （MFI） of CD86 （P<0.05）. Compared with the model group， both the KXJD and GW441756 groups showed amelioration of the psoriasis-like skin inflammation， with significantly down-regulated expression of IL-17A， IL-23 and p-TrkA （P<0.05， P<0.01）， significantly up-regulated expression of CGRP （P<0.01）， reduced CD11c⁺ DC infiltration， and restored splenic DC activation balance （down-regulated CD86 MFI and up-regulated CD80 and CD40 MFI）. Furthermore， the inhibitory effect of KXJD on Ki67 was significantly superior to that of the GW441756 group （P<0.01）. ConclusionKXJD may alleviate IMQ-induced psoriasis-like inflammation in mice by targeting and inhibiting TrkA receptor phosphorylation， regulating CGRP expression in the lesions， and ameliorating aberrant activation of dendritic cells， while also significantly inhibiting keratinocyte proliferation.

ObjectiveTo investigate the effects and molecular mechanisms of Kaixuan Jiedu core prescription （KXJD） on neuroinflammation and immuno-inflammation in the mouse model of imiquimod （IMQ）-induced psoriasis-like skin lesions by regulating the nerve growth factor （NGF）-tropomyosin receptor kinase A （TrkA）/transient receptor potential vanilloid 1 （TRPV1）-protease-activated receptor-2 （PAR-2） signaling pathway. MethodsA psoriasis-like skin lesion model was established in male C57BL/6J mice with IMQ. A total of 24 mice were randomized into four groups （n=6 per group）： Blank control， model， methotrexate （MTX， 1 mg·kg^-1）， and KXJD （30.42 g·kg^-1）. Immunohistochemistry was employed to detect the expression of cluster of differentiation 3 （CD3）， EGF-like module-containing mucin-like hormone receptor-like 1 （F4/80）， lymphocyte antigen 6 complex locus G （Ly-6G）， substance P （SP）， calcitonin gene-related peptide （CGRP）， NGF， phosphorylated TrkA （p-TrkA）， phosphorylated TRPV1 （p-TRPV1）， and PAR-2 in skin lesions. Serum levels of interleukin-17A （IL-17A） and interleukin-23 （IL-23） were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence assay and Western blot were employed to determine the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65）. Reverse transcription quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA levels of interleukin-1β （IL-1β）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and C-X-C motif chemokine ligand 1 （CXCL1） in skin lesions. Correlation analysis was performed. ResultsCompared with the blank control group， the model group showed increased positive areas of CD3⁺， F4/80⁺， and Ly-6G⁺ in skin lesions （P<0.05）， elevated serum levels of IL-17A and IL-23 （P<0.05）， increased positive areas of SP and CGRP in skin lesions （P<0.05）， increased positive areas of NGF， p-TrkA， p-TRPV1， and PAR-2 （P<0.05）， elevated ratios of p-p38 MAPK/p38 MAPK and p-NF-κB p65/NF-κB p65 （P<0.05）， and upregulated mRNA levels of IL-1β， TNF， IL-6， and CXCL1 （P<0.05）. Compared with those in the model group， all the above indicators were reversed in the KXJD group （P<0.05）. MTX only downregulated the expression of p-TRPV1 and PAR-2 （P<0.05）， with no significant effects on the expression of NGF， p-TrkA， or CGRP. ConclusionKXJD inhibits the NGF-TrkA/TRPV1-PAR-2 signaling pathway to reduce neuropeptide release and simultaneously downregulates the p38 MAPK/NF-κB signaling pathway and the expression of downstream pro-inflammatory factors to ameliorate psoriasis-like neuroinflammation and immuno-inflammation. The therapeutic effect of KXJD on psoriasis-like inflammation is closely associated with the inhibition of the NGF-TrkA/TRPV1-PAR-2 signaling pathway. This study provides experimental evidence for the modern interpretation of the Xuanfu theory.

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.

Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.