CMTM6: A Critical Prognostic Indicator in Non-Small Cell Lung Cancer.

While CKLF-like MARVEL transmembrane domain containing 6 (CMTM6)'s role in stabilizing PD-L1 and immune evasion within tumors is established, its expression in lung cancer tissue and adjacent macrophages remains uncertain. The study aimed to elucidate this ambiguity by investigating CMTM6's role in non-small cell lung cancer (NSCLC) prognosis. Employing immunohistochemical staining on 141 NSCLC and 110 adjacent normal lung tissue samples, CMTM6 expression was evaluated using the HSCORE system. Interestingly, NSCLC exhibited significantly higher CMTM6 levels (161.04±86.60) compared to normal tissues (71.20±45.10) (p < 0.001), detected not only in cancer cells but also in macrophages, lymphocytes, and nearby bronchial epithelial cells. Stratifying patients by CMTM6 levels unveiled a correlation between heightened expression and poorer overall survival (p = 0.003), alongside a link to tumor-infiltrating lymphocytes (TIL) (p = 0.037), especially in cases with increased TIL. Multivariate analysis identified CMTM6 as an independent predictor of overall survival (p = 0.009), implying that elevated CMTM6 expression in NSCLC might signify an adverse prognostic marker for patient outcomes.

Repaglinide restrains HCC development and progression by targeting FOXO3/lumican/p53 axis.

PURPOSE: The recent focus on the roles of N-linked glycoproteins in carcinogenesis across various malignancies has prompted our exploration of aberrantly expressed glycoproteins responsible for HCC progression and potential therapeutic strategy. METHODS: Mass spectrometry was applied to initially identify abnormally expressed glycoproteins in HCC, which was further assessed by immunohistochemistry (IHC) staining. The role of selected glycoprotein on HCC development and underlying mechanism was systematically investigated by colony formation, mouse xenograft, RNA-sequencing and western blot assays, etc. Chromatin immunoprecipitation (ChIP) and luciferase assays were performed to explore potential transcription factors (TFs) of selected glycoprotein. The regulation of repaglinide (RPG) on expression of lumican and downstream effectors was assessed by western blot and IHC, while its impact on malignant phenotypes of HCC was explored through in vitro and in vivo analyses, including a murine NASH-HCC model established using western diet and carbon tetrachloride (CCl4). RESULTS: Lumican exhibited upregulation in both serum and tumor tissue, with elevated expression associated with an inferior prognosis in HCC patients. Knockdown of lumican resulted in significantly reduced growth of HCC in vitro and in vivo. Mechanically, lumican promoted HCC malignant phenotypes by inhibiting the p53/p21 signaling pathway. Forkhead Box O3 (FOXO3) was identified as the TF of lumican that transcriptionally enhanced its expression. Without silencing FOXO3, RPG blocked the binding of FOXO3 to the promoter region of lumican, thereby inhibiting the activation of lumican/p53/p21 axis. Mice treated with RPG developed fewer and smaller HCCs than those in the control group at 24 weeks after establishment. CONCLUSION: Our results indicate that RPG prevented the development and progression of HCC via alteration of FOXO3/lumican/p53 axis.

Nomogram for predicting postoperative pulmonary complications in spinal tumor patients.

OBJECTIVES: Although several independent risk factors for postoperative pulmonary complications (PPCs) after spinal tumor surgery have been studied, a simple and valid predictive model for PPC occurrence after spinal tumor surgery has not been developed. PATIENTS AND METHODS: We collected data from patients who underwent elective spine surgery for a spinal tumor between 2013 and 2020 at a tertiary hospital in China. Data on patient characteristics, comorbidities, preoperative examinations, intraoperative variables, and clinical outcomes were collected. We used univariable and multivariable logistic regression models to assess predictors of PPCs and developed and validated a nomogram for PPCs. We evaluated the performance of the nomogram using the area under the receiver operating characteristic curve (ROC), calibration curves, the Brier Score, and the Hosmer-Lemeshow (H-L) goodness-of-fit test. For clinical use, decision curve analysis (DCA) was conducted to identify the model's performance as a tool for supporting decision-making. RESULTS: Among the participants, 61 (12.4%) individuals developed PPCs. Clinically significant variables associated with PPCs after spinal tumor surgery included BMI, tumor location, blood transfusion, and the amount of blood lost. The nomogram incorporating these factors showed a concordance index (C-index) of 0.755 (95% CI: 0.688-0.822). On internal validation, bootstrapping with 1000 resamples yielded a bias-corrected area under the receiver operating characteristic curve of 0.733, indicating the satisfactory performance of the nomogram in predicting PPCs. The calibration curve demonstrated accurate predictions of observed values. The decision curve analysis (DCA) indicated a positive net benefit for the nomogram across most predicted threshold probabilities. CONCLUSIONS: We have developed a new nomogram for predicting PPCs in patients who undergo spinal tumor surgery.

