[Effect of autologous platelet-rich plasma perfusion on cytokines in uterine drainage fluid of patients with intrauterine adhesions following hysteroscopic adhesiolysis].

Objective: To investigate the effect of autologous platelet-rich plasma (PRP) perfusion on the levels of cytokines in uterine drainage fluid in patients with moderate to severe intrauterine adhesions (IUA) following hysteroscopic adhesiolysis. Methods: Thirty patients with moderate to severe IUA who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University from November 2020 to March 2021 were randomly divided into two groups: the PRP group (15 patients with placement of intrauterine-suitable balloons and PRP infusion) and the control group (15 patients with placement of intrauterine-suitable balloons only). For all patients, the channel switch was opened 48 hours after the surgery. The drainage fluid of the uterine cavity was collected using syringes through the proximal end of the drainage channel switch at 24 hours after the surgery and through the drainage channel directly at 48, 72, 96, and 120 hours after the surgery, and the levels of related cytokines including platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1) and transforming growth factor-ß1 (TGF-ß1) in the drainage fluid of the uterine cavity were evaluated, respectively. Results: (1) The changes in volumes of uterine cavity drainage fluid: the total drainage fluid volumes of the PRP group and the control group in 120 hours after the surgery were (21.8±2.9) and (22.7±2.7) ml, respectively, and there was no statistically significant difference between the two groups (t=-0.847, P>0.05). No significant differences were found in the volumes of drainage fluid between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). (2) Variation in cytokine levels in the uterine cavity drainage fluid: ① PDGF-BB: median PDGF-BB levels at 24 and 48 hours after the surgery in the PRP group (6.6 and 9.6 µg/L, respectively) were significantly higher than those in the control group (4.7 and 2.7 µg/L, respectively; all P<0.05). There were no significant differences in PDGF-BB levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ② VEGF-A: median VEGF-A levels at 24 and 48 hours after the surgery in the PRP group (3.5 and 2.8 µg/L, respectively) were significantly higher than those in the control group (1.6 and 1.2 µg/L, respectively; all P<0.05). There were no significant differences in VEGF-A levels between the two groups at 72, 96, and 120 hours after the surgery (all P>0.05). ③ IGF-1: median IGF-1 level at 48 hours after the surgery in the PRP group was significantly higher than that in the control group (39.5 vs 8.6 µg/L, P<0.05). No significant differences were found in IGF-1 levels at 24, 72, 96, and 120 hours after the surgery between the two groups (all P>0.05). ④ TGF-ß1: There were no significant differences in TGF-ß1 levles between the two groups at 24, 48, 72, 96, and 120 hours after the surgery (all P>0.05). Conclusions: PRP perfusion following hysteroscopic adhesiolysis may increase the levels of PDGF-BB, VEGF-A, and IGF-1 in the uterine cavity drainage fluid, which plays a beneficial role in improving wound microvascular formation, reducing adhesion reformation, and promoting endometrial regeneration and repair.

Loss of Sigma-2 Receptor/TMEM97 Is Associated with Neuropathic Injury-Induced Depression-Like Behaviors in Female Mice.

Previous studies have shown that ligands that bind to sigma-2 receptor/TMEM97 (s2R/TMEM97), a transmembrane protein, have anxiolytic/antidepressant-like properties and relieve neuropathic pain-like effects in rodents. Despite medical interest in s2R/TMEM97, little affective and pain behavioral characterization has been done using transgenic mice, which limits the development of s2R/TMEM97 as a viable therapeutic target. Using wild-type (WT) and global Tmem97 knock-out (KO) mice, we sought to identify the contribution of Tmem97 in modulating affective and pain-like behaviors using a battery of affective and pain assays, including open field, light/dark preference, elevated plus maze, forced swim test, tail suspension test, and the mechanical sensitivity tests. Our results demonstrate that female Tmem97 KO mice show less anxiety-like and depressive-like behaviors in light/dark preference and tail suspension tests but not in an open field, elevated plus maze, and forced swim tests at baseline. We next performed spared nerve injury in WT and Tmem97 KO mice to assess the role of Tmem97 in neuropathic pain-induced anxiety and depression. WT mice, but not Tmem97 KO mice, developed a prolonged neuropathic pain-induced depressive-like phenotype when tested 10 weeks after nerve injury in females. Our results show that Tmem97 plays a role in modulating anxiety-like and depressive-like behaviors in naive animals with a significant change in the presence of nerve injury in female mice. Overall, these data demonstrate that Tmem97 could be a target to alleviate affective comorbidities of pain disorders.

