Aberrant expression of thyroidal hormone receptor α exasperating mitochondrial dysfunction induced sarcopenia in aged mice.

Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that the expression of thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting that the alteration of thyroidal elements, especially the decreased TRα, might attenuate local THs action thus to cause the degeneration of SM with aging, while the underlying mechanism remains to be further explored. In this study, decreased expression of myogenic regulators Myf5, MyoD1, mitophagy markers Pink1, LC3II/I, p62, as well as mitochondrial dynamic factors Mfn1 and Opa1, accompanied by increased reactive oxygen species (ROS), showed concomitant changes with reduced TRα expression in aged mice. Further TRα loss- and gain-of-function studies in C2C12 revealed that silencing of TRα not only down-regulated the expression of above-mentioned myogenic regulators, mitophagy markers and mitochondrial dynamic factors, but also led to a significant decrease in mitochondrial activity and maximum respiratory capacity, as well as more mitochondrial ROS and damaged mitochondria. Notedly, overexpression of TRα could up-regulate the expression of those myogenic regulators, mitophagy markers and mitochondrial dynamic factors, meanwhile also led to an increase in mitochondrial activity and number. These results confirmed that TRα could concertedly regulate mitochondrial dynamics, autophagy, and activity, and myogenic regulators rhythmically altered with TRα expression. Summarily, these results suggested that the decline of TRα might cause the degeneration of SM with aging by regulating mitochondrial dynamics, mitophagy and myogenesis.

Single-cell Technologies Provide Novel Insights into Liver Physiology and Pathology.

The liver is the largest glandular organ in the body and has a unique distribution of cells and biomolecules. However, the treatment outcome of end-stage liver disease is extremely poor. Single-cell sequencing is a new advanced and powerful technique for identifying rare cell populations and biomolecules by analyzing the characteristics of gene expression between individual cells. These cells and biomolecules might be used as potential targets for immunotherapy of liver diseases and contribute to the development of precise individualized treatment. Compared to whole-tissue RNA sequencing, single-cell RNA sequencing (scRNA-seq) or other single-cell histological techniques have solved the problem of cell population heterogeneity and characterize molecular changes associated with liver diseases with higher accuracy and resolution. In this review, we comprehensively summarized single-cell approaches including transcriptomic, spatial transcriptomic, immunomic, proteomic, epigenomic, and multiomic technologies, and described their application in liver physiology and pathology. We also discussed advanced techniques and recent studies in the field of single-cell; our review might provide new insights into the pathophysiological mechanisms of the liver to achieve precise and individualized treatment of liver diseases.

Predicting prognosis and immune status in sarcomas by identifying necroptosis-related lncRNAs.

BACKGROUND: Sarcomas are a type of highly heterogeneous malignant tumors originating from mesenchymal tissues. Necroptosis is intricately connected to the oncogenesis and progression of tumors. The main goal of this research is to assess the prognostic value of necroptosis-related lncRNAs (NRlncRNAs) in sarcomas and to develop a risk model based on NRlncRNAs to evaluate prognostic and immune status of the sarcomas. METHODS: We screened NRlncRNAs using the gene co-expression network, developed a prognostic risk model of sarcomas, and then verified the model. Following that, various bioinformatics analysis algorithms were employed to analyze the distinct characteristics of patients of the risk model. Furthermore, the function and regulatory mechanism of NRlncRNA SNHG6 in sarcomas were investigated through osteosarcoma cell experiments, such as qRT-PCR, Western blot, CCK-8, clone formation, and transwell assay. RESULTS: We successfully developed a NRlncRNAs-related prognostic risk model and screened 5 prognosis-related NRlncRNAs, with SNGH6 being the most significant for prognosis of patients. According to results, the significant differences exist in prognosis, clinical characteristics, and tumor immune status among patients of the risk model. The experiments of osteosarcoma cells demonstrated that NRlncRNA SNHG6 knockdown significantly attenuated the cells' proliferation, migration, and invasion. qRT-PCR and WB results showed that SNHG6 regulated AXL and AKT signaling. CONCLUSIONS: We have developed an innovative investigation on NRlncRNAs, which can serve as a reference for diagnosis, therapy, and prognosis of sarcomas. Additionally, we demonstrated that NRlncRNA SNHG6 regulated AXL and AKT signaling in osteosarcoma cells and the proliferation, migration, and invasion of tumor cells.