Citrate synthase lysine K215 hypoacetylation contributes to microglial citrate accumulation and pro-inflammatory functions after traumatic brain injury.

AIMS: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation. METHODS: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment. RESULTS: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation. CONCLUSION: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.

The accuracy and reliability of different midsagittal planes in the symmetry assessment using cone-beam computed tomography.

Symmetry is an essential component of esthetic assessment. Accurate assessment of facial symmetry is critical to the treatment plan of orthognathic surgery and orthodontic treatment. However, there is no internationally accepted midsagittal plane (MSP) for orthodontists and orthognathic surgeons. The purpose of this study was to explore a clinically friendly MSP, which is more accurate and reliable than what is commonly used in symmetry assessment. Forty patients with symmetric craniofacial structures were analyzed on cone-beam computed tomography (CBCT) scans. The CBCT data were exported to the Simplant Pro software to build four reference planes that were constructed by nasion (N), basion (Ba), sella (S), odontoid (Dent), or incisive foramen (IF). A total of 31 landmarks were located to determine which reference plane is the most optimal MSP by comparing the asymmetry index (AI). The mean value of AI showed a significant difference (p < 0.05) among four reference planes. Also, the mean value of AI for all landmarks showed that Plane 2 (consisting of N, Ba, and IF) and Plane 4 (consisting of N, IF, and Dent) were more accurate and stable. In conclusion, the MSP consisting of N, Dent, and IF shows more accuracy and reliability than the other planes. Further, it is more clinically friendly because of its significant advantage in landmarking.

A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner.

Resistance to temozolomide (TMZ), the frontline chemotherapeutic agent for glioblastoma (GBM), has emerged as a formidable obstacle, underscoring the imperative to identify alternative therapeutic strategies to improve patient outcomes. In this study, we comprehensively evaluated a novel agent, O6-methyl-2'-deoxyguanosine-5'-triphosphate (O6-methyl-dGTP) for its anti-GBM activity both in vitro and in vivo. Notably, O6-methyl-dGTP exhibited pronounced cytotoxicity against GBM cells, including those resistant to TMZ and overexpressing O6-methylguanine-DNA methyltransferase (MGMT). Mechanistic investigations revealed that O6-methyl-dGTP could be incorporated into genomic DNA, disrupting nucleotide pools balance, and inducing replication stress, resulting in S-phase arrest and DNA damage. The compound exerted its anti-tumor properties through the activation of AIF-mediated apoptosis and the parthanatos pathway. In vivo studies using U251 and Ln229 cell xenografts supported the robust tumor-inhibitory capacity of O6-methyl-dGTP. In an orthotopic transplantation model with U87MG cells, O6-methyl-dGTP showcased marginally superior tumor-suppressive activity compared to TMZ. In summary, our research, for the first time, underscores the potential of O6-methyl-dGTP as an effective candidate against GBM, laying a robust scientific groundwork for its potential clinical adoption in GBM treatment regimens.

Colonic L-cell impairment in aged subjects with type 2 diabetes leads to diminished GLP-1 production.

