IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53.

Cancer stem cells (CSCs) are considered tumor-initiating cells and the main drivers of disease progression. Targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the up-regulation of IL-13RA2 expression in colorectal cancer (CRC) tissues and spheroid cells. The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC. We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients. Biologically, recombinant IL-13 (rIL-13) stimulation promoted the sphere formation, proliferation, and migration of CRC cells in vitro and enhanced tumorigenesis in vivo. This phenotype could be reversed by knocking down IL-13RA2. Mechanistically, IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs, which was crucial for the biological functions of IL-13. We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein, enhancing the interaction of UBE3C and p53, thereby inducing the K48-linked ubiquitination of p53. In conclusion, the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination, adding an important layer to the connection between IL-13 and p53, which can be translated into novel targeted therapies.

Somatic mutation spectrum of a Chinese cohort of pediatrics with vascular malformations.

BACKGROUND: Somatic mutations of cancer driver genes are found to be responsible for vascular malformations with clinical manifestations ranging from cutaneous birthmarks to life-threatening systemic anomalies. Till now, only a limited number of cases and mutations were reported in Chinese population. The purpose of this study was to describe the somatic mutation spectrum of a cohort of Chinese pediatrics with vascular malformations. METHODS: Pediatrics diagnosed with various vascular malformations were collected between May 2019 and October 2020 from Beijing Children's Hospital. Genomic DNA of skin lesion of each patient was extracted and sequenced by whole-exome sequencing to identify pathogenic somatic mutations. Mutations with variant allele frequency less than 5% were validated by ultra-deep sequencing. RESULTS: A total of 67 pediatrics (33 males, 34 females, age range: 0.1-14.8 years) were analyzed. Exome sequencing identified somatic mutations of corresponding genes in 53 patients, yielding a molecular diagnosis rate of 79.1%. Among 29 PIK3CA mutations, 17 were well-known hotspot p.E542K, p.E545K and p.H1047R/L. Non-hotspot mutations were prevalent in patients with PIK3CA-related overgrowth spectrum, accounting for 50.0% (11/22) of detected mutations. The hotspot GNAQ p.R183Q and TEK p.L914F mutations were responsible for the majority of port-wine stain/Sturge-Weber syndrome and venous malformation, respectively. In addition, we identified a novel AKT1 p.Q79K mutation in Proteus syndrome and MAP3K3 p.E387D mutation in verrucous venous malformation. CONCLUSIONS: The somatic mutation spectrum of vascular malformations in Chinese population is similar to that reported in other populations, but non-hotspot PIK3CA mutations may also be prevalent. Molecular diagnosis may help the clinical diagnosis, treatment and management of these pediatric patients with vascular malformations.

The morphology and spectral characteristics of the compound eye of Agasicleshygrophila (Selman & Vogt, 1971) (Coleoptera, Chrysomelidae, Galerucinae, Alticini).

The first exploratory study was conducted on the compound eye morphology and spectral characteristics of Agasicleshygrophila (Selman & Vogt, 1971) to clarify its eye structure and its spectral sensitivity. Scanning electron microscopy, paraffin sectioning, and transmission electron microscopy revealed that A.hygrophila has apposition compound eyes with both eucones and open rhabdom. The micro-computed tomography (CT) results after 3D reconstruction demonstrated the precise position of the compound eyes in the insect's head and suggested that the visual range was mainly concentrated in the front and on both sides of the head. The electroretinogram (ERG) experiment showed that red, yellow, green, blue, and ultraviolet light could stimulate the compound eyes of A.hygrophila to produce electrical signals. The behavioural experiment results showed that both males and females had the strongest phototaxis to yellow light and positive phototaxis to red, green, and blue light but negative phototaxis to UV light. This study of the compound eyes of A.hygrophila will be helpful for decoding its visual mechanism in future studies.

Construction of double reaction zones for long-life quasi-solid aluminum-ion batteries by realizing maximum electron transfer.

