Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant.

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

Validation of an established TW3 artificial intelligence bone age assessment system: a prospective, multicenter, confirmatory study.

Background: In 2020, our center established a Tanner-Whitehouse 3 (TW3) artificial intelligence (AI) system using a convolutional neural network (CNN), which was built upon 9059 radiographs. However, the system, upon which our study is based, lacked a gold standard for comparison and had not undergone thorough evaluation in different working environments. Methods: To further verify the applicability of the AI system in clinical bone age assessment (BAA) and to enhance the accuracy and homogeneity of BAA, a prospective multi-center validation was conducted. This study utilized 744 left-hand radiographs of patients, ranging from 1 to 20 years of age, with 378 boys and 366 girls. These radiographs were obtained from nine different children's hospitals between August and December 2020. The BAAs were performed using the TW3 AI system and were also reviewed by experienced reviewers. Bone age accuracy within 1 year, root mean square error (RMSE), and mean absolute error (MAE) were statistically calculated to evaluate the accuracy. Kappa test and Bland-Altman (B-A) plot were conducted to measure the diagnostic consistency. Results: The system exhibited a high level of performance, producing results that closely aligned with those of the reviewers. It achieved a RMSE of 0.52 years and an accuracy of 94.55% for the radius, ulna, and short bones series. When assessing the carpal series of bones, the system achieved a RMSE of 0.85 years and an accuracy of 80.38%. Overall, the system displayed satisfactory accuracy and RMSE, particularly in patients over 7 years old. The system excelled in evaluating the carpal bone age of patients aged 1-6. Both the Kappa test and B-A plot demonstrated substantial consistency between the system and the reviewers, although the model encountered challenges in consistently distinguishing specific bones, such as the capitate. Furthermore, the system's performance proved acceptable across different genders and age groups, as well as radiography instruments. Conclusions: In this multi-center validation, the system showcased its potential to enhance the efficiency and consistency of healthy delivery, ultimately resulting in improved patient outcomes and reduced healthcare costs.

Integrated bioinformatics analysis of noncoding RNAs with tumor immune microenvironment in gastric cancer.

In recent years, molecular and genetic research hotspots of gastric cancer have been investigated, including microRNAs, long noncoding RNAs (lncRNAs) and messenger RNA (mRNAs). The study on the role of lncRNAs may help to develop personalized treatment and identify potential prognostic biomarkers in gastric cancer. The RNA-seq and miRNA-seq data of gastric cancer were downloaded from the TCGA database. Differential analysis of RNA expression between gastric cancer samples and normal samples was performed using the edgeR package. The ceRNA regulatory network was visualized using Cytoscape. KEGG pathway analysis of mRNAs in the ceRNA network was performed using the clusterProfiler package. CIBERSORT was used to distinguish 22 immune cell types and the prognosis-related genes and immune cells were determined using Kaplan-Meier and Cox proportional hazard analyses. To estimate these nomograms, we used receiver operating characteristic and calibration curve studies. The ceRNA regulation network of gastric cancer was built in this study, and the genes in the network were analyzed for prognosis. A total of 980 lncRNAs were differentially expressed, of which 774 were upregulated and 206 were downregulated. A survival study identified 15 genes associated with gastric cancer prognosis, including VCAN-AS1, SERPINE1, AL139002.1, LINC00326, AC018781.1, C15orf54, hsa-miR-145. Monocytes and Neutrophils were associated with the survival rate of gastric cancer. Our research uncovers new ceRNA network for the detection, treatment, and monitoring of gastric cancer.

Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing-site variant and a missense variant in the ROBO3 gene.

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene. RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10-4 , by a review of our in-house database. CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy.

Reproductive outcomes of women with moderate to severe intrauterine adhesions after transcervical resection of adhesion: A systematic review and meta-analysis.

