Pan-cancer identified ARPC1B as a promising target for tumor immunotherapy and prognostic biomarker, particularly in READ.

ARPC1B encodes the protein known as actin-related protein 2/3 complex subunit 1 B (ARPC1B), which controls actin polymerization in the human body. Although ARPC1B has been linked to several human malignancies, its function in these cancers remains unclear. TCGA, GTEx, CCLE, Xena, CellMiner, TISIDB, and molecular signature databases were used to analyze ARPC1B expression in cancers. Visualization of data was primarily achieved using R language, version 4.0. Nineteen tumors exhibited high levels of ARPC1B expression, which were associated with different tumor stages and significantly affected the prognosis of various cancers. The level of ARPC1B expression substantially connected the narrative of ARPC1B expression with several TMB cancers and showed significant changes in MSI. Additionally, tolerance to numerous anticancer medications has been linked to high ARPC1B gene expression. Using Gene Set Variation Analysis/Gene Set Enrichment Analysisanalysis and concentrating on Rectum adenocarcinoma (READ), we thoroughly examined the molecular processes of the ARPC1B gene in pan-cancer. Using WGCNA, we examined the co-expression network of READ and ARPC1B. Meanwhile, ten specimens were selected for immunohistochemical examination, which showed high expression of ARPC1B in READ. Human pan-cancer samples show higher ARPC1B expression than healthy tissues. In many malignancies, particularly READ, ARPC1B overexpression is associated with immune cell infiltration and a poor prognosis. These results imply that the molecular biomarker ARPC1B may be used to assess the prognosis and immune infiltration of patients with READ.

[Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome].

OBJECTIVE: To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). METHODS: The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. RESULTS: The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. CONCLUSION: The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

Characterization and mitigation of artifacts derived from NGS library preparation due to structure-specific sequences in the human genome.

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

A comprehensive performance evaluation, comparison, and integration of computational methods for detecting and estimating cross-contamination of human samples in cancer next-generation sequencing analysis.

Cross-sample contamination is one of the major issues in next-generation sequencing (NGS)-based molecular assays. This type of contamination, even at very low levels, can significantly impact the results of an analysis, especially in the detection of somatic alterations in tumor samples. Several contamination identification tools have been developed and implemented as a crucial quality-control step in the routine NGS bioinformatic pipeline. However, no study has been published to comprehensively and systematically investigate, evaluate, and compare these computational methods in the cancer NGS analysis. In this study, we comprehensively investigated nine state-of-the-art computational methods for detecting cross-sample contamination. To explore their application in cancer NGS analysis, we further compared the performance of five representative tools by qualitative and quantitative analyses using in silico and simulated experimental NGS data. The results showed that Conpair achieved the best performance for identifying contamination and predicting the level of contamination in solid tumors NGS analysis. Moreover, based on Conpair, we developed a Python script, Contamination Source Predictor (ConSPr), to identify the source of contamination. We anticipate that this comprehensive survey and the proposed tool for predicting the source of contamination will assist researchers in selecting appropriate cross-contamination detection tools in cancer NGS analysis and inspire the development of computational methods for detecting sample cross-contamination and identifying its source in the future.

CT and MRI presentation of nasopharyngeal tuberculosis (with a case report).

Nasopharyngeal tuberculosis is a rare extrapulmonary tuberculosis caused by Mycobacterium tuberculosis invading the nasopharynx. Early clinical symptoms are atypical, making the condition easy to overlook and misdiagnosed. We retrospectively reviewed the case of a 37-year-old man who visited the clinic in March 2023, presenting with enlarged cervical lymph nodes persisting for over a year. Computed tomography and magnetic resonance imaging showed the nasopharynx wall was thickened, and cervical multiple enlarged lymph nodes were visible, presenting bead-like appearance. The enhanced scan revealed the lesion uneven enhancement. He was diagnosed with nasopharyngeal carcinoma with lymph node metastasis based on the images. However, the histopathological examination finally confirmed that the nasopharyngeal and neck mass were tuberculous granulomas. Nasopharyngeal tuberculosis is easily misdiagnosed and mistreated, and it is especially difficult to differentiate from nasopharyngeal carcinoma. When diagnosing and treating neck masses, clinicians should consider the possibility of nasopharyngeal tuberculosis in patients with chronic nasopharyngeal symptoms. Nasopharyngoscope biopsy and histopathological examination have great value in the diagnosis of nasopharyngeal tuberculosis.