Achieving high energy density and long cycling life simultaneously remains the most critical challenge for aluminum-ion batteries (AIBs), especially for high-capacity conversion-type positive electrodes suffering from shuttle effect in strongly acidic electrolytes. Herein, we develop a layered quasi-solid AIBs system with double reaction zones (DRZs, Zone 1 and Zone 2) to address such issues. Zone 1 is designed to accelerate reaction kinetics by improving wetting ability of quasi-solid electrolyte to active materials. A composite three-dimensional conductive framework (Zone 2) interwoven by gel network for ion conduction and carbon nanotube network as electronic conductor, can fix the active materials dissolved from Zone 1 to allow for continuing electrochemical reactions. Therefore, a maximum electron transfer is realized for the conversion-type mateials in DRZs, and an ultrahigh capacity (400 mAh g-1) and an ultralong cycling life (4000 cycles) are achieved. Such strategy provides a new perspective for constructing high-energy-density and long-life AIBs.

A novel 3D bilayer hydrogel tri-culture system for studying functional motor units.

BACKGROUND: A motor unit (MU) is formed by a single alpha motor neuron (MN) and the muscle fibers it innervates. The MU is essential for all voluntary movements. Functional deficits in the MU result in neuromuscular disorders (NMDs). The pathological mechanisms underlying most NMDs remain poorly understood, in part due to the lack of in vitro models that can comprehensively recapitulate multistage intercellular interactions and physiological function of the MU. RESULTS: We have designed a novel three-dimensional (3D) bilayer hydrogel tri-culture system where architecturally organized MUs can form in vitro. A sequential co-culture procedure using the three cell types of a MU, MN, myoblast, and Schwann cell was designed to construct a co-differentiating tri-culture on a bilayer hydrogel matrix. We utilized a µ-molded hydrogel with an additional Matrigel layer to form the bilayer hydrogel device. The µ-molded hydrogel layer provides the topological cues for myoblast differentiation. The Matrigel layer, with embedded Schwann cells, not only separates the MNs from myoblasts but also provides a proper micro-environment for MU development. The completed model shows key MU features including an organized MU structure, myelinated nerves, aligned myotubes innervated on clustered neuromuscular junctions (NMJs), MN-driven myotube contractions, and increases in cytosolic Ca2+ upon stimulation. CONCLUSIONS: This organized and functional in vitro MU model provides an opportunity to study pathological events involved in NMDs and peripheral neuropathies, and can serve as a platform for physiological and pharmacological studies such as modeling and drug screening. Technically, the rational of this 3D bilayer hydrogel co-culture system exploits multiple distinct properties of hydrogels, facilitating effective and efficient co-culturing of diverse cell types for tissue engineering.

Prognosis after splenectomy plus pericardial devascularization vs transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding.

BACKGROUND: Portal hypertension combined with esophagogastric variceal bleeding (EGVB) is a serious complication in patients with hepatitis B virus (HBV)-related cirrhosis in China. Splenectomy plus pericardial devascularization (SPD) and transjugular intrahepatic portosystemic shunt (TIPS) are effective treatments for EGVB. However, a comparison of the effectiveness and safety of those methods is lacking. AIM: To compare the prognosis after SPD vs TIPS for acute EGVB after failure of endoscopic therapy or secondary prophylaxis of variceal rebleeding (VRB) in patients with HBV-related cirrhosis combined with portal hypertension. METHODS: This retrospective cohort study included 318 patients with HBV-related cirrhosis and EGVB who underwent SPD or TIPS at West China Hospital of Sichuan University during 2009-2013. Propensity score-matched analysis (PSM), the Kaplan-Meier method, and multivariate Cox regression analysis were used to compare overall survival, VRB rate, liver function abnormality rate, and hepatocellular carcinoma (HCC) incidence between the two patient groups. RESULTS: The median age was 45.0 years (n = 318; 226 (71.1%) males). During a median follow-up duration of 43.0 mo, 18 (11.1%) and 33 (21.2%) patients died in the SPD and TIPS groups, respectively. After PSM, SPD was significantly associated with better overall survival (OS) (P = 0.01), lower rates of abnormal liver function (P < 0.001), and a lower incidence of HCC (P = 0.02) than TIPS. The VRB rate did not differ significantly between the two groups (P = 0.09). CONCLUSION: Compared with TIPS, SPD is associated with higher postoperative OS rates, lower rates of abnormal liver function and HCC, and better quality of survival as acute EGVB treatment after failed endoscopic therapy or as secondary prophylaxis of VRB in patients with HBV-related cirrhosis combined with portal hypertension. There is no significant between-group difference in VRB rates.