Pancreatic metastasis of extra-skeletal mesenchymal chondrosarcoma diagnosed by ultrasound endoscopy-guided fine-needle aspiration.

A 47-year-old man with a history of ESMC resection of the left chest wall seven years ago was admitted to our hospital due to mid-upper abdominal pain and jaundice for more than 10 days. Laboratory tests showed elevated direct bilirubin, alanine aminotransferase, gamma-glutamyltranspeptidase, and alkaline phosphatase. Computed tomography (CT) of the abdomen revealed soft tissue mass in the head and body of the pancreas with irregularly shaped calcifications, and an enhanced scan showed heterogeneous enhancement. Combined with the patient's past medical history, the possibility of pancreatic metastasis of ESMC was considered. After anti-inflammatory, hepatoprotective, and cholagogical treatment jaundice improved, and ultrasound endoscopy-guided fine-needle aspiration (EUS-FNA) was performed to clarify the nature of the mass, which showed a 4.1*4.2 cm mixed echogenic area with internal calcification in the head of the pancreas. Aspiration pathology showed proliferation of short spindle and round cells into nests, the immunohistochemistry stain showed CD99 (+); CD34, CD117, Dog-1, and S-100 were negative. Pancreatic metastasis of ESMC was diagnosed. Four months later, endoscopic biliary metal stent drainage (EMBD) was performed when the patient developed obstructive jaundice again due to lesion progression. PET/CT at a 2-year follow-up showed multiple high-density calcifications and abnormally increased FDG metabolism throughout the body.

Bridging polyp in an anastomosis resected by endoscopic submucosal dissection (ESD).

A 60-year-old man was admitted to our hospital for routine postoperative review of colon cancer. He underwent a colonoscopy, which showed a bridge-like polyp located 13 cm from the anal verge, with the base of the polyp located 1.5 cm above the anastomosis and the head of it located on the anastomosis and fusion growth with the anastomosiz. The patient accepted ESD to remove the lesion. During the ESD procedure, the basal of the polyp was incised using an insulated-tip knife, when the polyp tip located at the anastomosis was gradually dissected with a hook knife, severe fibrosis and three staples was found in the submucosal. We carefully separated the scar tissue and pulled out staples with hook knife in electrocision mode. Finally, we removed the lesion completely.

Does Increasing the Bend Angle of a Stylet to 90° Increase the Nasotracheal Intubation Success Rate?

BACKGROUND: Video-stylet-guided nasotracheal intubation (NTI) is an effective technique for airway management. However, the impact of the bend angle on the success rate of intubation remains unclear. PURPOSE: Does increasing the bend angle of a stylet to 90° increase NTI success rate?. STUDY DESIGN, SETTING, SAMPLE: This prospective randomized controlled trial was conducted in the operating room of a population-based hospital. Adult patients requiring NTI were recruited. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable is the choice of stylet bend angle (90° vs 70° bend) in NTI. MAIN OUTCOME VARIABLE(S): The primary outcome variables were success rates of NTI, defined as the proportion of successful intubation cases to total cases. COVARIATES: Demographics, intubation time, the distance from the thyroid prominence to the nostril, additional maneuvers applied during intubation, and cases of epistaxis were recorded. ANALYSES: The student's t-test was used to compare continuous variables between groups. Ordinal data (intubation attempts, head extension, and epistaxis) were analyzed using the Wilcoxon rank-sum test. As appropriate, frequency (external pharyngeal pressure) was analyzed using the χ2 test or Fisher's exact test. A P value of <.05 was considered statistically significant. RESULTS: Of the 103 subjects assessed for eligibility, 98 were enrolled in the study. The mean age (27.0 ± 6.9 years vs 27.0 ± 4.1 years, P = .972) and sex differences (male/female: 9/40 vs 7/42, P = .136) were comparable between groups. The overall success rate in the 70° group was significantly lower than that in the 90° group (91.8 vs 100%, P < .001). The intubation time in the 70° group was significantly longer than that in the 90° group (43.2 ± 15.8 s vs 33.7 ± 7.3 s, P < .001). CONCLUSIONS AND RELEVANCE: A 90° bend angle of the stylet significantly improves the likelihood of successful NTI.