Genome-wide association analysis of eggshell color of an F2 generation population reveals candidate genes in chickens.

Eggshell color is an important visual characteristic that affects consumer preferences for eggs. Eggshell color, which has moderate to high heritability, can be effectively enhanced through molecular marker selection. Various studies have been conducted on eggshell color at specific time points. However, few longitudinal data are available on eggshell color. Therefore, the objective of this study was to investigate eggshell color using the Commission International de L'Eclairage L*a*b* system with multiple measurements at different ages (age at the first egg and at 32, 36, 40, 44, 48, 52, 56, 60, 66, and 72 weeks) within the same individuals from an F2 resource population produced by crossing White Leghorn and Dongxiang Blue chicken. Using an Affymetrix 600 single nucleotide polymorphism (SNP) array, we estimated the genetic parameters of the eggshell color trait, performed genome-wide association studies (GWASs), and screened for the potential candidate genes. The results showed that pink-shelled eggs displayed a significant negative correlation between L* values and both a* and b* values. Genetic heritability based on SNPs showed that the heritability of L*, a*, and b* values ranged from 0.32 to 0.82 for pink-shelled eggs, indicating a moderate to high level of genetic control. The genetic correlations at each time point were mostly above 0.5. The major-effect regions affecting the pink eggshell color were identified in the 10.3-13.0 Mb interval on Gallus gallus chromosome 20, and candidate genes were selected, including SLC35C2, PCIF1, and SLC12A5. Minor effect polygenic regions were identified on chromosomes 1, 6, 9, 12, and 15, revealing 11 candidate genes, including MTMR3 and SLC35E4. Members of the solute carrier family play an important role in influencing eggshell color. Overall, our findings provide valuable insights into the phenotypic and genetic aspects underlying the variation in eggshell color. Using GWAS analysis, we identified multiple quantitative trait loci (QTLs) for pink eggshell color, including a major QTL on chromosome 20. Genetic variants associated with eggshell color may be used in genomic breeding programs.

Quercetin ameliorates lipid deposition in primary hepatocytes of the chicken embryo.

1. The accumulation of excessive fat plays a role in the development of non-alcoholic fatty liver disease (NAFLD) and phytogenic feed additives have the potential to ameliorate this. This study involved the isolation and culture of primary hepatocytes from chicken embryos to establish a model of hepatic steatosis induced by oleic acid/dexamethasone (OA/DEX). Lipid accumulation and cell viability were assessed using Nile Red staining, Oil Red O staining and cell count Kit -8 (CCK8) following treatment with varying concentrations of quercetin (Que). The potential mechanism by which Que exerts its effects was preliminarily investigated.2. The results indicated that OA effectively treated lipid accumulation in hepatocytes. There was no notable variance in cell proliferation between the normal and OA/DEX groups when subjected to Que treatment at concentrations of 1000 ng/ml and 10 000 ng/ml. Triglycerides and cholesterol (low and high density) decreased with Que treatment, with the most substantial reduction observed at 10 000 ng/ml.3. Gene expression levels decreased to levels similar to those in the control groups. Western blot data demonstrated that sterol regulatory element-binding protein 1 (SREBP-1) protein expression correlated with its mRNA expression level. Que mitigated lipid accumulation through the alpha serine/threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) pathways. Expression levels of lipid-related genes (APOB, PPARα, CYP3A5 and SREBP-1) decreased to levels similar to the control groups. Western blot data demonstrated that the SREBP-1 protein expression correlated with its mRNA expression level.4. Supplementation with Que ameliorated lipid accumulation through AKT and ERK signalling pathway in OA/DEX-induced high-fat hepatocytes.

[Research progress in regional odontodysplasia].

Regional odontodysplasia (ROD) is a rare localized dental developmental anomaly. The typical clinical manifestations of ROD are abnormal tooth eruption, abnormal development of enamel and dentin. The radiographic characteristic is "ghost teeth". Its etiology still remains unknown. The care and treatment of a patient with ROD needs a multidisciplinary approach. And the treatment should be taken after the assessment of each individual case of ROD. This paper reviews the definition, etiology, epidemiological features, clinical manifestations, imaging features, dental microstructure and treatment strategies of ROD to provide reference for clinical diagnosis and treatment.

[High expression of COX6B2 in gastric cancer is associated with poor long-term prognosis and promotes cell proliferation and cell cycle progression by inhibiting p53 signaling].