[Bioinformatics analysis of the association between long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and immune cell infiltration in ovarian serous cystadenocarcinoma].

Objective To investigate the expression of long non-coding RNA ubiquitin-specific peptidase 30 antisense RNA 1 (lncRNA USP30-AS1) and its relationship with immune infiltration in ovarian serous cystadenocarcinoma (OSC), and to determine its prognostic role in OSC. Methods The Cancer Genome Atlas (TCGA) database was utilized to retrieve the expression of USP30-AS1 and clinical information of 384 OSC patients. Wilcoxon rank-sum test was employed to compare the expression of USP30-AS1 between OSC and normal ovarian tissues. Logistic regression analysis was conducted to assess the relationship between clinical pathological features and USP30-AS1. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate enrichment pathways and functions and quantify the degree of immune cell infiltration in USP30-AS1. Based on the expression level of long non-coding RNA (lncRNA) USP30-AS1, the samples were divided into high and low expression groups according to the expression mean. Log-rank tests, univariate and multivariate proportional hazards model (Cox) were used to compare prognostic differences between different USP30-AS1 expression groups. The impact of lncRNA USP30-AS1 expression on other genomic analyses was also analyzed. Results High expression of USP30-AS1 was significantly associated with the International Federation of Gynecology and Obstetrics (FIGO) stage of the tumor. Multivariate survival analysis indicated that USP30-AS1 expression level served as an independent prognostic marker for OSC. GSEA data showed that high expression of USP30-AS1 might activate programmed death 1 (PD-1) signaling pathway, cytotoxic T lymphocyte-associated protein 4 (CTLA4) pathway, B-cell receptor signaling pathway, cell apoptosis, fibroblast growth factor receptor (FGFR) signaling pathway, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. The expression of USP30-AS1 was negatively correlated with immune cell infiltration, including B cells, CD4+ T cells, dendritic cells, CD8+ T cells, and neutrophils. Conclusion USP30-AS1 may be used as a prognostic molecular marker for OSC.

Thyroid Accumulation of 99mTc-DTPA in Graves Disease.

ABSTRACT: 99mTc-DTPA dynamic renal scintigraphy for evaluating glomerular filtration rate was performed in a 29-year-old woman with hyperuricemia and Graves disease. Subsequently, 99mTc-DTPA orbital scintigraphy was conducted to determine the activity of Graves ophthalmopathy. Thyroid accumulation of 99mTc-DTPA was incidentally identified. This should be cautiously distinguished from 99mTc-pertechnetate uptake, considering that the salivary glands, oral cavity, and stomach were not visualized. Our case demonstrates that augmentation of blood supply, enhancement of capillary permeability, and accumulation of inflammatory exudate may be involved in the pathological process of Graves disease.

Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study.

Recent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.

Risk factor analysis of postoperative complications after adjunctive pulmonary resection in patients with multidrug-resistant tuberculosis: A multi-institutional study.

BACKGROUND AND OBJECTIVE: Multidrug-resistant tuberculosis (MDR-TB) requires extended treatment with regimens with multiple side effects, resulting in high treatment failure rates. Adjunctive lung resection combined with anti-tubercular agents improves outcomes. However, few studies have evaluated the potential harm from surgery and determined the optimal conditions for surgery. We aimed to analyze perioperative conditions to assess risk factors for postoperative complications in a multi-institutional setting. METHODS: This retrospective study included 44 patients with MDR-TB who underwent adjunctive lung resection at three management groups of the Taiwan MDR-TB consortium between January 2007 and December 2020. Demographic data, clinical characteristics, radiological findings, sputum culture status before surgery, primary or acquired drug resistance, surgical procedure, complications, and treatment outcomes were collected and analyzed. Multivariate logistic regression was used to identify risk factors for postoperative complications. RESULTS: Twenty-seven patients (61.4%) underwent lung resection using video-assisted thoracic surgery (VATS). The overall surgical complication rate was 20.5%, and the surgical mortality rate was 9.1%. Postsurgical hemothorax was the most common complication (11.4%). According to the univariate analysis, hilum involvement in images, positive preoperative sputum culture, and thoracotomy approach were unfavorable factors. VATS approach [adjusted OR, 0.088 (95% CI, 0.008-0.999)] was the only favorable factor identified by multivariate analysis. CONCLUSION: The minimally invasive approach is a growing trend, and lobectomies and sublobar resections were the main procedures for MDR-TB. The VATS approach significantly reduced the surgical complication rate. Postsurgical hemothorax was noteworthy, and meticulous hemostasis of the chest wall and residual lung surface is critical for successful resections.