A proteomic study on gastric impairment in rats caused by microcystin-LR.

Microcystins (MCs) are the most common cyanobacterial toxins. Epidemiological investigation showed that exposure to MCs can cause gastro-intestinal symptoms, gastroenteritis and gastric cancer. MCs can also accumulate in and cause histopathological damage to stomach. However, the exact mechanisms by which MCs cause gastric injury were unclear. In this study, Wistar rats were administrated 50, 75 or 100 µg microcystin-LR (MC-LR)/kg, body mass (bm) via tail vein, and histopathology, response of anti-oxidant system and the proteome of gastric tissues at 24 h after exposure were studied. Bleeding of fore-stomach and gastric corpus, inflammation and necrosis in gastric corpus and exfoliation of mucosal epithelial cells in gastric antrum were observed following acute MC-LR exposure. Compared with controls, activities of superoxide dismutase (SOD) were significantly greater in gastric tissues of exposed rats, while activities of catalase (CAT) were less in rats administrated 50 µg MC-LR/kg, bm, and concentrations of glutathione (GSH) and malondialdehyde (MDA) were greater in rats administrated 75 or 100 µg MC-LR/kg, bm. These results indicated that MC-LR could disrupt the anti-oxidant system and cause oxidative stress. The proteomic results revealed that MC-LR could affect expressions of proteins related to cytoskeleton, immune system, gastric functions, and some signaling pathways, including platelet activation, complement and coagulation cascades, and ferroptosis. Quantitative real-time PCR (qRT-PCR) analysis showed that transcriptions of genes for ferroptosis and gastric function were altered, which confirmed results of proteomics. Overall, this study illustrated that MC-LR could induce gastric dysfunction, and ferroptosis might be involved in MC-LR-induced gastric injury. This study provided novel insights into mechanisms of digestive diseases induced by MCs.

Subcellular localization and relevant mechanisms of human cancer-related micropeptides.

Rapid advances in high-quality sequencing and bioinformatics have invalidated the argument that noncoding RNAs (ncRNAs) are junk transcripts that do not encode proteins. Increasing evidence suggests that small open reading frames (sORFs) in ncRNAs can encode micropeptides and polypeptides within 100 amino acids in length. Several micropeptides have been characterized and proven to have various functions in human physiology and pathology, particularly in cancer. The present review mainly highlights the latest studies on ncRNA-encoded micropeptides in different cancers and categorizes them based on their subcellular localization, thereby providing a theoretical basis for micropeptide applications in the early diagnosis and prognosis of cancer and as therapeutic targets. However, considering the inherent characteristics of micropeptides and the limitations of the assay technology methods, more detailed information is warranted.

Ligation-assisted endoscopic mucosal resection for duodenal neuroendocrine tumor.

Endoscopic treatment has become a preferred method for neuroendocrine tumors (NETs) of the gastrointestinal tract.Here we report a 72-year-old female with a duodenal neuroendocrine tumor treated by ligation-assisted endoscopic mucosal resection. This treatment was effectively used to cure the duodenal NETs and ensured complete resection without residual positive margins. This case report is rare.

Clinical observation of dexmedetomidine nasal spray in the treatment of sleep disorders on the first night after undergoing maxillofacial surgery: a single-center double-blind randomized controlled study.