BACKGROUND: Intrauterine adhesions (IUA) refers to the adhesion of the inner wall of the uterus, resulting in complete or partial occlusion of the uterine cavity, which causes a series of symptoms. Transcervical resection of adhesion (TCRA) is the standard surgical method for patients with IUA. However, the recurrence rate of women with moderate to severe IUA is high and it has raised a big concern about the reproductive outcomes. METHODS: We conducted a scoping review by using 4 databases, including Google Scholar, PubMed, Scopus, Embase, and web of science, to retrieve relevant literature from September 1, 2001, to February 1, 2023, and to explore the reproductive outcomes in women with moderate to severe IUA after TCRA treatment. Following defined guidelines, data extraction was carried out by 2 researchers, and the findings were examined by 2 senior academics. The papers were evaluated by 2 reviewers using the inclusion and exclusion criteria. Using a form developed especially for this study, pertinent information was retrieved, including the first author, research design, study duration, age, intervention measurement, pregnancy rate, techniques of conception, and live birth rate. Two researchers conducted a quality assessment to determine any potential bias using the Cochrane technique and the Newcastle-Ottawa scale. RevMan 5.4.1 (The Cochrane Collaboration, London, United Kingdom) was used for data analysis, while I2 was used to evaluate heterogeneity. RESULTS: In total, this study included 2099 participants. After a detailed systematic review and meta-analyses, the results showed that pregnancy and live birth rates were increased significantly after TCRA, and the risk difference of the pregnancy rate was 1.75 [1.17, 2.62]. Besides, in 2 retrospective studies, the risk difference of live birth rate was 2.26, with a 95% confidence interval of 1.99 to 2.58. Moreover, the menstrual status of women also was improved, and the risk difference of hypermenorrhoea and amenorrhea were -0.28 [-0.37, -0.19] and -0.06 [0.26, 0.13], respectively. CONCLUSIONS: Taken together, TCRA is the useful strategy for the treatment of moderate to severe IUA to enhance the reproductive outcomes in women.

Reference intervals for erythrocyte parameters and hemoglobin electrophoresis parameters for young children in Guangxi.

BACKGROUND: Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas. METHODS: 95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28-A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut-off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia. RESULTS: All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above .4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below .4. The optimal cut-off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%-3.2%, 2.5%-3.6% and 2.6%-3.6%, respectively. CONCLUSION: In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases.

Gonadal Y-chromosome mosaicism with 45, X Turner syndrome complicated with bilateral HCG-secreting gonadoblastoma.

We report a rare case of bilateral HCG-secreting gonadoblastomas (Gb) in a 5.25-year-old girl of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism. The clinical data were summarized, and the literatures were reviewed. The patient had enlarged breasts for 2 years and 3 months, with elevated ß-HCG of blood found for 8 months. The level of ß-HCG of cerebrospinal fluid, cranial MRI, chest and abdominal CT, and pelvic MRI were normal. After surgical gonad exploration, biopsy and excision, gonad venous blood hormone examination and SRY gene detection of gonad tissue, the diagnosis was confirmed as HCG-secreting Gb (bilateral) and TS (45, X) with gonad Y chromosome mosaicism. The patient received 4 courses of chemotherapy, and regular outpatient follow-up. At 9 months after gonadectomy, there was no clinical, laboratory, or radiological evidence of recurrence. We reported a nonclassical case of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism, who presented with breast development as the first manifestation and then virilization due to bilateral HCG-secreting gonadoblastomas. Detection of serum ß-HCG and AFP is requisite for the diagnosis of precocious puberty, karyotyping is important for virilizing phenotypic female, and virilization in Turner syndrome implies the existence of Y chromosome(substance) (peripheral blood or tissue mosaicism) and the occurrence of gonadal tumors.

Heterogeneity of the COVID-19 epidemic: what can we learn from it?

OBJECTIVES: The goal of this article is to evaluate and explain the heterogeneity of the Coronavirus disease 2019 (COVID-19) epidemic in Australia, to offer advice for stopping the current outbreak and preparing for a suitable response to epidemics in the future. METHODS: We conducted a review to analyze the epidemic and explain its variable manifestation across states in Australia. Most COVID-19 cases and deaths were in the states of Victoria and New South Wales due to differences in the governance of the epidemic and public health responses (quarantine and contact tracing) among states. RESULTS: Countries could learn from Australia's overall successful response not only through good governance, effective community participation, adequate public health, adequate health system capacity and multisectoral actions but also from the heterogeneity of the epidemic among states. CONCLUSIONS: A successful response to epidemics in countries with a decentralized administration requires multilevel governance with alignment and harmonization of the response.

Targeting CSC-related transcription factors by E3 ubiquitin ligases for cancer therapy.