A case report of Immunoglobulin-G4-related hypertrophic sclerosing pachymeningitis.

IgG4-related diseases (IgG4-RD) are a group of chronic progressive autoimmune diseases of unknown etiology that are increasingly recognized as an important pathophysiological basis for a variety of systemic diseases. It is thought to involve almost any organ of the body, but the involvement of the central nervous system is relatively rare. We report the case of a 56-year-old male patient admitted to the hospital d recurrent dizziness and nausea for more than 3 months. The preoperative imaging was misdiagnosed as a meningioma, with this lesion demonstrated localized inhomogeneous thickening of the meninges in the left parietal region on T2-weighted and T2 fat suppression sequences with localized nodular changes. The patient's final pathologic diagnosis was IgG4-associated sclerosing thick encephalitis. The diagnosis of IgG4-associated hypertrophic pontine meningitis is challenging. Clinically, IgG4-associated sclerosing diseases usually present as mass-like lesions, which can be easily misdiagnosed as neoplastic lesions due to their similar appearance. These fundamentally recognized autoimmune disorders respond well to corticosteroid therapy. Therefore, accurate detection of IgG4-related disease is critical to prevent patients from undergoing unnecessary surgery.

The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer.

Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.

Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche.

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs in vivo was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (<1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro. This study provided the methodology for niche-directed nanotherapeutics development.

Risk assessment scales to predict risk of lower extremity deep vein thrombosis among multiple trauma patients: a prospective cohort study.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication in orthopedic patients. Previous studies have focused on major orthopedic surgery.There are few studies with multiple trauma. We aimed to describe the prevalence of DVT and compare the predictive power of the different risk assessment scales in patients with multiple trauma. METHODS: This prospective cohort study involved multiple trauma patients admitted to our hospital between October 2021 and December 2022. Data were prospectively collected for thrombotic risk assessments using the Risk Assessment Profile for thromboembolism(RAPT), the DVT risk assessment score (DRAS), and the Trauma Embolic Scoring System (TESS), respectively. The receiver operation characteristic (ROC) curve and the area under the curve (AUC) were evaluated to compare the predictive power. The whole leg duplex ultrasound of both lower extremities Doppler ultrasound was used to determine DVT incidence. RESULTS: A total of 210 patients were included, and the incidence of DVT was 26.19%. Distal DVT accounted for 87.27%; postoperative DVT, 72.73%; and bilateral lower extremity thrombosis, 30.91%. There were significant differences in age, education degree, pelvic fracture, surgery, ISS, D-dimer level, length of hospital stay and ICU stay between the thrombosis group and the non-thrombosis group. The AUCs for RAPT, DRAS, and TESS were 0.737, 0.710, and 0.683, respectively. There were no significant differences between the three ROC curves. CONCLUSIONS: The incidence of DVT was relatively high during hospitalization. We prospectively validated the tests to predict risk of DVT among patients with multiple trauma to help trauma surgeons in the clinical administration of DVT prophylaxis.

A unified DNA- and RNA-based NGS strategy for the analysis of multiple types of variants at the dual nucleic acid level in solid tumors.

BACKGROUND: Targeted next-generation sequencing (NGS) is a powerful and suitable approach to comprehensively identify multiple types of variants in tumors. RNA-based NGS is increasingly playing an important role in precision oncology. Both parallel and sequential DNA- and RNA-based approaches are expensive, burdensome, and have long turnaround times, which can be impractical in clinical practice. A streamlined, unified DNA- and RNA-based NGS approach is urgently needed in clinical practice. METHODS: A DNA/RNA co-hybrid capture sequencing (DRCC-Seq) approach was designed to capture pre-capture DNA and RNA libraries in a single tube and convert them into one NGS library. The performance of the DRCC-Seq approach was evaluated by a panel of reference standards and clinical samples. RESULTS: The average depth, DNA data ratio, capture ratio, and target coverage 250 (×) of the DNA panel data had a negative correlation with an increase in the proportion of RNA probes. The SNVs, indels, fusions, and MSI status were not affected by the proportion of RNA probes, but the copy numbers of the target genes were higher than expected in the standard materials, and many unexpected gene amplifications were found using D:R (1:2) and D:R (1:4) probe panels. The optimal ratio of DNA and RNA probes in the combined probe panel was 1:1 using the DRCC-Seq approach. The DRCC-Seq approach was feasible and reliable for detecting multiple types of variants in reference standards and real-world clinical samples. CONCLUSIONS: The DRCC-Seq approach is more cost-effective, with a shorter turnaround time and lower labor requirements than either parallel or sequential targeted DNA NGS and RNA NGS. It is feasible to identify multiple genetic variations at the DNA and RNA levels simultaneously in clinical practice.