AIMS: Glucagon-like peptide 1 (GLP-1) is produced by the L subtype of enteroendocrine cells (EECs). Patients with type 2 diabetes (T2D) exhibit reduced incretin effect, but the pathophysiology and functional change of the L-cells remain unclear. Deciphering the mechanisms of the biological changes in L-cells under T2D conditions may assist in the research of gut-based strategies for T2D therapy. METHODS: We investigated the fasting serum GLP-1 levels and the distribution of colonic L-cells in young and aged participants with and without T2D. Additionally, we established an aged male T2D Wistar rat model subjected to a long-term high-fat and high-fructose (HFHF) diet. Histological investigations and single-cell RNA sequencing (scRNA-seq) analyses were performed to explore the mechanisms underlying functional changes in the colonic EECs. RESULTS: We observed a decline in circulating GLP-1 levels and a reduced number of colonic L-cells in elderly patients with T2D. The mechanisms underlying impaired L-cell formation and disturbed GLP-1 production were revealed using aged T2D rats induced by a long-term HFHF diet. The scRNA-seq results showed that the transcription factors that regulate L-cell commitment, such as Foxa1, were downregulated, and the expression of genes that participate in encoding GLP-1, GLP-1 posttranslational processing, hormone secretion, and nutrient sensing was disturbed. CONCLUSIONS: Taken together, the reduced L-cell lineage commitment and disturbed L-cell functions might be the major cause of the reduced GLP-1 production in aged populations with T2D. Our study provides new insights for identifying novel targets in colonic L-cells for improving endogenous GLP-1 production.

Oculogyric crisis symptoms related to risperidone treatment: a case report.

BACKGROUND: Oculogyric crisis (OGC) is a rare focal dystonia of the ocular muscles that not only interferes with patients' medication adherence but also negatively affects the course and prognosis of the primary disease. Early detection and treatment of OGC can improve patients' medication adherence and quality of life. CASE PRESENTATION: This paper reports a case of a 19-year-old Asian female with a diagnosis of schizophrenia who was treated intermittently with atypical antipsychotics aripiprazole or risperidone for 2 years, with improvement of psychotic symptoms during the course of medication, and then developed double eye rolling and staring with irritability when treated with risperidone 4 mg/d or 6 mg/d. Then, we changed the medication to clozapine, and the patient's psychotic symptoms were controlled and stable. The symptoms of double eye rolling and gaze disappeared. CONCLUSION: Oculogyric crisis (OGC) is a rare focal dystonia of the oculogyric muscle. This case provides clinicians with a basis for the early recognition and management of oculogyric crisis during the use of atypical antipsychotics (risperidone).

A novel remnant liver-first strategy for liver autotransplantation in patients with end-stage hepatic alveolar echinococcosis: a retrospective case series.

BACKGROUND: Ex vivo liver resection combined with autotransplantation is an effective therapeutic strategy for unresectable end-stage hepatic alveolar echinococcosis (HAE). However, ex vivo liver resection combined with autotransplantation is a technically demanding and time-consuming procedure associated with significant morbidity and mortality. The authors aimed to present our novel remnant liver-first strategy of in vivo liver resection combined with autotransplantation (IRAT) technique for treating patients with end-stage HAE. METHODS: This retrospective study included patients who underwent IRAT between January 2014 and December 2020 at two institutions. Patients with end-stage HAE were carefully assessed for IRAT by a multidisciplinary team. The safety, feasibility, and outcomes of this novel technique were analyzed. RESULTS: IRAT was successfully performed in six patients, with no perioperative deaths. The median operative time was 537.5 min (range, 501.3-580.0), the median anhepatic time was 59.0 min (range, 54.0-65.5), and the median cold ischemia time was 165.0 min (range, 153.8-201.5). The median intraoperative blood loss was 700.0 ml (range, 475.0-950.0). In-hospital complications occurred in two patients. No Clavien-Dindo grade III or higher complications were observed. At a median follow-up of 18.6 months (range, 15.4-76.0) , all patients were alive. No recurrence of HAE was observed. CONCLUSION: The remnant liver-first strategy of IRAT is feasible and safe for selected patients with end-stage HAE. The widespread adoption of this novel technique requires further studies to standardize the operative procedure and identify patients who are most likely to benefit from it.

