Early detection and stratification of colorectal cancer using plasma cell-free DNA fragmentomic profiling.

Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.

Clinicopathological features of papillary thyroid carcinoma in HIV-infected patients.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with an increasing incidence over the last decades. Human immunodeficiency virus (HIV)-induced immune deficiency was one of risk factors for cancer tumorigenesis and development. The aim of this study was to describe the clinicopathological features of PTC in HIV-infected patients and discuss possible connections between PTC and HIV infection. Methods: A total of 17670 patients from September 2009 to April 2022 who underwent PTC surgery for the first time were analyzed retrospectively. At last, 10 patients of PTC with HIV infection (HIV-positive group) and 40 patients without HIV infection (HIV-negative group) were included. The differences in general data and clinicopathological characteristics between the HIV-positive group and the HIV-negative group were analyzed. Results: There were statistically significant differences in age and gender between the HIV-positive group and the HIV-negative group (P<0.05), and males and <55 years old accounted for a higher proportion in the HIV-positive group. The differences in tumor diameter and capsular invasion between the HIV-positive group and HIV-negative group were statistically significant (P<0.05). Meanwhile, in terms of extrathyroid extension (ETE), lymph node metastasis and distant metastasis, the HIV-positive group were significantly higher than the HIV-negative group (P<0.001). Conclusion: HIV infection was a risk factor for larger tumors, more severe ETE, more lymph node metastasis, and more distant metastasis. HIV infection could promote PTC proliferation and make PTC more aggressive. Many factors such as tumor immune escape, secondary infection, etc. may are responsible for these effects. More attention and more thorough treatment should be paid to these patients.

Detection and monitoring of HBV-related hepatocellular carcinoma from plasma cfDNA fragmentation profiles.

Most hepatocellular carcinomas (HCCs) are associated with hepatitis B virus infection (HBV) in China. Early detection of HCC can significantly improve prognosis but is not yet fully clinically feasible. This study aims to develop methods for detecting HCC and studying the carcinogenesis of HBV using plasma cell-free DNA (cfDNA) whole-genome sequencing (WGS) data. Low coverage WGS was performed for 452 participants, including healthy individuals, hepatitis B patients, cirrhosis patients, and HCC patients. Then the sequencing data were processed using various machine learning models based on cfDNA fragmentation profiles for cancer detection. Our best model achieved a sensitivity of 87.10% and a specificity of 88.37%, and it showed an increased sensitivity with higher BCLC stages of HCC. Overall, this study proves the potential of a non-invasive assay based on cfDNA fragmentation profiles for the detection and prognosis of HCC and provides preliminary data on the carcinogenic mechanism of HBV.

Clinical diagnosis and treatment of primary thyroid tuberculosis: a retrospective study

ABSTRACT BACKGROUND: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination. OBJECTIVE: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis. DESIGN AND SETTING: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China). METHODS: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease. RESULTS: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy. CONCLUSION: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Clinical diagnosis and treatment of primary thyroid tuberculosis: a retrospective study.

BACKGROUND: Primary thyroid tuberculosis (PTT) is an uncommon type of extrapulmonary tuberculosis, which is caused by Mycobacterium tuberculosis. It does not have specific clinical manifestations, and most cases are diagnosed through postoperative histopathological examination. OBJECTIVE: To evaluate the diagnostic pattern and management strategy among patients with primary thyroid tuberculosis. DESIGN AND SETTING: Retrospective study on patients with primary thyroid tuberculosis in the First Hospital of Jilin University (Changchun, China). METHODS: Between March 2015 and June 2020, nine cases of PTT were diagnosed and treated in the Department of Thyroid Surgery of the First Hospital of Jilin University. Age at diagnosis, primary symptoms, preoperative biopsy, operation method, pathological classification, acid-fast staining test, anti-TB therapy and prognosis were registered in order to explore the appropriate protocol for diagnosis and treatment of this disease. RESULTS: None of the patients was diagnosed with thyroid tuberculosis before surgery. All the patients underwent surgery. Granulomatous changes or caseous necrosis in thyroid tissue were found through postoperative histopathological evaluation. Polymerase chain reaction (PCR) results for Mycobacterium tuberculosis were positive in all patients. Most patients had a good prognosis after surgery and anti-tuberculosis drug therapy. CONCLUSION: PTT is a rare disease. It is important to improve the preoperative diagnosis. Preoperative diagnostic accuracy relies on increased awareness of the disease and appropriate use of preoperative diagnostic methods, such as PCR detection, fine-needle aspiration cytology, acid-fast bacillus culture, ultrasound and blood sedimentation. PCR detection of M. tuberculosis is recommended as the gold standard for diagnosis.

