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Human papillomavirus (HPV) infection plays an important role in cervical cancer. HPV is classified within the Papillomaviridae family and is a non-enveloped, small DNA virus. HPV infection can be classified into two distinct scenarios: i) With or without integration into the host chromosomes. Detection of its infection can be useful in the study of cervical lesions. In the present review, the structural and functional features of HPV, HPV typing, infection and transmission mode, the risk factors for cervical susceptibility to infection and HPV detection methods are described in detail. The development of HPV detection methods may have far-reaching significance in the prevention and treatment of cervical disease. This review summarizes the advantages and limitations of each HPV detection method.

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Ovarian cancer is one of the most common gynecologic malignancies. Recurrence and metastasis often occur after treatment, and it has the highest mortality rate of all gynecological tumors. Cancer stem cells (CSCs) are a small population of cells with the ability of self-renewal, multidirectional differentiation, and infinite proliferation. They have been shown to play an important role in tumor growth, metastasis, drug resistance, and angiogenesis. Ovarian cancer side population (SP) cells, a type of CSC, have been shown to play roles in tumor formation, colony formation, xenograft tumor formation, ascites formation, and tumor metastasis. The rapid progression of tumor angiogenesis is necessary for tumor growth; however, many of the mechanisms driving this process are unclear as is the contribution of CSCs. The aim of this review was to document the current state of knowledge of the molecular mechanism of ovarian cancer stem cells (OCSCs) in regulating tumor angiogenesis.

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OBJECTIVE: To explore the genetic etiology of a fetus with short limbs identified by prenatal ultrasonography. METHODS: A fetus detected with short limb malformations at Shengjing Hospital Affiliated to China Medical University on October 25, 2021 was selected as the study subject. Prenatal ultrasound and post-abortion imaging were carried out to determine the phenotypic characteristics of the fetus. Amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected. Following extraction of genomic DNA, whole-exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. Online software was used to predict the structural changes of the mutant proteins. RESULTS: Prenatal ultrasound showed that the fetus had a small bell-shaped thorax, markedly shortened limbs, flat midface, a small nose with anteriorly tilted nostrils, and a small mandible. Post-abortion CT showed typical short and wide fetal ribs, cupped metaphyses at both ends, short long bones with wide metaphyses, resulting in a dumbbell-shaped appearance and curved thoracic vertebrae. Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c.2251G>T and c.3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein. Sanger sequencing confirmed that the variants were respectively inherited from its parents. CONCLUSION: A rare fetus with Fibrochondrogenesis type 1 due to compound heterozygous variants of the COL11A1 gene has been diagnosed. Above finding has enabled genetic counseling and reproductive guidance for this family.

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OBJECTIVE: Uterine corpus endometrial carcinoma (UCEC), a kind of gynecologic malignancy, poses a significant risk to women's health. The precise mechanism underlying the development of UCEC remains elusive. Zinc finger protein 554 (ZNF554), a member of the Krüppel-associated box domain zinc finger protein superfamily, was reported to be dysregulated in various illnesses, including malignant tumors. This study aimed to examine the involvement of ZNF554 in the development of UCEC. METHODS: The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay. Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection. CCK-8, wound healing, and Transwell invasion assays were employed to assess cell proliferation, migration, and invasion. Propidium iodide (PI) staining combined with fluorescence-activated cell sorting (FACS) flow cytometer was utilized to detect cell cycle distribution. qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels. Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5 (RBM5). RESULTS: The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines. Decreased expression of ZNF554 was associated with higher tumor stage, decreased overall survival, and reduced disease-free survival in UCEC. ZNF554 overexpression suppressed cell proliferation, migration, and invasion, while also inducing cell cycle arrest. In contrast, a decrease in ZNF554 expression resulted in the opposite effect. Mechanistically, ZNF554 transcriptionally regulated RBM5, leading to the deactivation of the Wingless (WNT)/ß-catenin signaling pathway. Moreover, the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression on ß-catenin and p-glycogen synthase kinase-3ß (p-GSK-3ß). Similarly, the deliberate activation of RBM5 reduced the increase in ß-catenin and p-GSK-3ß caused by the suppression of ZNF554. In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown. Additionally, when RBM5 was overexpressed, it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels. CONCLUSION: ZNF554 functions as a tumor suppressor in UCEC. Furthermore, ZNF554 regulates UCEC progression through the RBM5/WNT/ß-catenin signaling pathway. ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

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OBJECTIVE: To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type II Cornelia de Lange syndrome (CdLS2). METHODS: A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c.2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG). CONCLUSION: The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.