Purpose: Dexmedetomidine exerts a sedative effect by promoting the sleep pathway endogenously and producing a state similar to N2 sleep. This study aimed to study the efficacy and safety of dexmedetomidine nasal spray in the treatment of postoperative sleep disturbance. Methods: This study enrolled 120 participants [men and women; age, 18-40 years; American Society of Anesthesiologists grade, I or II] who underwent maxillofacial surgery under general anesthesia through nasotracheal intubation. The participants were randomly divided into three groups: blank control group (BC group), 1.0 µg/kg dexmedetomidine group (1.0 Dex group), and 1.5 µg/kg dexmedetomidine group (1.5 Dex group), with 40 patients allocated to each group. At 21:30 on the night after the operation, the intervention groups were administered their corresponding doses of dexmedetomidine nasal spray. The Pittsburgh Sleep Quality Index (PSQI) scale was used to evaluate the baseline sleep status of participants 1 month preoperatively and on the night after the operation. Polysomnography (PSG) was used to record the sleep status on the night after the operation. We recorded the rescue times of sedative and analgesic drugs on the first night after surgery, adverse reactions, total hospital stay duration, and total costs. Results: Compared with patients in the BC group, those in 1.0 Dex and 1.5 Dex groups had longer N2 sleep duration, were awake for a shorter time after dose administration, woke up less often, and had significantly improved sleep efficiency (p < 0.05). Compared with the BC group, the PSQI scores of 1.0 Dex and 1.5 Dex groups were significantly lower on the night after operation, and the proportion of PSQI > 5 was significantly lower (p < 0.05). Compared with patients in the BC group and the 1.0 Dex group, those in the 1.5 Dex group had significantly prolonged N3 sleep, reduced frequency of requiring sufentanil rescue, lower incidence of sore throat after surgery, and shorter average length of hospital stay (all, p < 0.05). Conclusion: The sleep quality of participants on the night after having undergone maxillofacial surgery was safely and effectively improved by 1.0-1.5 µg/kg dexmedetomidine atomized nasal sprays. Notably, only the latter could prolong N3 sleep. Level of Evidence II: Evidence was obtained from at least one properly designed randomized controlled trial.

Clinical characteristics of patients with prenatal hydronephrosis in early postnatal period: a single center retrospective study.

BACKGROUND: The study aims to investigate the clinical characteristics of early postnatal period in children with prenatal hydronephrosis (HN) in our single center for 8 years. STUDY DESIGN: The clinical data of 1137 children with prenatal HN from 2012 to 2020 were retrospectively analyzed in our center. Variables of our study mainly included different malformations and urinary tract dilation (UTD) classification, and main outcomes were recurrent hospitalization, urinary tract infection (UTI), jaundice, and surgery. RESULTS: Among the 1137 children with prenatal HN in our center, 188 cases (16.5%) were followed-up in early postnatal period, and 110 cases (58.5%) were found malformations. The incidence of recurrent hospitalization (29.8%) and UTI (72.5%) were higher in malformation, but the incidence of jaundice (46.2%) was higher in non-malformation(P < 0.001). Furthermore, UTI and jaundice were higher in vesicoureteral reflux (VUR) than those in uretero-pelvic junction obstruction (UPJO) (P < 0.05). Meanwhile, Children with UTD P2 and UTD P3 were prone to recurrent UTI, but UTD P0 was prone to jaundice (P < 0.001). In addition, 30 cases (16.0%) of surgery were all with malformations, and the surgical rates of UTD P2 and UTD P3 were higher than those of UTD P0 and UTD P1 (P < 0.001). Lastly, we concluded that the first follow-up should be less than 7 days, the first assessment should be 2 months, and the follow up should be at least once every 3 months. CONCLUSION: Children with prenatal HN have been found many malformations in early postnatal period, and with high-grade UTD were more prone to recurrent UTI, even to surgery. So, prenatal HN with malformations and high-grade UTD should be followed up in early postnatal period regularly.

Acute exposure to microcystins affects hypothalamic-pituitary axes of male rats.