Genome and transcriptome analysis of Enterococcus faecium from intestinal colonization and Enterococcus faecium from urinary tract infection.

Introduction: Enterococcus faecium is a common pathogen responsible for urinary tract infections (UTIs) and often establishes extensive colonization within the intestinal tract. Our aim was to assess the genomic and transcriptomic differences between colonized E. faecium without UTI (only-colonization) and colonized E. faecium causing UTI (endogenous infections). Method: We investigated the correlation between fecal isolates from the same patient and UTI-causing isolates using PFGE and WGS, and classified fecal isolates into two groups: those that solely colonized and those associated with endogenous urinary tract infections. We characterized the genomes of colonization-only and endogenously infected isolates by Scoary GWAS, and the transcriptomes of the isolates at 3 h urine exposure to assess pathogen-related changes. Result: Based on PFGE and WGS, eight isolates of endogenously infected E. faecium and nine isolates of only-colonized E. faecium were characterized and carbon and nitrogen regulated metabolisms such as genes encoding the phosphotransferase (PTS) system were enriched in endogenously infected E. faecium. Transcriptome analysis revealed significant differences in gene expression in the PTS system, lysine synthesis, galactose metabolism and citrate import between endogenously infected and only-colonized E. faecium isolates, highlighting the important role of certain carbon regulatory genes in the colonization and survival of endogenously infected E. faecium. Conclusion: In only-colonized and endogenously infected isolates, we observed differential expression patterns of genes related to carbon metabolism and amino acids, suggesting that metabolic diversity is a strategy for isolates leading to endogenous infection.

Risk Factors for Hypocoagulability After Cardiac Surgery: A Retrospective Study.

Hemostatic disturbances after cardiac surgery can lead to excessive postoperative bleeding. Thromboelastography (TEG) was employed to evaluate perioperative coagulative alterations in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), investigating the correlation between factors concomitant with cardiac surgery and modifications in coagulation. Coagulation index as determined by TEG correlated significantly with postoperative bleeding at 24-72 h after cardiac surgery (P < .001). Among patients with a normal preoperative coagulation index, those with postoperative hypocoagulability showed significantly lower nadir temperature (P = .003), larger infused fluid volume (P = .003), and longer CPB duration (P = .033) than those with normal coagulation index. Multivariate logistic regression showed that nadir intraoperative temperature was an independent predictor of postoperative hypocoagulability (adjusted OR: 0.772, 95% CI: 0.624-0.954, P = .017). Multivariate linear regression demonstrated linear associations of nadir intraoperative temperature (P = .017) and infused fluid volume (P = .005) with change in coagulation index as a result of cardiac surgery. Patients are susceptible to hypocoagulability after cardiac surgery, which can lead to increased postoperative bleeding. Ensuring appropriate temperature and fluid volume during cardiac surgery involving CPB may reduce risk of postoperative hypocoagulability and bleeding.

Nadir Hemoglobin Concentration After Spinal Tumor Surgery: Association With Risk of Composite Adverse Events.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To explore the association of early postoperative nadir hemoglobin with risk of a composite outcome of anemia-related and other adverse events. METHODS: We retrospectively analyzed data from spinal tumor patients who received intraoperative blood transfusion between September 1, 2013 and December 31, 2020. Uni- and multivariate logistic regression was used to explore relationships of clinicodemographic and surgical factors with risk of composite in-hospital adverse events, including death. Subgroup analysis explored the relationship between early postoperative nadir hemoglobin and composite adverse events. RESULTS: Among the 345 patients, 331 (95.9%) experienced early postoperative anemia and 69 (20%) experienced postoperative composite adverse events. Multivariate logistic regression analysis showed that postoperative nadir Hb (OR = .818, 95% CI: .672-.995, P = .044), ASA ≥3 (OR = 2.007, 95% CI: 1.086-3.707, P = .026), intraoperative RBC infusion volume (OR = 1.133, 95% CI: 1.009-1.272, P = .035), abnormal hypertension (OR = 2.199, 95% CI: 1.085-4.457, P = .029) were correlated with composite adverse events. The lumbar spinal tumor was associated with composite adverse events with a decreased odds compared to thoracic spinal tumors (OR = .444, 95% CI: .226-.876, P = .019). Compared to patients with postoperative nadir hemoglobin ≥11.0 g/dL, those with nadir <9.0 g/dL were at significantly higher risk of postoperative composite adverse events (OR = 2.709, 95% CI: 1.087-6.754, P = .032). CONCLUSION: Nadir hemoglobin <9.0 g/dL after spinal tumor surgery is associated with greater risk of postoperative composite adverse events in patients who receive intraoperative blood transfusion.