Confused subcutaneous nodules in children: Differential diagnosis of pilomatricoma in children.

BACKGROUND: Pilomatricoma is a common but easily misdiagnosed tumor in children. AIMS: To differentiate pilomatricoma from other common subcutaneous nodules in children. PATIENTS/METHODS: Misdiagnosed subcutaneous nodules in four children were recorded. RESULTS: A red mass on a 7-year-old boy's head which had been misdiagnosed pyogenic granuloma was proved to be pilomatricoma. A red mass on an 8-month-old boy's face which had been misdiagnosed infantile hemangioma also turned to be pilomotricoma. A red mass on a 21-month-old girl's breast, which had been misdiagnosed pilomatricoma, was proved to be infantile myofibroma. A subcutaneous nodule under a 13-month-old girl's armpit, which had been misdiagnosed pilomatricoma, turned to be BCG-associated lymphadenitis. CONCLUSIONS: When a child with a subcutaneous nodule attends, pilomatricoma, vascular tumors, fibrous tumors, and BCG-associated lymphadenitis should be considered.

Iodine-125 brachytherapy for a desmoid tumor in the abdomen-thorax: A retrospective study.

PURPOSE: To investigate the safety and efficacy of iodine-125 seed implantation in the treatment of abdomen-thorax desmoid tumors (DTs). METHODS AND MATERIALS: Data from 14 DT patients who received brachytherapy with iodine-125 seeds were retrospectively collected from 2014 to 2020. The operation was completed using CT guidance and the treatment plan system (TPS). The number of lesions and the target dosimetry parameters were recorded. After brachytherapy, the lesions were evaluated using response evaluation criteria in solid tumors (RECIST). RESULTS: Fourteen patients with 18 lesions were enrolled in this study; eleven lesions were in the thorax, seven were in the abdomen, and the lesion gross tumor volume (GTV) was 82.10 cc (interquartile range [IQR]: 40.37, 203.42 cc). The median number of seeds was 88 (IQR: 35, 158), and the median prescription dose was 120 Gy (IQR: 115, 120 Gy). The D90 was 123 ± 16.7 Gy, the V90 was 97% (IQR: 95.00, 97.25%), and the V200 was 27% (IQR: 14.50, 33.00%). The median follow-up time for each lesion was 34 (IQR: 23, 67) months, and the local response rate was 100%. Following brachytherapy, the overall survival was 52.3 ± 30.72 months. One year after brachytherapy, one patient experienced persistent worsening of a brachial plexus injury; another received a ureteral stent. No brachytherapy-related complications were observed in the remaining patients. CONCLUSIONS: Iodine-125 brachytherapy is a novel treatment option for DT of the abdomen and thorax. Although it is a safe and effective treatment, the radiation dose of iodine-125 brachytherapy for DT-embedded organs at risk must be investigated further.

The Effects of Nebulized Inhaled Triptolide on Airway Inflammation in a Mouse Model of Asthma.

Inhalation of nebulized TP has received little attention in the past. Here, we intend to investigate the effect of nebulized inhaled TP on airway inflammation in a mouse model of asthma. 29 SPF BALB/c mice were divided into four groups: blank control (Blk, n = 5), normal saline (NS, n = 8), dexamethasone (Dex, n = 8), and TP (n = 8). During the process of sensitization, mice in the three intervention groups were treated with nebulized NS, an injection of Dex, and nebulized triptolide, respectively. Then bronchoalveolar lavage fluid (BALF), peripheral blood, and lung tissue were collected. Relevant cytokines, transcriptional factors, and CD4+Th17+ T cell proportions were assessed and compared. IL-6, IL-17, IL-23, and TGF-ß1 demonstrated a significant difference between groups in the following order: Dex < TP < NS (P ≤ 0.001), while IL-10 changed in the opposite direction (P < 0.001). At the transcriptional level in lung tissue, the Ct value of IL-17 in the Dex group was significantly higher than in the NS and TP groups (P < 0.001). Meanwhile, it was higher in the TP group than in the NS group (P < 0.001). The Ct value of RORγt demonstrated a significant difference among three groups in the following order: Dex > TP > NS (P < 0.001). An opposite trend of FoxP3 Ct value was revealed in the order: NS > TP > Dex. The proportion of CD4+Th17+ cells was 9.53 ± 2.74% in the NS group, 4.23 ± 2.26% in the Dex group, and 6.76 ± 2.99% in the TP group, which shows significant differences between the NS and Dex (P < 0.001) or NS and TP groups (P < 0.05). Inhalation of nebulized triptolide can play a role in suppressing airway inflammation with inflammatory cytokines and transcriptional factors reduced and CD4+Th17+ T cells dampened, also in a manner less than injected dexamethasone.