Microcystins (MCs) produced by some cyanobacteria can cause toxicity in animals and humans. In recent years, growing evidence suggests that MCs can act as endocrine disruptors. This research systematically investigated effects of microcystin-LR (MC-LR) on endocrine organs, biosynthesis of hormones and positive/negative feedback of the endocrine system in rats. Male, Sprague-Dawley rats were acutely administrated MC-LR by a single intraperitoneal injection at doses of 45, 67.5 or 90 µg MC-LR/kg body mass (bm), and then euthanized 24 h after exposure. In exposed rats, histological damage of hypothalamus, pituitary, adrenal, testis and thyroid were observed. Serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT), expressions of genes and proteins for biosynthesis of hormones were lesser, which indicated an overall suppression of the hypothalamus-pituitary-adrenal (HPA) axis. Along the hypothalamus-pituitary-gonadal (HPG) axis, lesser concentrations of gonadotropin-releasing hormone (GnRH) and testosterone (T), but greater concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were observed. Except for greater transcription of cyp19a1 in testes, transcriptions of genes and proteins for T and E2 biosynthesis along the HPG axis were lesser. As for the hypothalamus-pituitary-thyroid (HPT) axis, after MCs treatment, greater concentrations of thyroid-stimulating hormone (TSH), but lesser concentrations of free tri-iodothyronine (fT3) were observed in serum. Concentrations of free tetra-iodothyronine (fT4) were greater in rats dosed with 45 µg MCs/kg, bm, but lesser in rats dosed with 67.5 or 90 µg MCs/kg, bm. Transcripts of genes for biosynthesis of hormones and receptors along the HPT axis and expressions of proteins for biosynthesis of tetra-iodothyronine (T4) and tri-iodothyronine (T3) in thyroid were significantly altered. Cross-talk among the HPA, HPG and HPT axes probably occurred. It was concluded that MCs caused an imbalance of positive and negative feedback of hormonal regulatory axes, blocked biosynthesis of key hormones and exhibited endocrine-disrupting effects.

TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation.

Polypeptides encoded by long noncoding RNAs (lncRNAs) are a novel class of functional molecules. However, whether these hidden polypeptides participate in the TP53 pathway and play a significant biological role is still unclear. Here, we discover that TP53-regulated lncRNAs can encode peptides, two of which are functional in various human cell lines. Using ribosome profiling and RNA-seq approaches in HepG2 cells, we systematically identified more than 300 novel TP53-regulated lncRNAs and further confirmed that 15 of these TP53-regulated lncRNAs encode peptides. Furthermore, several peptides were validated by mass spectrometry. Ten of the novel translational lncRNAs are directly inducible by TP53 in response to DNA damage. We show that the TP53-inducible peptides TP53LC02 and TP53LC04, but not their lncRNAs, can suppress cell proliferation. TP53LC04 peptide also has a function associated with cell proliferation by regulating the cell cycle in response to DNA damage. This study shows that TP53-regulated lncRNAs can encode new functional peptides, leading to the expansion of the TP53 tumor-suppressor network and providing novel potential targets for cancer therapy.

Molecular mechanism of m6A methylation of circDLC1 mediated by RNA methyltransferase METTL3 in the malignant proliferation of glioma cells.

Glioma is an intracranial malignant tumor and remains largely incurable. Circular RNAs are prominent modulators in glioma progression. This study investigated the function of circular RNA DLC1 (circDLC1) in the malignant proliferation of glioma cells. circDLC1 expression in glioma tissues and cells was determined using RT-qPCR. The effect of circDLC1 on the malignant proliferation of glioma cells was analyzed using CCK-8, colony formation, and EdU staining assays. METTL3, miR-671-5p, and CTNNBIP1 expressions were determined. N6 methyladenosine (m6A) level of circDLC1 was analyzed using MeRIP. The binding relationship between miR-671-5p and circDLC1 or CTNNBIP1 was verified using RNA pull-down and dual-luciferase assays. A xenograft tumor model was established in nude mice to verify the effect of METTL3-mediated circDLC1 on glioma in vivo. circDLC1 was poorly expressed in glioma. circDLC1 overexpression suppressed glioma cell proliferation. Mechanically, METTL3-mediated m6A modification enhanced circDLC1 stability and upregulated circDLC1 expression in glioma. circDLC1 upregulated CTNNBIP1 transcription by competitively binding to miR-671-5p. METTL3 overexpression repressed the malignant proliferation of glioma via circDLC1/miR-671-5p/CTNNBIP1 in vivo. Collectively, METTL3-mediated m6A modification upregulated circDLC1 expression, and circDLC1 promoted CTNNBIP1 transcription by sponging miR-671-5p, thus repressing the malignant proliferation of glioma.