Does depression affect the association between prosocial behavior and anxiety? A cross-sectional study of students in China.

Background: A growing number of studies have suggested that adolescents' prosocial behavior can protect against depression and anxiety. It is known that anxiety and depression are often comorbid. However, it remains unclear if when depression is present, prosocial behavior remains protective against anxiety, and if when anxiety is present, prosocial behavior remains protective against depression. The purpose of this study was to determine the association of anxiety and depressive with prosocial behavior. Methods: A large representative sample of middle-school students was recruited for a cross-sectional study and completed standardized instruments (the Children's Depression Inventory (CDI), Screen for Child Anxiety Related Emotional Disorders-Child version (SCARED-C), and Strengths and Difficulties Questionnaire (SDQ)). We used structural equation modeling (SEM) to examine the protective effect of prosocial behavior against anxiety when depression was present. Results: A survey of 3,510 students was conducted, and the final analysis included 3,169 students, comprising 1,616 boys (51.0%) and 1,553 girls (49.0%), with a mean age of 13.09 years (SD = 1.31, range 11-16).The prevalence rates of anxiety and depression in early adolescents were 31.6 and 16.7%, respectively. More than two-thirds of depressed adolescents had comorbid anxiety, while more than one-third of anxious adolescents had comorbid depression. Regression models showed that compared with depressed adolescents, adolescents without depressive symptoms exhibited a significant negative correlation between prosocial behaviors and anxiety and depression (ß = -0.01, p > 0.01, ß = -0.06, p > 0.01; ß = -0.11, p < 0.01, and ß = -0.17, p < 0.01). There was no difference in the relationship between prosocial behavior and depression between anxious and non-anxious adolescents (p > 0.05). Conclusion: Anxiety and depression are common in adolescence and are often comorbid disorders. However, the comorbidity is not symmetrical. Specifically, the protective effect of prosocial behavior against anxiety is weaker in depressed adolescents. Findings are discussed in light of related research and theory, and insights for intervention programs and future research are presented.

Antibacterial lanostane triterpenoids from Ganoderma tsugae.

A phytochemical investigation on the 80% EtOH extract of the fruiting bodies of Ganoderma tsugae resulted into the isolation of two previously undescribed lanostane triterpenoids, 7,11-dioxo-3ß-acetyloxy-26,27-dihydroxy-lanosta-8,24-diene (1) and 7,20-dioxo-3ß-acetyloxy-11ß,15α-dihydroxy-22,23,24,25,26,27-hexanorlanosta-8-ene (2), togeher with one known lanostane triterpenoid ganodermanontriol (3). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the triterpenoids were in vitro evaluated for their antibacterial activities against six pathogenic microorganisms. Compound 3 exhibited some activities against three Gram positive bacteria with MIC values less than 30 µg/ml.

Reliability and accuracy of a semi-automatic segmentation protocol of the nasal cavity using cone beam computed tomography in patients with sleep apnea.