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Diffuse intrinsic pontine glioma (DIPG) is a highly malignant brain tumor that mainly occurs in children with extremely low overall survival. Traditional therapeutic strategies, such as surgical resection and chemotherapy, are not feasible mostly due to the special location and highly diffused features. Radiotherapy turns out to be the standard treatment method but with limited benefits of overall survival. A broad search for novel and targeted therapies is in the progress of both preclinical investigations and clinical trials. Extracellular vesicles (EVs) emerged as a promising diagnostic and therapeutic candidate due to their distinct biocompatibility, excellent cargo-loading-delivery capacity, high biological barrier penetration efficiency, and ease of modification. The utilization of EVs in various diseases as biomarker diagnoses or therapeutic agents is revolutionizing modern medical research and practice. In this review, we will briefly talk about the research development of DIPG, and present a detailed description of EVs in medical applications, with a discussion on the application of engineered peptides on EVs. The possibility of applying EVs as a diagnostic tool and drug delivery system in DIPG is also discussed.

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Fischer-Tropsch synthesis (FTS), which provides a green route to the production of clean fuels and fine chemicals, represents some significant applications of catalytic materials and processes in the chemical industry. FTS reactions show a diversity of mechanisms, involve various catalytic materials, and offer options for continuous investigation. Cobalt-based catalysts have been widely used for Fischer-Tropsch synthesis both in academia and in industry. This mini-review will focus on relevant research achievements in cobalt-based FTS catalysts by our group in the Dalian Institute of Chemical Physics (DICP). Specific contents will include the development of Co/Co2C-based nano-catalysts (i) for the highly selective synthesis of clean fuels over Co-based catalysts supported by carbon materials and (ii) for the synthesis of linear α-alcohols and olefins over Co-Co2C-based catalysts supported by carbon materials. The direct synthesis of linear α-alcohols from syngas using a Co-Co2C/AC catalyst is highlighted. The innovative work of FTS using activated carbon (AC)-supported Co/Co2C-based nano-catalysts could bring some insight into new FTS catalyst designs.

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Objective: To study the effectiveness and feasibility of cryogenic disinfectants in different cold scenarios and analyze the key points of on-site cryogenic disinfection. Methods: Qingdao and Suifenhe were selected as application sites for the manual or mechanical spraying of cryogenic disinfectants. The same amount of disinfectant (3,000 mg/L) was applied on cold chain food packaging, cold chain containers, transport vehicles, alpine environments, and article surfaces. The killing log value of the cryogenic disinfectant against the indicator microorganisms ( Staphylococcus aureus and Escherichia coli) was used to evaluate the on-site disinfection effect. Results: When using 3,000 mg/L with an action time of 10 min on the ground in alpine regions, the surface of frozen items, cold-chain containers, and cold chain food packaging in supermarkets, all external surfaces were successfully disinfected, with a pass rate of 100%. The disinfection pass rates for cold chain food packaging and cold chain transport vehicles of centralized supervised warehouses and food processing enterprises were 12.5% (15/120), 81.67% (49/60), and 93.33% (14/15), respectively; yet, the surfaces were not fully sprayed. Conclusion: Cryogenic disinfectants are effective in disinfecting alpine environments and the outer packaging of frozen items. The application of cryogenic disinfectants should be regulated to ensure that they cover all surfaces of the disinfected object, thus ensuring effective cryogenic disinfection.

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OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

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The activating molecule in Beclin1-regulated autophagy protein 1 (AMBRA1) is an intrinsically disordered protein that regulates the survival and death of cancer cells by modulating autophagy. Although the roles of autophagy in cancer are controversial and context-dependent, inhibition of autophagy under some circumstances can be a useful strategy for cancer therapy. As AMBRA1 is a pivotal autophagy-associated protein, targeting AMBRA1 similarly may be an underlying strategy for cancer therapy. Emerging evidence indicates that AMBRA1 can also inhibit cancer formation, maintenance, and progression by regulating c-MYC and cyclins, which are frequently deregulated in human cancer cells. Therefore, AMBRA1 is at the crossroad of autophagy, tumorigenesis, proliferation, and cell cycle. In this review, we focus on discussing the mechanisms of AMBRA1 in autophagy, mitophagy, and apoptosis, and particularly the roles of AMBRA1 in tumorigenesis and targeted therapy.