IMM-H007 attenuates isoprenaline-induced cardiac fibrosis through targeting TGFß1 signaling pathway.

Upon chronic stress, ß-adrenergic receptor activation induces cardiac fibrosis and leads to heart failure. The small molecule compound IMM-H007 has demonstrated protective effects in cardiovascular diseases via activation of AMP-activated protein kinase (AMPK). This study aimed to investigate IMM-H007 effects on cardiac fibrosis induced by ß-adrenergic receptor activation. Because adenosine analogs also exert AMPK-independent effects, we assessed AMPK-dependent and -independent IMM-H007 effects in murine models of cardiac fibrosis. Continual subcutaneous injection of isoprenaline for 7 days caused cardiac fibrosis and cardiac dysfunction in mice in vivo. IMM-H007 attenuated isoprenaline-induced cardiac fibrosis, diastolic dysfunction, α-smooth muscle actin expression, and collagen I deposition in both wild-type and AMPKα2-/- mice. Moreover, IMM-H007 inhibited transforming growth factor ß1 (TGFß1) expression in wild-type, but not AMPKα2-/- mice. By contrast, IMM-H007 inhibited Smad2/3 signaling downstream of TGFß1 in both wild-type and AMPKα2-/- mice. Surface plasmon resonance and molecular docking experiments showed that IMM-H007 directly interacts with TGFß1, inhibits its binding to TGFß type II receptors, and downregulates the Smad2/3 signaling pathway downstream of TGFß1. These findings suggest that IMM-H007 inhibits isoprenaline-induced cardiac fibrosis via both AMPKα2-dependent and -independent mechanisms. IMM-H007 may be useful as a novel TGFß1 antagonist.

Comparison of the Sedative and Analgesic Effects of Dexmedetomidine-Remifentanil and Dexmedetomidine-Sufentanil for Liposuction: A Prospective Single-Blind Randomized Controlled Study.

BACKGROUND: Dexmedetomidine had sedative and analgesic effects and did not produce significant respiratory depression at therapeutic doses. AIMS: To compare the sedative and analgesic effects and safety of dexmedetomidine combined with remifentanil or sufentanil in patients undergoing liposuction. METHODS: A total of 100 subjects were randomized 1:1 to two groups: Group R and Group S. First, patients were administered midazolam 0.02 mg·kg-1. Anesthesia was induced with an intravenous infusion of dexmedetomidine 1 µg kg-1 (15 min) and remifentanil 0.1 µg kg-1 min-1 (Group R) or sufentanil 0.1 µg kg-1h-1 (Group S). Anesthesia was maintained with an intravenous infusion of dexmedetomidine 1.0 µg kg-1h-1, midazolam 0.015 mg kg-1h-1, remifentanil 0.1 µg kg-1min-1 (Group R), or sufentanil 0.1 µg kg-1h-1 (Group S). Hemodynamic and respiratory changes, modified OAA/S score and BIS values, postoperative Visual Analogue Scale pain scores, satisfaction of the patient and surgical team with the procedure, and adverse events and recovery time were recorded. RESULTS: Group R received significantly less midazolam and midazolam per hour compared to Group S (Group R vs. Group S: 3.4 ± 1.7 mg vs. 5.1 ± 2.0 mg, P < 0.0001; 1.5 ± 0.7 mg/h vs. 1.9 ± 0.6 mg/h, P = 0.002). The incidence of physical or verbal expressions of pain at the start of surgery was significantly lower in Group R compared to Group S (2 [4.3%] vs. 12 [26.7%], P = 0.003). Patient satisfaction with the procedure was significantly higher in Group R compared to Group S (3.9 ± 0.3 vs. 3.1 ± 0.3, P < 0.0001). CONCLUSION: Dexmedetomidine-remifentanil and dexmedetomidine-sufentanil were effective and safe sedative and analgesic agents for liposuction. Hemodynamic stability was maintained. Dexmedetomidine-remifentanil might be associated with improved analgesic effects compared to dexmedetomidine-sufentanil. LEVEL OF EVIDENCE II: Evidence was obtained from at least one properly designed randomized controlled trial. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A national descriptive epidemiologic analysis on congenital pulmonary airway malformation in China, 2010-2019.