Association of infraclavicular axillary vein diameter and collapsibility index with general anesthesia-induced hypotension in elderly patients undergoing gastrointestinal surgery: an observational study.

BACKGROUND: The collapse index of inferior Vena Cava (IVC) and its diameter are important predictive tools for fluid responsiveness in patients, especially critically ones. The collapsibility of infraclavicular axillary vein (AXV) can be used as an alternative to the collapsibility of IVC (IVC-CI) to assess the patient's blood volume. METHODS: A total of 188 elderly patients aged between 65 and 85 years were recruited for gastrointestinal surgery under general anesthesia. Ultrasound measurements AXV and IVC were performed before induction of general anesthesia. Patients were grouped in accordance to the hypotension after induction. ROC curves were used to analyze the predictive value of ultrasound measurements of AXV and IVC for hypotension after induction of anesthesia. Pearson linear correlation was used to assess the correlation of ultrasound measurements and decrease in mean arterial blood pressure (MAP). RESULTS: The maximum diameter of AXV(dAXVmax) and the maximum diameter of IVC (dIVCmax) were not related to the percentage decrease in MAP; the collapsibility of AXV (AXV-CI) and IVC-CI were positively correlated with MAP changes (correlation coefficients:0.475, 0.577, respectively, p < 0.001). The areas under the curve (AUC) was 0.824 (0.759-0.889) for AXV-CI, and 0.874 (0.820-0.928) for IVC-CI. The optimal threshold for AXV-CI was 31.25% (sensitivity 71.7%, specificity 90.1%), while for IVC-CI was 36.60% (sensitivity 85.9%, specificity 79.0%). Hypotension and down-regulation of MAP during induction can be accurately predicted by AXV-Cl after correction for confounding variables. CONCLUSION: Infraclavicular axillary vein diameter has no significant correlation with postanesthesia hypotension, whereas AXV-CI may predict postanesthesia hypotension during gastrointestinal surgery of the elderly. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of China on 05/06/2022 (ChiCTR2200060596).

Ultrasensitive Bio-H2S Gas Sensor Based on Cu2O-MWCNT Heterostructures.

Developing a respiratory analysis disease diagnosis platform for the H2S biomarker has great significance for the real-time detection of various diseases. However, achieving highly sensitive and rapid detection of H2S gas at the parts per billion level at low temperatures is one of the most critical challenges for developing portable exhaled gas sensors. Herein, Cu2O-multiwalled carbon nanotube (MWCNT) heterostructures with excellent gas sensitivity to H2S at room temperature and a lower temperature were successfully synthesized by a facile two-dimensional (2D) electrodeposition in situ assembly method. The combination of Cu2O and MWCNTs via the principle of optimal conductance growth not only reduced the initial resistance of the material but also provided an ideal interfacial barrier structure. Compared to the response of the pure Cu2O sensor, that of the Cu2O-MWCNT sensor to 1 ppm of H2S increased nearly 800 times at room temperature, and the response time decreased by more than 500 s. In addition to the excellent sensitivity with detection limits as low as 1 ppb, the Cu2O-MWCNT sensor was extremely selective with low-temperature adaptability. The sensor had a response value of 80.6 to 0.1 ppm of H2S at -10 °C, which is difficult to achieve with sensors based on oxygen adsorption/desorption mechanisms. The sensor was used for the detection of real oral exhaled breath, confirming its feasibility as a real-time disease monitoring sensor. The Cu2O-MWCNT heterostructures maximized the advantages of the individual components and laid the experimental foundation for future applications of highly sensitive portable breath analysis platforms for monitoring H2S.