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PURPOSE: Circulating blood plasma derived extracellular vesicles (BEVs) containing proteins hold promise for their use as minimally invasive biomarkers for predicting response to cancer therapy. The main goal of this study was to establish the efficiency and utility of the particle purification liquid chromatography (PPLC) BEV isolation method and evaluate the role of BEVs in predicting breast cancer (BC) patient response to neoadjuvant chemotherapy (NAC). METHODS: PPLC isolation was used to separate BEVs from non-EV contaminants and characterize BEVs from 17 BC patients scheduled to receive NAC. Using LC-MS/MS, we compared the proteome of PPLC-isolated BEVs from patients (n = 7) that achieved a pathological complete response (pCR) after NAC (responders [R]) to patients (n = 10) who did not achieve pCR (non-responders [NR]). Luminal MCF7 and basaloid MDA-MB-231 BC cells were treated with isolated BEVs and evaluated for metabolic activity by MTT assay. RESULTS: NR had elevated BEV concentrations and negative zeta potential (ζ-potential) prior to receipt of NAC. Eight proteins were enriched in BEVs of NR. GP1BA (CD42b), PECAM-1 (CD31), CAPN1, HSPB1 (HSP27), and ANXA5 were validated using western blot. MTT assay revealed BEVs from R and NR patients increased metabolic activity of MCF7 and MDA-MB-231 BC cells and the magnitude was highest in MCF7s treated with NR BEVs. CONCLUSION: PPLC-based EV isolation provides a preanalytical separation process for BEVs devoid of most contaminants. Our findings suggest that PPLC-isolated BEVs and the five associated proteins may be established as predictors of chemoresistance, and thus serve to identify NR to spare them the toxic effects of NAC.

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Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns. Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis. Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects. Conclusion: For the emergency management of anaphylaxis we conclude that: • NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis • Prompt and proper administration of epinephrine is critical.

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Congenital heart disease (CHD) is the most common noninfectious cause of death during the neonatal stage. T-box transcription factor 1 (TBX1) is the main genetic determinant of 22q11.2 deletion syndrome (22q11.2DS), which is a common cause of CHD. Moreover, ferroptosis is a newly discovered kind of programmed cell death. In this study, the interaction among TBX1, miR-193a-3p, and TGF-ß2 was tested using quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and dual-luciferase reporter assays. TBX1 silencing was found to promote TGF-ß2 messenger ribonucleic acid (mRNA) and protein expression by downregulating the miR-193a-3p levels in H9c2 cells. In addition, the TBX1/miR-193a-3p/TGF-ß2 axis was found to promote ferroptosis based on assessments of lipid reactive oxygen species (ROS) levels, Fe2+ concentrations, mitochondrial ROS levels, and malondialdehyde (MDA) contents; Cell Counting Kit-8 (CCK-8) assays and transmission electron microscopy; and Western blotting analysis of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), NADPH oxidase 4 (NOX4), and acyl-CoA synthase long-chain family member 4 (ACSL4) protein expression. The protein expression of NRF2, GPX4, HO-1, NOX4, and ACSL4 and the level of MDA in human CHD specimens were also detected. In addition, TBX1 and miR-193a-3p expression was significantly downregulated and TGF-ß2 levels were high in human embryonic CHD tissues, as indicated by the H9c2 cell experiments. In summary, the TBX1/miR-193a-3p/TGF-ß2 axis mediates CHD by inducing ferroptosis in cardiomyocytes. TGF-ß2 may be a target gene for CHD diagnosis and treatment in children.

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OBJECTIVE: To explore the genetic basis for a child affected with cerebral creatine deficiency syndrome 1 (CCDS1). METHODS: High-throughput sequencing was carried out to screen pathogenic variant associated with the clinical phenotype of the proband. The candidate variant was verified by Sanger sequencing. RESULTS: High-throughput sequencing revealed that the proband has carried heterozygous c.327delG variant of the SLC6A8 gene, which was verified by Sanger sequencing.Neither parent was found to carry the same variant. CONCLUSION: The de novo heterozygous c.327delG variant of the SLC6A8 gene probably underlay the CCDS1 in this child.