OBJECTIVE: To investigate the effect of COX6B2 expression in gastric cancer tissues on the patients' long-term prognosis and its underlying mechanism. METHODS: Based on the public databases and the medical records of patients, we analyzed the expression level of COX6B2 in gastric cancer and adjacent tissues and its influence on long-term prognosis of the patients. Enrichment analysis were used to predict the possible role of COX6B2 in gastric cancer. The effects of lentivirusmediated COX6B2 knockdown on biological behaviors of gastric cancer cells were examined using CCK-8 assay, flow cytometry, and Western blotting. RESULTS: TCGA database and the results of immunohistochemistry, Western blotting and realtime PCR all demonstrated a significantly higher expression of COX6B2 in gastric cancer tissues (P < 0.05). Kaplan-Meier plotter database and Kaplan-Meier curves showed that the patients with high COX6B2 expression had significantly shorter postoperative survival (P < 0.05). A high expression of COX6B2 in gastric cancer tissues was closely correlated with clinicopathologic stage, CEA and CA19-9 (P < 0.05). A high expression of COX6B2, CEA level≥5 µg/L and CA19-9 level≥37 kU/L were independent risk factors affecting postoperative 5-year survival rate of gastric cancer patients (P < 0.05), and COX6B2 expression level had a predictive value for long-term prognosis of the patients (P < 0.05). GO and KEGG enrichment analyses showed that COX6B2 was mainly involved in the regulation of cell cycle. In the in vitro cell experiment, COX6B2 overexpression significantly promoted gastric cancer cell proliferation, increased the percentage of G1/S phase cells and inhibited the cellular expressions of p53 and p21 (P < 0.05). CONCLUSION: s COX6B2 is highly expressed in gastric cancer and is closely correlated with a poor long-term prognosis of the patients possibly by promoting gastric cancer cell proliferation and regulating cell cycle.

Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.

Biological Properties of 3D-Printed Zirconia Implants with p-Cell Structures.

Research on 3-dimensional (3D) printed porous zirconia-based dental implants is still in its infancy. This study aimed to evaluate the biological responses of novel zirconia implants with p-cell structures fabricated by 3D printing. The solid zirconia samples exhibited comparable density, 3-point flexural strength, and accelerated aging properties compared to specimens prepared previously by conventional methods. Cell-based experiments showed that the p-cell structure promoted cell proliferation, adhesion, and osteogenesis-related protein expression. Mechanical tests showed that both p-cell and control implants could withstand a torque of 35 Ncm without breaking. The mean maximum breaking loads of p-cell and control implants were 1,222.429 ± 115.591 N and 1,903.857 ± 250.673 N, respectively, which were much higher than the human physiological chewing force and human mean maximum occlusal force. An animal experiment showed that the bone trabeculae around the implants were significantly thicker, more numerous, and denser in the p-cell group than in the control group. This work could provide promising guidance for further exploring 3D printing techniques for porous zirconia bionic implants in dentistry.

Predictive value of crossover sign for outcome of ultrasound-guided vacuum aspiration in women with Cesarean scar pregnancy.

OBJECTIVE: To examine the value of the crossover sign (COS) in predicting treatment outcome in women with a Cesarean scar pregnancy (CSP) who were treated with ultrasound-guided vacuum aspiration. METHODS: This was a retrospective cohort study of women with CSP who underwent ultrasound-guided vacuum aspiration. Based on the relationship between the gestational sac, Cesarean scar and anterior wall of the uterus, CSPs were classified by COS type. Analysis was conducted to investigate the association between COS type (COS-1, COS-2) and treatment outcome. The incidence of treatment failure, retained pregnancy tissue, secondary therapy and bleeding ≥ 200 mL were analyzed. RESULTS: In total, 181 eligible patients with CSP, including 90 (49.7%) women with COS-1 and 91 (50.3%) women with COS-2, were analyzed. COS-1 patients had a higher incidence of treatment failure compared with COS-2 patients (25.6% vs 8.8%; P = 0.003), as well as higher rates of retained pregnancy tissue (18.9% vs 6.6%; P = 0.013), secondary therapy (20.0% vs 6.6%; P = 0.002) and bleeding of ≥ 200 mL (13.3% vs 4.4%; P = 0.034). COS-1 and a large gestational sac (30.1-50.0 mm or >50.0 mm in diameter) were associated independently with increased risk of treatment failure (odds ratio, 4.57 (95% CI, 1.66-12.56); P = 0.003, 4.34 (95% CI, 1.35-13.94); P = 0.014 and 10.50 (95% CI, 2.54-43.46); P = 0.001, respectively). CONCLUSIONS: Ultrasound evaluation of the relationship between the gestational sac and the endometrial line (COS classification) in women with CSP may help to predict treatment outcome among those undergoing vacuum aspiration. Among COS-1 patients, especially those with a gestational sac diameter of >30.0 mm, vacuum aspiration may be discouraged. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Interaction of smoking and aging on emphysema and small airways disease in asymptomatic healthy men by CT-based parametric response mapping analysis.