Value of Defecography in the Diagnostic and Therapeutic Management of the Modified Wells Procedure for Rectal Prolapse.

The main aim of this study was to explore the role of defecography in the preoperative diagnosis and postoperative evaluation of rectal prolapse surgery (modified Wells procedure). We collected and summarized the X-ray performance and then analyzed the results of 107 patients with defecatory dysfunction who underwent defecography from January 2020 to March 2021. Furthermore, the preoperative and 6-month postoperative defecography results and clinical symptoms of 25 patients who underwent rectal prolapse surgery (modified Wells procedure) were compared. Results showed that among the 107 patients with defecation dysfunction, women had worse defecography results than men (P < 0.01). A total of 25 patients successfully completed the surgery without complications such as infection and intestinal fistula and there was no recurrence at 12 months of follow-up. Compared with the preoperative results, anorectal angle during defecation, the depth of rectocele, and perineal descent were significantly improved after the surgery (P < 0.01). Moreover, the patient's feeling of obstructed defecation and incomplete defecation was significantly relieved compared to that before the procedure (P < 0.01). In conclusion, defecography can be used to diagnose rectal prolapse preoperatively and evaluate the surgical effect combined with clinical symptoms postoperatively, which provides a clinical reference.

Multiple endocrine neoplasia type 1 combined with thyroid neoplasm: A case report and review of literatures.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumor syndrome inherited in an autosomal dominant manner and presents mostly as parathyroid, endocrine pancreas (such as gastrinoma) and anterior pituitary tumors. At present, papillary thyroid carcinoma (PTC) and nodular goiter are not regarded as components of MEN1. CASE SUMMARY: A 35-year-old woman presented with MEN1 accompanied by coinstantaneous PTC and nodular goiter. The pathological diagnosis was PTC with cervical lymph node metastasis, nodular goiter, parathyroid cyst and adenomatoid hyperplasia. Genetic testing was performed and a MEN1 gene mutation was detected. The patient underwent unilateral lobectomy of the thyroid gland and surgical removal of the parathyroid tumors. At 18 mo of follow-up, ultrasonic examination of the neck showed no abnormality. Serum calcium and parathyroid hormone levels were normal. No new MEN1-associated tumors were detected. CONCLUSION: The role of inactivating mutations of MEN1 gene in tumorigenesis of PTC and/or nodular goiter remains to be determined by more case reports and further research.

Inhibition of microRNA-130b Alleviated Podocyte Injury Induced by Puromycin Aminonucleoside in vitro.

OBJECTIVE: To investigate the effect of microRNA-130b (miR-130b) on podocyte injury induced by puromycin aminonucleoside (PAN) and its possible mechanisms. METHODS: The immortalized podocytes (HPC) were treated by 25, 50, or 100 µg/mL PAN, then real-time polymerase chain reaction (PCR) was used to detect the expression of miR-130b. The HPC were transfected with miR-130b inhibitor or normal control (NC) inhibitor, and then the cells were stimulated with 100 µg/mL PAN for 24h. Western blot was used to detect the protein expression of synaptopodin and nephrin. Phalloidin dying was used to detect the changes in the cytoskeleton. Flow cytometry was used to measure podocyte apoptosis. Luciferase reporter gene assays were performed to explore the interaction between miR-130b and PGC1α. RESULTS: PAN significantly upregulated the expression of miR-130b. The western blot showed that inhibition of miR-130b increased the protein expression of synaptopodin and nephrin compared to the negative control inhibitor group. The phalloidin dying showed that inhibition of miR-130b alleviated cytoskeletal remodeling of podocytes induced by PAN. Flow-cytometric analysis showed that apoptosis was decreased after miR-130b silencing. The miR-130b mimic could significantly down-regulate the protein expression of PGC1α, and the dual luciferase reporter assay showed that miR-130b induced a decrease in PGC1α 3'-UTR luciferase activity compared to the control mimic group, but there was no significant difference between the control mimic group and the mut·PGC1α 3'-UTR group. CONCLUSION: miR-130b ameliorates podocyte injury induced by PAN through inhibiting the expression of PGC1α.