[Clinical Characteristics and Prognostic Factors of Patients with Primary Parotid Gland Lymphoma].

OBJECTIVE: To explore the clinical characteristics and prognostic factors of patients with primary parotid gland lymphoma, and construct a prognostic model nomogram for patients with primary diffuse large B-cell lymphoma (DLBCL) of parotid gland. METHODS: Primary parotid gland lymphoma and primary DLBCL of parotid gland patients from 1984 to 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis were conducted to determine the independent prognostic factors of primary parotid gland lymphoma and primary DLBCL of parotid gland, respectively. According to the established independent prognostic factors of primary DLBCL of parotid gland, nomogram was built to predict 3- and 5-year survival, and the discrimination and calibration of the model were evaluated by concordance index (C-index) and calibration plots. RESULTS: A total of 2 610 patients with primary parotid gland lymphoma were identified. Their median age was 66(15-99) years old, the male to female ratio was 1∶1.8, and 20.5% of them was primary DLBCL of parotid gland, which was the most common histological subtype in aggressive lymphomas. Multivariate Cox regression analysis showed that sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma, while age, marital status, surgery, and chemotherapy were the independent prognostic factors of primary DLBCL of parotid gland. The C-index of the prediction model was 0.702(95%CI: 0.696-0.768), reflecting a good discrimination ability. The predicted value probability of the calibration plots was close to the actual value probability, reflecting a good accuracy ability. CONCLUSIONS: Sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma. The nomogram survival prediction model for primary DLBCL of parotid gland patients can assist clinical decision effectively.

Dietary Plant Polysaccharides for Cancer Prevention: Role of Immune Cells and Gut Microbiota, Challenges and Perspectives.

Dietary plant polysaccharides, one of the main sources of natural polysaccharides, possess significant cancer prevention activity and potential development value in the food and medicine fields. The anti-tumor mechanisms of plant polysaccharides are mainly elaborated from three perspectives: enhancing immunoregulation, inhibiting tumor cell growth and inhibiting tumor cell invasion and metastasis. The immune system plays a key role in cancer progression, and immunomodulation is considered a significant pathway for cancer prevention or treatment. Although much progress has been made in revealing the relationship between the cancer prevention activity of polysaccharides and immunoregulation, huge challenges are still met in the research and development of polysaccharides. Results suggest that certain polysaccharide types and glycosidic linkage forms significantly affect the biological activity of polysaccharides in immunoregulation. At present, the in vitro anti-tumor effects and immunoregulation of dietary polysaccharides are widely reported in articles; however, the anti-tumor effects and in vivo immunoregulation of dietary polysaccharides are still deserving of further investigation. In this paper, aspects of the mechanisms behind dietary polysaccharides' cancer prevention activity achieved through immunoregulation, the role of immune cells in cancer progression, the role of the mediatory relationship between the gut microbiota and dietary polysaccharides in immunoregulation and cancer prevention are systematically summarized, with the aim of encouraging future research on the use of dietary polysaccharides for cancer prevention.

Clinical significance of plasma PD-L1+ exosomes in the management of diffuse large B cell lymphoma.

PD-L1+ exosome have been reported to be a promising prognostic biomarker in various cancers. However, its clinical value in diffuse large B cell lymphoma (DLBCL) has not been defined yet. In this study, a total of 165 plasma samples from 78 patients with DLBCL undergoing standard first-line R-CHOP regimens were collected at three different time points (pretreatment, and after 3 and 6 cycles of R-CHOP) to determine the proportions of PD-L1+ exosomes by flow cytometry. We found that high pretreatment plasma PD-L1+ exosome correlated with indicators of poor clinical outcome that included high Ki-67 expression (P = 0.02), double expressor lymphoma (P = 0.005), immunohistochemical PD-L1+ tumor tissue (P = 0.006), and the baseline maximal standardized uptake values (P = 0.0003). Pretreatment plasma PD-L1+ exosome was an independent factor by multivariate analysis with logistic regression (P = 0.0301). Moreover, the pretreatment PD-L1+ exosome was a strong predictor of final treatment responses of either CR or non-CR by ROC analysis (P < 0.001). PD-L1+ exosome level declined significantly in patients who experienced CR (pretreatment vs. after 3 cycles/after 6 cycles, P < 0.05), but not in the non-CR group. Intriguingly, plasma PD-L1+ exosome after 3 cycles (AUC = 0.857; 95%CI: 0.728-0.939) might represent a more sensitive indicator than radiographic assessment after 3 cycles (AUC = 0.626; 95%CI: 0.477-0.758) for evaluating the therapeutic response of DLBCL patients (P = 0.0136). Our results suggest that plasma PD-L1+ exosomes may represent a new biomarker for the dynamic monitoring of treatment response.