AIM: To explore whether small airway disease and emphysema were affected by the interaction between smoking and aging on chest computed tomography (CT) images of asymptomatic healthy men analysed using a quantitative imaging tool parametric response mapping (PRM). MATERIALS AND METHODS: In this retrospective study, 95 asymptomatic healthy men underwent biphasic chest CT. The PRM classifies lung as a percentage of normal (PRMNormal%), functional small airway disease (PRMfSAD%), and emphysema (PRMEmph%). The patients were divided into groups based on their age and smoking status. Multiple linear regression analysis was applied to explore the factors influencing lung injury. Simple effects analysis was performed to explore the interaction between different age groups and smoking status. RESULTS: The interaction between aging and smoking significantly affected PRMfSAD% and PRMEmph% (p<0.001). The age range 60-69 and smoking were associated with increased PRMfSAD% and PRMEmph% (p<0.05). Futher stratification into different age subgroups showed that smoking was associated with increased PRMfSAD% and PRMEmph% in the 50-59 year age group. Besides, smoking in the 50-59 and 60-69 years group was associated with decreased PRMNormal%, while smoking in the 60-69 years group did not significantly influence the prevalence of PRMfSAD% and PRMEmph% (p>0.05). CONCLUSIONS: PRM reveals the interplay between smoking and aging in the development of lung injury in asymptomatic healthy men. Aging and smoking are important factors of emphysema and small airway disease in the 50-69 years group. In the 60-69 years group, aging poses a greater risk of lung injury compared to smoking.

Effect of quercetin on granulosa cells development from hierarchical follicles in chicken.

1. The bioflavonoid quercetin is a biologically active component, but its functional regulation of granulosa cells (GCs) during chicken follicular development is little studied. To investigate the effect of quercetin on follicular development in laying hens, an in vitro study was conducted on granulosa cells from hierarchical follicles treated with quercetin.2. The effect of quercetin on cell activity, proliferation and apoptosis of granulosa cells was detected by CCK-8, EdU and apoptosis assays. The effect on progesterone secretion from granulosa cells was investigated by enzyme-linked immunosorbent assay (ELISA). Expression of proliferating cell nuclear antigen (PCNA) mRNA and oestrogen receptors (ERs), as well as the expression of steroid acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA during progesterone synthesis, were measured by real-time quantitative polymerase chain reaction (RT-qPCR). PCNA, StAR and CYP11A1 protein expression levels were detected using Western blotting (WB).3. The results showed that treatment with quercetin in granulosa cells significantly enhanced cell vitality and proliferation, reduced apoptosis and promoted the expression of gene and protein levels of PCNA. The levels of progesterone secretion increased significantly following quercetin treatment, as did the expression levels of StAR and CYP11A1 using the Western Blot (WB) method.4. The mRNA expression levels of ERα were significantly upregulated in the 100 ng/ml and 1000 ng/ml quercetin-treated groups, while there was no significant difference in expression levels of ERß mRNA.

The Association between Dietary Protein Diversity and Protein Patterns with Frailty in Older Chinese Adults: A Population-Based Cohort Study.

OBJECTIVES: Frailty is a pervasive condition among older people worldwide. Despite the association between higher protein intake and lower frailty risk has been well documented, older individuals encounter barriers to enhancing their protein consumption due to reduced appetite and impaired digestive capacity. This study aims to delve into the potential correlation between dietary protein diversity, protein patterns, and the risk of frailty among older Chinese individuals. DESIGN: Prospective cohort study. SETTING: Community-based. PARTICIPANTS: 2,216 participants aged 65 and above and not frail at the baseline were recruited from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset spanning from 2014 to 2018. MEASUREMENTS: Dietary protein diversity was evaluated utilizing a protein diversity score (PDS), calculated based on the results of a food frequency questionnaire. Dietary protein patterns were identified by employing principal component analysis (PCA). Frailty was ascertained using a 40-item frailty index (FI) where FI > 0.21 indicated frailty. Logistic analysis was employed to investigate the association between dietary variables and frailty. RESULTS: 541 participants were identified as frail after a 4-year follow-up. After adjusting for confounders, each 1-unit increase in PDS was linked to a 10% decrease in frailty risk. Compared to individuals with PDS ≤ 1, those with PDS scores of 2-3, 4-5, and 6 had lower risks of frailty, with OR (95% CI) of 0.78 (0.58-1.06), 0.58 (0.38-0.87), 0.42 (0.20-0.81), respectively (P trend = 0.038). Individuals who consistently maintained high PDS demonstrated a lower frailty risk in contrast to those who maintained low PDS (OR = 0.60, 95% CI, 0.41-0.87). Additionally, the "meat-fish" pattern exhibited a protective association with frailty, with OR Q4 versus Q1 (95% CI) of 0.54 (0.40-0.74), P trend < 0.001. CONCLUSION: Maintaining a variety of dietary protein sources and following a "meat-fish" protein pattern might decrease the likelihood of frailty among the older Chinese population.

[Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases].

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

[Best evidence summary of prevention strategies for pressure injury in adult hospitalized burn patients].

Objective: To summarize the best evidence of prevention strategies for pressure injury in adult hospitalized burn patients. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve the published evidence of prevention strategies for pressure injury in adult hospitalized burn patients in the official websites of relevant academic organizations such as International Society for Burn injury, American Burn Association, and Japanese Dermatology Association, National Pressure Injury Advisory Panel, European Pressure Injury Advisory Panel, Pan Pacific Pressure Injury Alliance International Guidelines Website, foreign language databases such as UpToDate, BMJ Best Practice, MedSci, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Web of Science, Embase, and PubMed, and Chinese databases such as China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, and China Clinical Guidelines Library. The literature types include clinical decision-making, evidence summary, guidelines, systematic review, and expert consensus. The search time was till February 21st, 2023. Two researchers independently screened the literature and evaluated the quality, and other researchers extracted and graded the evidence according to the topic. Results: A total of 10 papers were included, including 6 evidence summaries, 3 guidelines, and 1 expert consensus, all with high literature quality. After extracting evidence and classifying, 27 pieces of best evidences were summarized from three aspects, including prevention training and supervision, risk assessment, and prevention measures of pressure injury. Conclusions: A total of 27 pieces of best evidences of prevention strategies for pressure injury in adult hospitalized burn patients were summarized from 3 aspects. Medical workers can follow the best evidence and give personalized prevention strategies according to the specific condition of adult hospitalized burn patients to reduce the incidence of pressure injury.

[A case of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures caused by PHF21A gene variation and review of literature].

Objective: To discuss the clinical and genetic features of intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS). Methods: The clinical and genetic records of a patient who was diagnosed with IDDBCS caused by PHF21A gene variation at Children's Hospital Capital Institute of Pediatrics in 2021 were collected retrospectively. Using " PHF21A gene" as the keyword, relevant articles were searched at CNKI, Wanfang Data and PubMed from establishment of databases to February 2023. Clinical and genetic features of IDDBCS were summarized in the combination of this case. Results: An 8 months of age boy showed overgrowth (height, weight and head circumference were all higher than the 97th percentile of children of the same age and sex) and language and motor developmental delay after birth, and gradually showed autism-like symptoms like stereotyped behavior and poor eye contact. At 8 months of age, he began to show epileptic seizures, which were in the form of a series of spastic seizures with no reaction to adrenocorticotropic hormone but a good response to vigabatrin. Physical examination showed special craniofacial appearances including a prominent high forehead, sparse eyebrows, broad nasal bridge, and downturned mouth with a tent-shaped upper lip. The patient also manifested hypotonia. Whole exome sequencing showed a de novo heterogeneous variant, PHF21A (NM_001101802.1): c.54+1G>A, and IDDBCS was diagnosed. A total of 6 articles (all English articles) were collected, involving this case and other 14 patients of IDDBCS caused by PHF21A gene variation. Clinical manifestations were intellectual disability or developmental delay (15 patients), craniofacial anomalies (15 patients), behavioral abnormalities (12 patients), seizures (9 patients), and overgrowth (8 patients). The main pathogenic variations were frameshift variations (8 patients). Conclusions: IDDBCS should be considered when patients show nervous developmental abnormalities, craniofacial anomalies, seizures and overgrowth. PHF21A gene variation detection helps to make a definite diagnosis.

[A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review].

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

[Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells].

Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.

[HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation].

OBJECTIVE: To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells. METHODS: Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting. RESULTS: The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P < 0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P < 0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 µg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P < 0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P < 0.05), and HSDL2 silencing produced the opposite effects (P < 0.05). CONCLUSION: The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.