Expression and clinical significance of B cell translocation gene 2 in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is widely known as a highly fatal cancer, and thus it is important to identify tumor-specific and radiosensitivity-specific markers in ESCC. B cell translocation gene 2 (BTG2) has been considered a novel tumor suppressor gene or radiotherapy sensitivity-associated gene. However, the relationship between BTG2 and ESCC development and radiotherapy sensitivity is uncertain. The present study aims to explore the expression and clinical significance of B cell translocation gene 2 (BTG2) in ESCC by analyzing the RNAseq data from the TCGA and immunohistochemical staining of ESCC samples. We found that the level of BTG2 mRNA was significantly decreased in ESCC patients, and further decreased significantly in radiotherapy resistant patients compared to sensitive patients. The positive expression rate of BTG2 protein was 56.0% (103/184) in 184 ESCC tissue samples and 84.0% (42/50) in normal esophageal mucosal samples, respectively. The positive ratios of BTG2 expression in radiotherapy-sensitive group and radiotherapy resistant group were 57.9% (22/38) and 23.5% (4/17), respectively. Furthermore, the analysis indicates that the expression level of BTG2 significantly correlated with lymph node metastasis and clinical staging in ESCC patients. A multivariate analysis with Cox regression model showed that BTG2 level was an independent risk factor affecting the prognosis of ESCC patients. Above all, the downregulation of BTG2 may be used as a molecular marker to identify and predict ESCC progression and radiosensitivity.

Bacterial and fungal assemblages and functions associated with biofilms differ between diverse types of plastic debris in a freshwater system.

Once in aquatic ecosystems, plastics can be easily colonized by diverse microbes, and these microbial communities on plastics-the 'plastisphere'-often differ from the communities in the surrounding water and other substrates. However, our knowledge of plastic-associated bacterial and fungal communities on diverse plastics in freshwater is poor, especially for fungal communities. Furthermore, intraspecies interactions among bacterial and fungal communities colonized on diverse plastics are poorly known. Here, we characterized the taxonomic composition and diversity of bacteria and fungi on three types of plastics in a lab-scale incubator with freshwater from an urban river. High-throughput sequencing revealed that the alpha diversity of bacterial communities was higher on polyethylene microplastics (MPs) than on polyethylene (PE) and polypropylene (PP) sheets. The structure of bacterial communities on MPs differed from those on plastic sheets. In contrast, no striking differences in alpha diversity and taxonomic composition were observed for fungal communities on different types of plastics. Members of Ascomycota, Basidiomycota, Blastocladiomycota and Mucoromycota dominated fungal assemblages on plastics. Co-occurrence network analysis revealed that the biotic interactions between bacteria and fungi on MPs were less complex than those on PE and PP sheets. The three types of plastics shared no keystone taxa. The functional profiles (KEGG) predicted by Tax4Fun showed that the pathways of alanine, aspartate, glutamate and biotin metabolism were enriched in biofilms on MPs. Nonetheless, the higher complexity of plastic sheet-associated biofilms might make them more resistant to environmental perturbation and facilitate the maintenance of microbial activities.

Schistosoma japonicum Infection Promotes the Response of Tfh Cells Through Down-Regulation of Caspase-3-Mediating Apoptosis.

CD4+ T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in granulomatous responses to Schistosoma japonicum (S. japonicum) infection. However, the role and underlying mechanisms of Tfh cell aggregation in S. japonicum infection remain incompletely understood. In this study, we provide evidence that S. japonicum infection enhances the accumulation of Tfh cells in the spleen, lymph nodes, and peripheral blood of C57BL/6 mice. Infection-induced Tfh cells exhibited more potent effects directly on B cell responses than the control Tfh cells (P < 0.05). Furthermore, reduced apoptosis of Tfh cells was found both in S. japonicum infected mice and in soluble egg antigen (SEA) treated Tfh cells (P < 0.05). Mechanistic studies reveal that caspase-3 is the primary drivers of down-regulated apoptotic Tfh cell death in S. japonicum infection. In summary, this study demonstrates that Tfh cell accumulation might have an impact on the generation of immune responses in S. japonicum infection, and caspase-3 signaling mediated apoptosis down-regulation might responsible for the accumulation of Tfh cell in this course.

YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway.

BACKGROUND: Y-box-binding protein-1 (YB-1) is aberrantly expressed in a variety of cancers. However, the biological functional role of YB-1 in glioma is not yet clear. METHODS: The expression of MDM2 and YB-1 was analyzed by real time PCR. Overexpression and knockdown of YB-1 in glioma cells were created by transfection of pcDNA-YB-1 and siRNA against YB-1, respectively. Cell viability was performed by CCK8 assay. RESULTS: Our findings showed that glioma tissues had higher expressions of YB-1 than that in cancer-free tissues in 54 glioma patients, which were also positively correlated with Murine MDM2 expression. Overexpression of YB-1 or MDM2 renders a drug resistance feature in glioma cell exposed to temozolomide (TMZ), by directly targeting p53. Genetic or chemical inhibition of MDM2 significantly blocked YB-1-modulated response of glioma cells to TMZ. Moreover, inhibition of YB-1 or MDM2 reduced glioma cells metastasis and mortality in mice. CONCLUSION: YB-1 facilitates the resistance of glioma cells to TMZ by direct activation of MDM2/p53 signaling and represents a promising molecular target for glioma treatment.