Deficits in neuromuscular control of increasing force in patients with chronic lateral epicondylitis.

Objective: This study investigated the neuromuscular control of increasing and releasing force in patients with chronic lateral epicondylitis (CLE). Methods: Fifteen patients with CLE (10 males, 5 females, 46.5 ± 6.3 years) and fifteen healthy participants (9 males, 6 females, 45.3 ± 2.5 years) participated in this study. In addition to power grip and maximal voluntary contraction (MVC) of wrist extension, force fluctuation dynamics and characteristics of inter-spike intervals (ISI) of motor units (MUs) with various recruitment thresholds in the extensor carpi radialis brevis (ECRB) and extensor carpi radialis longus (ECRL) during a designated force-tracking task with a trapezoidal target (0%-75%-0% MVC) were assessed. Results: Besides a smaller MVC of wrist extension, the patients exhibited significantly greater task errors (p = 0.007) and force fluctuations (p = 0.001) during force increment than the healthy counterparts. Nevertheless, no force variables significantly differed between groups during force release (p > 0.05). During force increment, the amplitudes of the motor unit action potential of the ECRB and ECRL muscles of the patients were smaller than those of the heathy counterparts (p < 0.001). The patient group also exhibited a higher percentage of motor units (MU) with lower recruitment threshold (<5% MVC) in the ECRL/ECRB muscles and a lower percentage of MU with higher recruitment threshold (>40% MVC) in the ECRB muscle, compared to the healthy group. During force increment, the patient group exhibited a higher rate of decrease in inter-spike intervals (ISIs) of motor units with lower recruitment thresholds (<10% MVC) in the ECRB and ECRL muscles, compared to the control group (p < 0.005). Conclusion: The patients with CLE exhibited more pronounced impairment in increasing force than in releasing force. This impairment in increasing force is attributed to deficits in tendon structure and degenerative changes in the larger motor units of the wrist extensors. To compensate for the neuromuscular deficits, the rate of progressive increase in discharge rate of the remaining smaller motor units (MUs) is enhanced to generate force. Significance: The deficits in neuromuscular control observed in CLE with degenerative changes cannot be fully explained by the experimental pain model, which predicts pain-related inhibition on low-threshold motor units.

Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction.

BACKGROUND: The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR. METHODS: A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS). RESULTS: No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group. CONCLUSION: Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group. Level of evidence Level III.

[Prenatal diagnosis of two fetuses with Xp22.31 microdeletion syndrome indicated by non-invasive prenatal testing].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT. METHODS: Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation . RESULTS: NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001_7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940_8003247)×0, with a 1.54 Mb deletion in Xp22.31 region. CONCLUSION: NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.

[Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION: NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

TNF+ regulatory T cells regulate the stemness of gastric cancer cells through the IL13/STAT3 pathway.

Regulatory T cells (Tregs) are an important component of the tumor microenvironment; however, the interaction between Tregs and gastric cancer cells is not completely understood. Recent studies have shown that Tregs participate in cancer cell stemness maintenance. In this study, we performed single-cell RNA sequencing of gastric cancer and adjacent tissues and found that Tregs with high TNF expression were recruited to gastric cancer tissues and were significantly correlated with patient survival. TNF+ Tregs significantly contribute to tumor growth and progression. Our studies have further demonstrated that TNF+ Tregs promote the stemness of gastric cancer cells through the IL13/STAT3 pathway. Therefore, blocking the interaction between TNF+ Tregs and gastric cancer cells may be a new approach in the treatment of gastric cancer.