Evidence has revealed that transcription factors play essential roles in regulation of multiple cellular processes, including cell proliferation, metastasis, EMT, cancer stem cells and chemoresistance. Dysregulated expression levels of transcription factors contribute to tumorigenesis and malignant progression. The expression of transcription factors is tightly governed by several signaling pathways, noncoding RNAs and E3 ubiquitin ligases. Cancer stem cells (CSCs) have been validated in regulation of tumor metastasis, reoccurrence and chemoresistance in human cancer. Transcription factors have been verified to participate in regulation of CSC formation, including Oct4, SOX2, KLF4, c-Myc, Nanog, GATA, SALL4, Bmi-1, OLIG2, POU3F2 and FOX proteins. In this review article, we will describe the critical role of CSC-related transcription factors. We will further discuss which E3 ligases regulate the degradation of these CSC-related transcription factors and their underlying mechanisms. We also mentioned the functions and mechanisms of EMT-associated transcription factors such as ZEB1, ZEB2, Snail, Slug, Twist1 and Twist2. Furthermore, we highlight the therapeutic potential via targeting E3 ubiquitin ligases for modulation of these transcription factors.

Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation.

BACKGROUND: Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL. OBJECTIVES: To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas. METHODS: We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL. RESULTS: Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas. CONCLUSION: The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. The main methods of treating pancreatic cancer are surgery and chemotherapy, but the treatment efficacy is low with a poor prognosis. Immunotherapy represented by PD-1/PD-L1 has brought a milestone progress in the treatment of pancreatic cancer. However, the unique tumor microenvironment of pancreatic cancer presents challenges for immunotherapy. In addition, m6A is a common RNA modification and a potential molecular target in tumor therapy. The expression pattern of m6A in pancreatic cancer is still unclear. LncRNAs also play an essential role in pancreatic cancer development and treatment. In this study, we found that some m6A regulators were significantly elevated in pancreatic cancer and associated with the expression of PD-1/PD-L1. Moreover, we observed that METTL3 can increase the expression of PD-L1. Notably, METTL3 positively regulates the expression of lncRNA MALAT1 in pancreatic cancer cells. Strikingly, lncRNA MALAT1 increased the expression of PD-L1 in pancreatic cancer cells. This finding indicated that METTL3 regulated the expression of PD-L1 possibly via targeting lncRNA MALAT1 in pancreatic cancer cells. Lastly, MALAT1 governed the viability of pancreatic cancer cells. Taken together, lncRNA MALAT1 is involved in METTL3-mediated promotion of PD-L1 expression in pancreatic cancer.

The mechanisms of immune response and evasion by the main SARS-CoV-2 variants.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. SARS-CoV-2 carries a unique group of mutations, and the transmission of the virus has led to the emergence of other mutants such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2) and Omicron (B.1.1.529). The advent of a vaccine has raised hopes of ending the pandemic. However, the mutation variants of SARS-CoV-2 have raised concerns about the effectiveness of vaccines because the data showed that the vaccine was less effective against mutation variants compared to the previous variants. Mutation variants could easily mutate the N-segment structure and receptor domain of its spike glycoprotein (S) protein to escape antibody recognition. Therefore, it is vital to understand the potential immune response and evasion mechanism of SARS-CoV-2 variants. In this review, immune response and evasion mechanisms of several SARS-CoV-2 variants are described, which could provide some helpful advice for future vaccines.

Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer.

Gastric cancer is the fourth most frequent cancer and has a high death rate. Immunotherapy represented by PD-1 has brought hope for the treatment of advanced gastric cancer. Methylation of the m6A genes is linked to the onset and progression of numerous cancers, but there are few studies on gastric cancer. The main purpose of this study aims to analyze the relationship between m6A RNA methylation regulators, PD-L1, prognosis and tumor immune microenvironment (TIME) in gastric cancer. The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases were used to acquire transcriptomic data and clinical information from gastric cancer patients. The changes in m6A regulator expression levels in gastric cancer tissues and normal tissues were studied. Consensus clustering analysis was used to separate gastric cancer samples into two categories. We employed Least Absolute Shrinkage, Selection Operator (LASSO) Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and cBioPortal to analyze the m6A regulators, PD-L1 and TIME in gastric cancer. In gastric cancer tissues, the majority of m6A regulatory factors are considerably overexpressed. Two gastric cancer subgroups (Cluster1/2) based on consensus clustering of 21 m6A regulators. PD-L1 and PD-1 expression levels were significantly higher in gastric cancer tissues, and they were significantly linked with METTL3, WTAP, HNRNPD, ZC3H7B, METTL14, FTO, PCIF1, HNRNPC, YTHDF1 and YTDHF2. Cluster1 showed a large increase in resting memory CD4+ T cells, regulatory T cells, naïve B cells, active NK cells, and resting Mast cells. Cluster1 and Cluster2 were shown to be involved in numerous critical signaling pathways, including base excision repair, cell cycle, nucleotide excision repair, RNA degradation, and spliceosome pathways. Gastric cancer RiskScores based on prognostic factors have been found as independent prognostic indicators. The amount of tumor-infiltrating immune cells is dynamically affected by changes in the copy number of m6A methylation regulators associated with TIME.