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Background: As one of the three malignant genital tumors, mortality in women with ovarian cancer is consistently high worldwide. It is of great importance to find prognostic markers for diagnosis and treatment of ovarian cancer. In this study, the authors utilized the bioinformatics analysis to identify the potential key genes to reveal the potential mechanism for ovarian cancer. Materials and Methods: The authors used the gene expression profile (GSE14407) to perform differentially expressed gene (DEG) analysis and the weighted gene co-expression network analysis. They selected the key module and performed the gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the genes in the hub module. Then they screened the key genes in the hub module, and further validated their expression level. Results: A total of 3124 DEGs were detected after differential gene expression analysis; of these, 433 were upregulated genes and 2691 were downregulated genes. The authors selected the brown module that is significantly associated with the BRCA gene expression. Then they selected 30 hub genes from the protein-protein interaction network. The authors identified the PDZ binding kinase (PBK) as the prognosis-associated hub gene whose expression was significantly high in the ovarian cancer tissue. Conclusions: The bioinformatics analysis for the DEGs could be important to understand the pathogenesis for ovarian cancer. In this study, PBK is identified as a potential marker that might improve the understanding of the molecular mechanism and the diagnosis level for ovarian cancer.

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OBJECTIVE: To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple. METHODS: High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery. RESULTS: The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth. CONCLUSION: For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.

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BACKGROUND: Extracellular vesicles (EVs) are regulators of cell-cell interactions and mediators of horizontal transfer of bioactive molecules between cells. EV-mediated cell-cell interactions play roles in physiological and pathophysiological processes, which maybe modulated by exposure to pathogens and cocaine use. However, the effect of pathogens and cocaine use on EV composition and function are not fully understood. RESULTS: Here, we used systems biology and multi-omics analysis to show that HIV infection (HIV +) and cocaine (COC) use (COC +) promote the release of semen-derived EVs (SEV) with dysregulated extracellular proteome (exProtein), miRNAome (exmiR), and exmiR networks. Integrating SEV proteome and miRNAome revealed a significant decrease in the enrichment of disease-associated, brain-enriched, and HIV-associated miR-128-3p (miR-128) in HIV + COC + SEV with a concomitant increase in miR-128 targets-PEAK1 and RND3/RhoE. Using two-dimensional-substrate single cell haptotaxis, we observed that in the presence of HIV + COC + SEV, contact guidance provided by the extracellular matrix (ECM, collagen type 1) network facilitated far-ranging haptotactic cues that guided monocytes over longer distances. Functionalizing SEV with a miR-128 mimic revealed that the strategic changes in monocyte haptotaxis are in large part the result of SEV-associated miR-128. CONCLUSIONS: We propose that compositionally and functionally distinct HIV + COC + and HIV-COC- SEVs and their exmiR networks may provide cells relevant but divergent haptotactic guidance in the absence of chemotactic cues, under both physiological and pathophysiological conditions.

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OBJECTIVE: To analyze the clinical phenotype and pathogenic variant in a child diagnosed with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH). METHODS: Clinical phenotype of the child was reviewed. Whole exome sequencing was carried out for the child. Candidate variant was verified by Sanger sequencing of the family member. RESULTS: The proband manifested dyskinesia, development delay, cerebellar hypoplasia and bilateral hearing impairment. WES results revealed that the proband has carried a pathogenic c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene, which was verified by Sanger sequencing to be a de novo variant. CONCLUSION: The c.1641_1644delACAA (p.Thr548Trpfs*69) variant of the CASK gene probably underlay the MICPCH in the proband. Above finding has provided a basis for genetic counseling. WES should be considered for the diagnosis of neurological dysplasia.

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OBJECTIVE: To analyze the phenotype and genetic variant of a fetus with dysplasia of cerebellar vermis. METHODS: Gestational status and family history of the gravida was taken in combination with the imaging results of the fetus. Following elected abortion, fetal tissue and peripheral blood samples of the couple were collected for the extraction of genome DNA. Whole exome sequencing was carried out to screen potential variant associated with the phenotype of the proband. Specific PCR primers were designed to verify the results by Sanger sequencing. RESULTS: Prenatal ultrasound revealed that the fetal vermis cerebellum was poorly developed, which was similar to the previous pregnancy. Whole exome sequencing revealed that the fetus has carried compound heterozygous variants of the CPLANE1 gene, namely c.7978C>T and c.7169delT, which were respectively inherited from the husband and wife. CONCLUSION: The c.7978C>T and c.7169delT compound heterozygous variants of the CPLANE1 gene probably underlay the dysplasia of cerebellar vermis in the fetus, which has provided a basis for genetic counseling and prenatal diagnosis.

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