OBJECTIVE: To depict the epidemiological features of congenital pulmonary airway malformation (CPAM) in Chinese population. METHODS: Using 2010-2019 data from the Chinese Birth Defects Monitoring Network, we calculated the prevalence rates (PR) and 95% confidence intervals of isolated and nonisolated CPAM according to birth year, infant sex, maternal age and residence area, and examined the secular trends by using Poisson regression models. The perinatal outcomes of affected infants and associated malformations with CPAM were also analyzed. RESULTS: During this period, a total of 2451 CPAMs were identified among 20,183,999 births, yielding a PR of 1.21, 0.95, and 0.27 per 10,000 live and still births for the overall, isolated and nonisolated CPAM, respectively. Significant upward trends in CPAM PR were observed. The PR varied significantly by infant sex (male vs. female, 1.28/10,000 vs. 1.10/10,000), residence area (urban vs. rural, 1.49/10,000 vs. 0.88/10,000), and by maternal age (<20 years, 0.94/10,000; 20-24 years, 1.04/10,000; 25-29 years, 1.32/10,000; 30-34 years, 1.28/10,000; ≥35 years, 1.05/10,000). Compared with isolated CPAM, much more live births with nonisolated CPAM died in the early neonatal period (5.0% vs. 1.0%). The additional malformations with nonisolated CPAM occurred most frequently in the circulatory system. CONCLUSIONS: The PR of CPAM in this study are comparable to those reported in non-Chinese populations. The increasing trend in prevalence and poor perinatal outcomes of the affected infants indicate an urgent need to strengthen the clinical and public health interventions of CPAM.

Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/ß-catenin signaling.

Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/ß-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/ß-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/ß-catenin activation. Besides, pharmacological inhibition of Wnt/ß-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/ß-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients.

Decreased granzyme B+CD19+B cells are associated with tumor progression following liver transplantation.

Lymphocytes play an important role in antitumor immunity following organ transplantation. However, the function of granzyme B+CD19+B cells on the hepatocellular carcinoma cells from liver transplant recipients remains largely unknown; we aimed to analyze the function and elucidate the mechanisms behind it. Blood samples and clinical data from liver transplant recipients and healthy controls at Beijing Chaoyang Hospital as well as from a validation cohort were collected and analyzed. In this study, we found decreased granzyme B+CD19+B cells were correlated with early hepatocellular carcinoma recurrence and could further identify liver transplant recipients with poor tumor differentiation, microvascular invasion, increased total tumor diameter, and tumor beyond Milan criteria. Notably, granzyme B+CD19+B cells directly inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells. Upon activation regulatory B cells from liver transplant recipients with hepatocellular carcinoma recurrence displayed a CD5+CD38+CD27+CD138+CD19+ granzyme B+ phenotype, but the increased expression of CD5, CD38, and CD138, and the decreased protein level and transcriptional level requiring JAK/STAT signaling. In an independent validation cohort, liver transplant recipients with decreased granzyme B+CD19+B cells had not only early hepatocellular carcinoma cell recurrence but also shorter survival. Our study provides comprehensive data from liver transplant recipients with hepatocellular carcinoma, indicating a critical role of granzyme B+CD19+B cells in preventing cancer progression. Our findings warrant further investigations for the design of future immunotherapies leading to immune responses and improved patient survival.