The effectiveness of diet intervention in improving the metabolism of overweight and obese women: a systematic review and meta-analysis.

OBJECTIVES: Dietary therapy may improve glucose and lipid metabolism function in women. However, there is no systematic review to investigate the association between metabolic effects and different dietary interventions in obese women. The main purpose of this study is to summarize the current literature and investigate whether different dietary interventions have an effect on glucose and metabolic indicators of overweight or obese women. METHODS: We conducted a scoping review of randomized controlled trial (RCT) studies from 1991 to 2022 by adopting a systematic review and meta-analysis. The database includes Google Scholar, PubMed, Embase and Web of Science. Literature screening, data extraction, and quality assessment were independently completed by 2 researchers. Meta-analysis was performed with RevMan. RESULTS: Twelve articles were extracted and the meta-analysis results showed that the mean difference of metabolic indexes of obese women before and after dietary intervention, including fasting glucose, fasting insulin, HOMA-IR (Homeostasis model assessment-insulin resistance), TG (triglyceride), TC (total cholesterol), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol) are -0.13 [-0.15, -0.10], -2.41 [-3.44, -1.38], -0.13 [-0.15, -0.10], -21.71 [-24.19, -19.22], -21.71 [-24.19, -19.22], -13.29 [-17.86, -8.72], 3.31 [2.22, 4.40], respectively. CONCLUSIONS: Different dietary interventions benefit glucose and lipid metabolism of overweight or obese women. Further study is needed to determine which specific dietary effects have the greatest effect on improving metabolic indicators.

Sink Strength Promoting Remobilization of Non-Structural Carbohydrates by Activating Sugar Signaling in Rice Stem during Grain Filling.

The remobilization of non-structural carbohydrates (NSCs) in the stem is essential for rice grain filling so as to improve grain yield. We conducted a two-year field experiment to deeply investigate their relationship. Two large-panicle rice varieties with similar spikelet size, CJ03 and W1844, were used to conduct two treatments (removing-spikelet group and control group). Compared to CJ03, W1844 had higher 1000-grain weight, especially for the grain growth of inferior spikelets (IS) after removing the spikelet. These results were mainly ascribed to the stronger sink strength of W1844 than that of CJ03 contrasting in the same group. The remobilization efficiency of NSC in the stem decreased significantly after removing the spikelet for both CJ03 and W1844, and the level of sugar signaling in the T6P-SnRK1 pathway was also significantly changed. However, W1844 outperformed CJ03 in terms of the efficiency of carbon reserve remobilization under the same treatments. More precisely, there was a significant difference during the early grain-filling stage in terms of the conversion of sucrose and starch. Interestingly, the sugar signaling of the T6P and SnRK1 pathways also represented an obvious change. Hence, sugar signaling may be promoted by sink strength to remobilize the NSCs of the rice stem during grain filling to further advance crop yield.

Pleomorphism of the HPG axis with NR0B1 gene mutation - a case report of longitudinal follow-up of a proband with central precocious puberty.

OBJECTIVES: X-linked adrenal hypoplasia congenita (AHC) is characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Herein, we report a rare case of X-linked AHC with central precocious puberty (CPP). CASE PRESENTATION: An 11-month-old male patient was found to have premature pubarche, enlargement of the penis, and frequent erection. LH and FSH levels after the GnRHa test were in the pubertal range. Direct sequencing revealed a heterozygous variant of the NR0B1 gene. The proband was treated with hydrocortisone and 9-alpha fludrocortisone because of the significantly elevated ACTH and renin activity. The secondary sexual characteristics relieved gradually. The serum testosterone and LH subsequently returned to the prepubertal range. The basal serum FSH values have been between 1.0 and 2.0 IU/L since the age of 2.25 years, with extremely low AMH levels beginning at 3 years. CONCLUSIONS: The clinical course of CPP with NR0B1 variant may be temporary. HPG axis status of X-linked AHC may probably be pleomorphic during the longitudinal follow-up.

The role of lncRNA OIP5-AS1 in cancer development and progression.