Sex-specific disparities of serum pepsinogen I in relation to body mass index.

OBJECTIVES: The clinical significance of serum pepsinogen (PG) for screening gastric cancer has been a controversial topic. Serum PG I levels have been demonstrated to be correlated with age, sex, and the Helicobacter pylori (HP) infection. However, the underlying factors that influence serum PG I variations remain to be fully elucidated. We aimed to evaluate the impacts of sex and body mass index (BMI) on PG I in Chinese population. METHODS: The cross-sectional study recruited 4,299 apparently healthy participants in Fujian Province. Serum PG levels were automatically measured using ELISA method. Serum H. pylori-IgG antibody was detected by the colloidal gold immunoassay. Clinical characteristics were obtained by questionnaire. RESULTS: Totally, 2,263 participants who had tests of serum PG and anti-HP IgG antibody were enrolled. Increased BMI and serum uric acid were observed in males with low PG I value (<70 µg/L). Multiple logistic regression showed the presence of overweight was the independent risk factor for male participants with low PG I level (odds ratio [OR] 1.519; p=0.017). However, the association was not found in females. CONCLUSIONS: Sex-specific association of serum low PG I with overweight was observed in the southeast coastal areas of China. Thus, effects of sexual dimorphism should not be ignored during the clinical utilization of serum PG I.

High expression of miR-107 and miR-17 predicts poor prognosis and guides treatment selection in acute myeloid leukemia.

Background: The prognostic significance of miR-107 and miR-17 in patients with acute myeloid leukemia (AML) remains unclear. Methods: A total of 173 patients with de novo AML from the Cancer Genome Atlas database were enrolled in this study and further divided into a chemotherapy group (98 cases) and an allogeneic hematopoietic stem cell transplantation (allo-HSCT) group (75 cases) according to their therapy regimen. Results: In the chemotherapy cohort, high miR-107 or miR-17 expression was associated with poorer overall survival (OS) and event-free survival (EFS). On the other hand, there were no significant differences in OS and EFS between the high- and low-expression subgroups in the allo-HSCT group. Next, we stratified the total number of patients with AML into high- and low-expression groups according to the median expression levels of miR-107 or miR-17. In the high miR-107 or miR-17 expression group, patients treated with allo-HSCT had longer OS than those treated with chemotherapy. In the low miR-107 or miR-17 expression group, no significant differences in OS and EFS were observed between the two therapy subgroups. When patients were further clustered into three groups (both low miR-107 and low miR-17, either high miR-107 or high miR-17, and both high miR-107 and high miR-17), patients with both high miR-107 and high miR-17 expression had the worst OS and EFS of the entire group and of the chemotherapy group. On the other hand, there were no significant differences in OS and EFS among the three subgroups in the allo-HSCT group. Cox regression confirmed the concurrence of high expression of miR-107 and miR-17 might act as an independent prognostic factor for EFS and OS in the entire group and the chemotherapy group. Bioinformatics analysis showed differentially expressed genes (DEGs) associated with miR-107 and miR-17 expression were mainly enriched in multiple metabolic processes. Conclusions: The combination of miR-107 and miR-17 provides prognostic significance for patients with AML and should be considered in the clinical selection of the optimal treatment regimen when deciding between chemotherapy and allo-HSCT.

Sequential application of copy number variation sequencing and quantitative fluorescence polymerase chain reaction in genetic analysis of miscarriage and stillbirth.