OBJECTIVES: The objectives of this study included using the cone beam computed tomography (CBCT) technology to assess: (1) intra- and inter-observer reliability of the volume measurement of the nasal cavity; (2) the accuracy of the segmentation protocol for evaluation of the nasal cavity. MATERIALS AND METHODS: This study used test-retest reliability and accuracy methods within two different population sample groups, from Eastern Asia and North America. Thirty obstructive sleep apnea (OSA) patients were randomly selected from administrative and research oral health data archived at two dental faculties in China and Canada. To assess the reliability of the protocol, two observers performed nasal cavity volume measurement twice with a 10-day interval, using Amira software (v4.1, Visage Imaging Inc., Carlsbad, CA). The accuracy study used a computerized tomography (CT) scan of an OSA patient, who was not included in the study sample, to fabricate an anthropomorphic phantom of the nasal cavity volume with known dimensions (18.9 ml, gold standard). This phantom was scanned using one NewTom 5G (QR systems, Verona, Italy) CBCT scanner. The nasal cavity was segmented based on CBCT images and converted into standard tessellation language (STL) models. The volume of the nasal cavity was measured on the acquired STL models (18.99 ± 0.066 ml). RESULTS: The intra-observer and inter-observer intraclass correlation coefficients for the volume measurement of the nasal cavity were 0.980-0.997 and 0.948-0.992 consecutively. The nasal cavity volume measurement was overestimated by 1.1%-3.1%, compared to the gold standard. CONCLUSIONS: The semi-automatic segmentation protocol of the nasal cavity in patients with sleep apnea and by using cone beam computed tomography is reliable and accurate. CLINICAL RELEVANCE: This study provides a reliable and accurate protocol for segmentation of nasal cavity, which will facilitate the clinician to analyze the images within nasoethmoidal region.

Stress distribution of the modified clear twin-block aligner on the temporomandibular joint, alveolar bone and teeth: A finite element analysis.

OBJECTIVE: The modified clear twin-block aligner (CTBA) was developed to provide a mandibular advancement appliance for the treatment of mandibular retrognathia. The objective of this study was to analyse the stress distribution changes of CTBA with 45°, 60° and 70° bite blocks. MATERIAL AND METHODS: A three-dimensional model of the craniomaxillofacial bones and teeth was generated from a spiral computed tomography (CT) scan. The models of the articular disc, capsule, periodontal ligament and CTBA were constructed mathematically. After assigning the appropriate material properties and the boundary condition using ABAQUS software, we simulated the CTBA with different bite blocks to analyse the mechanical effects. RESULTS: In the temporomandibular joint (TMJ) region, the posterior aspect of the condyle and glenoid fossa experienced tensile stress that was approximately about 22 times greater at 70° than at 45°. The Von Mises stress distribution on the articular disc tended to be uniform. The strain direction of the condyle was backward. In the maxillary bone, the stress on the labial alveolar bone was about 5.83MPa at 70° and greater than that on the lingual side. The resulting displacement of the dentition revealed a tendency for the upper teeth to shift backward and the lower teeth to move forward by 0.46 to 0.49mm. The foregoing stress and displacement rose as the angle of the bite blocks increased. CONCLUSIONS: CTBA with 70° bite blocks constituted an advantageous biomechanical setting for the treatment of mandibular retrognathia in teenagers and provided a superior therapeutic effect.

A case report of a novel HIST1H1E mutation and a review of the bibliography to evaluate the genotype-phenotype correlations.

BACKGROUND: HIST1H1E is a member of the H1 gene family. Excess de novo likely gene-disruptive variants involving the C-terminal tail of HIST1H1E have been reported in neurodevelopmental disorders. Although clinical phenotypes in some patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with HIST1H1E variants. METHODS: Whole-exome sequencing (WES) was performed on the proband. The variant was validated using Sanger sequencing in both proband and parents. Published HIST1H1E variants in neuropsychiatric disorders were reviewed. RESULTS: Herein, we reported a new de novo frameshift mutation in HIST1H1E (NM_005321.2, c.416_419dupAGAA, p.Ala141GlufsTer56) in an individual with Rahman syndrome. To explore the genotype-phenotype correlations for HIST1H1E variants in neurodevelopmental disorders, we comprehensively curated and summarized 23 variants and the clinical features from 52 patients. Our findings revealed that likely gene-disrupting variants in HIST1H1E contribute to a wide range of neurodevelopmental phenotypes. We observed the common phenotypes including craniofacial features, ID, hypotonia, and autism/behavior problem in patients with HIST1H1E variants. While the different genotypes corresponding to different phenotypes or the same phenotype were also observed. CONCLUSION: These data provide scientific evidence for the genetic diagnosis and precision clinical management.