OIP5-AS1, a conserved lncRNA, has been reported to be involved in several biological and pathological processes, including oncogenesis. OIP5-AS1 exerts its oncogenic or antitumor functions via regulation of different miRNAs in various cancer types. In this review, we describe the dysregulation of OIP5-AS1 expression in a variety of human cancers. Moreover, we discuss the multiple functions of OIP5-AS1 in cancer, including in proliferation, apoptosis, autophagy, ferroptosis, cell cycle, migration, metastasis, invasion, epithelial to mesenchymal transition, angiogenesis, cancer stem cells and drug resistance. Furthermore, we provide a future perspective for OIP5-AS1 research. We conclude that targeting OIP5-AS1 might be a promising cancer therapy approach.

Optimised expression and purification of RBP4 and preparation of anti-RBP4 monoclonal antibody.

The expression level of retinol-binding protein 4 (RBP4) protein is closely related to liver damage and plays an important role in the diagnosis and prognosis of cancer. However, the preparation of anti-RBP4 mAb or exploration on the application of anti-RBP4 mAb has not been reported thus far. In the present study, we constructed a pET30a-RBP4 recombinant vector, used E. coli BL21 (DE3) as the vector to express the RBP4 recombinant protein and prepared anti-RBP4 mAb using hybridoma technology. We performed immunohistochemical analysis on hepatocellular carcinoma (HCC) and adjacent tissues by using this anti-RBP4 mAb. In addition to the high-purity RBP4 recombinant protein, we successfully developed the anti-RBP4 mAb with high affinity and specificity; it binds to natural RBP4 protein and is suitable for immunohistochemical analysis.

Study on the Effect and Application Value of Heat-Inactivated Serum on the Detection of Thyroid Function, Tumor Markers, and Cytokines During the SARS-CoV-2 Pandemic.

Purpose: The current explored the impact of heat inactivation of blood samples on the results of a particular clinical test and its potential application value during the SARS-CoV-2 pandemic. We have aimed at providing a reference for clinical testing methods during the pandemic. Methods: Blood samples were selected from our department's routine clinical examination between January 2021 and June 2021. The levels of these samples for quantitative detection of these indicators in each group (n = 90 cases/group) covered normal reference ranges and medically determined levels. For qualitative testing of the indicators, the specimens were additionally classified as negative, weakly positive, and positive (n = 20 cases/group). The specimens were then inactivated, and the differences in relevant indicators before and after inactivation were evaluated. Results: A statistically significant difference was evident between the levels of TSH, T3, FT4, FT3, AFP, NSE, CYFRA211, IRI, IL-1ß, IL-6, IL-8, IL-10, IL-2R, and TNF-α in the non-inactivated group 1 and the inactivated group 1 (P < 0.05). Among them, there was a strong correlation between TSH, T3, FT4, FT3, CYFRA211, IRI, IL-1ß, IL-6, IL-8, and IL-2R levels in the two groups (P < 0.05), however, there was no correlation between AFP (P = 0.256) and NSE (P = 0.352) levels between the two groups (P > 0.05). The detected values of low-level AFP (<4 ng/mL), IL-10, and TNF-α after inactivation were all lower than the detection limit. There was not any statistically significant difference in the levels of tumor markers, such as CEA, CA125, CA724, CA199, CA153, and the quantitative levels of T4, Vit. D, HCG, CPS, and five items of hepatitis B virus (P > 0.05). The positive rate of anti-nuclear antibodies after inactivation was not statistically different from the ones observed before inactivation (P > 0.05). Upon correction by the regression equation, the observed levels of TSH, T3, FT4, FT3, CYFRA211, IRI, IL-1ß, IL-6, IL-8, and IL-2R were not significantly different from those before inactivation (P > 0.05). Conclusion: The heat inactivation of blood samples had different various effects on different test indicators, and some indicators could be corrected by employing regression equations. This detection method could potentially be employed during the SARS-CoV-2 pandemic, thereby effectively preventing iatrogenic infections.

Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human peripheral blood mononuclear cell (PBMC) RNA-Seq data in COVID-19 patients. We found that genes with APA were enriched in innate immunity -related gene ontology categories such as neutrophil activation, regulation of the MAPK cascade and cytokine production, response to interferon-gamma and the innate immune response. We also reported genome-wide AS events and enriched viral transcription-related categories upon SARS-CoV-2 infection. Interestingly, we found that APA events may give better predictions than AS in COVID-19 patients, suggesting that APA could act as a potential therapeutic target and novel biomarker in those patients. Our study is the first to annotate genes with APA and AS in COVID-19 patients and highlights the roles of APA variation in SARS-CoV-2 infection.