BACKGROUND: Copy number variation sequencing (CNV-seq) could detect most chromosomal abnormalities except polyploidy, and quantitative fluorescence polymerase chain reaction (QF-PCR) is a supplementary method to CNV-seq in triploid detection. This study aimed to evaluate the feasibility of sequential application of CNV-seq and QF-PCR in genetic analysis of miscarriage and stillbirth. METHODS: A total of 261 fetal specimens were analyzed by CNV-seq, and QF-PCR was only further performed for samples with normal female karyotype identified by CNV-seq. Cost and turnaround time (TAT) was analyzed for sequential detection strategy. Subgroup analysis and logistic regression were carried out to evaluate the relationship between clinical characteristics (maternal age, gestational age, and number of pregnancy losses) and the occurrence of chromosomal abnormalities. RESULTS: Abnormal results were obtained in 120 of 261 (45.98%) cases. Aneuploidy was the most common abnormality (37.55%), followed by triploidy (4.98%) and pathogenic copy number variations (pCNVs) (3.45%). CNV-seq could detect the triploidy with male karyotype, and QF-PCR could further identify the remaining triploidy with female karyotype. In this study, we found more male triploidies than female triploidies. With the same ability in chromosomal abnormalities detection, the cost of sequential strategy decreased by 17.35% compared with combined strategy. In subgroup analysis, significant difference was found in the frequency of total chromosomal abnormalities between early abortion group and late abortion group. Results of logistic regression showed a trend that pregnant women with advanced age, first-time abortion, and abortion earlier than 12 weeks were more likely to detect chromosomal aberrations in their products of conception. CONCLUSION: Sequential application of CNV-seq and QF-PCR is an economic and practical strategy to identify chromosomal abnormalities in fetal tissue.

[Effects of Decitabine Combined with Anlotinib on Proliferation and Apoptosis of Multiple Myeloma Cells].

OBJECTIVE: To investigate the biological effects and its relative mechanism of decitabine combined with anlotinib on multiple myeloma cells. METHODS: The human MM cell lines and primary cells were treated with different concentrations of decitabine, anlotinib, and decitabine+anlotinib, respectively. The cell viability was detected and combination effect was calculated by CCK-8 assay. The apoptosis rate was measured by flow cytometry and the level of c-Myc protein was determined by Western blot. RESULTS: Both decitabine and anlotinib could effectively inhibit the proliferation and induce the apoptosis of MM cell lines NCI-H929 and RPMI-8226. The effect of combined treatment on the inhibition of cell proliferation and induction of apoptosis was stronger than that of single-drug treatment. The combination of the two drugs also showed strong cytotoxicity in primary MM cells. Decitabine and anlotinib could down-regulate the level of c-Myc protein in MM cells and the c-Myc level in the combination group was the lowest. CONCLUSION: Decitabine combined with anlotinib can effectively inhibit the proliferation and induce apoptosis of MM cells, which provides a certain experimental basis for the treatment of human MM.

Detecting liquid remnants of solid tumors treated with curative intent: Circulating tumor DNA as a biomarker of minimal residual disease (Review).

Circulating tumor DNA (ctDNA) has emerged as a promising biomarker of minimal residual disease (MRD) in solid tumors. There is increasing evidence to suggest that the detection of ctDNA following curative­intent treatments has high potential in anticipating future relapse in various solid tumors. Multiple liquid biopsy technical approaches and commercial platforms, including tumor­informed and tumor­agnostic ctDNA assays, have been developed for ctDNA­based MRD detection in solid tumors. Accurate ctDNA­based MRD analysis remains a critical technical challenge due to the very low concentration of ctDNA in peripheral blood samples, particularly in cancer patients following a curative­intent surgery or treatment. The present review summarizes the current key technical approaches that can be used to analyze ctDNA in the surveillance of MRD in solid tumors and provides a brief update on current commercial assays or platforms available for ctDNA­based MRD detection. The available evidence to date supporting ctDNA as a biomarker for detection of MRD in various types of solid tumors is also reviewed. In addition, technical and biological variables and considerations in pre­analytical and analytical steps associated with ctDNA­based MRD detection are discussed.