Construction of blackberry polysaccharide nano-selenium particles: Structure features and regulation effects of glucose/lipid metabolism in HepG2 cells.

In this study, blackberry polysaccharide-selenium nanoparticles (BBP-24-3Se) were first prepared via Na2SeO3/Vc redox reaction, followed by coating with red blood cell membrane (RBC) to form core-shell structure polysaccharide-selenium nanoparticles (RBC@BBP-24-3Se). The particle size of BBP-24-3Se (167.1 nm) was increased to 239.8 nm (RBC@BBP-24-3Se) with an obvious core-shell structure after coating with RBC. FT-IR and XPS results indicated that the interaction between BBP-24-3 and SeNPs formed a new C-O···Se bond with valence state of Se0. Bioassays indicated that RBC coating markedly enhanced both the biocompatibility and bioabsorbability of RBC@BBP-24-3Se, and the absorption rate of RBC@BBP-24-3Se in HepG2 cells was 4.99 times higher than that of BBP-24-3Se at a concentration of 10 µg/mL. Compared with BBP-24-3Se, RBC@BBP-24-3Se possessed significantly heightened protective efficacy against oxidative damage and better regulation of glucose/lipid metabolism disorder induced by palmitic acid in HepG2 cells. Mechanistic studies demonstrated that RBC@BBP-24-3Se could effectively improve PI3K/AKT signaling pathway to promote glucose metabolism, inhibit the expression of lipid synthesis genes and up-regulate the expression of lipid-decomposing genes through AMPK signaling pathway to improve lipid metabolism. These results provided a theoretical basis for developing a new type of selenium supplement for the treatment of insulin resistance.

Case Report: Two cases of advanced primary cardiac angiosarcoma treated with anlotinib and a retrospective analysis of the literature.

Primary cardiac angiosarcoma is a rare malignant soft-tissue sarcoma derived from vascular endothelial cells or lymphatic endothelial cells, with a high malignancy, poor prognosis, and a lack of effective medical therapy. This article reports on two patients with primary cardiac angiosarcoma who received first-line treatment with multi-targeted anti-angiogenic agent, anlotinib monotherapy. The treatment rapidly controlled pleural and pericardial effusion, significantly reduced the tumor, improved symptoms, and showed satisfactory recent efficacy. This indicates that anlotinib offers a new first-line treatment option for advanced primary cardiac angiosarcoma.

A large deletion in TSC2 causes tuberous sclerosis complex by dysregulating PI3K/AKT/mTOR signaling pathway.

BACKGROUND/AIM: Tuberous sclerosis complex (TSC) is a multi-system syndrome caused by loss-of-function mutation in TSC1 or TSC2. Most TSC patients present with cardiac rhabdomyoma or cortical tubers during fetal life, and the symptoms are not uniform as their age. The gene products of TSC1/2 are components of the TSC protein complex and are important role in the PI3K/AKT/mTOR (PAM) signaling pathway. Based on three members of a family with variable expressivity, the purpose of this study was to clarify the clinical features of TSC in different age groups and to analyze the genetic characteristics of TSC2 gene. METHODS: Clinical exome sequencing and co-segregation were used to identify a three-generation family with four affected individuals. HEK-293T cell model was constructed for subsequent experiments. Quantitative RT-PCR, western blotting, and subcellular localization were used to analyze the expression effect of TSC2 mutation. CCK-8 assay, wound healing assay, and cell cycle analysis were used to analyze the function effect of TSC2 mutation. RESULT: We identified a TSC family with heterozygous deletion of exon 4 in TSC2 by clinical exon sequencing. Sanger sequencing indicated that the affected individuals have 2541-bp deletion that encompassed exon 4 and adjacent introns. Deletion of exon 4 decreased the TSC2 mRNA and protein levels in HEK-293T cells, and activated the PI3K/AKT/mTOR pathway, thereby altering the cell cycle and promoting cell proliferation and migration. CONCLUSION: We confirmed the pathogenicity of the large deletion in TSC2 in a three- generations family.. Deletion of exon 4 of TSC2 affected cell proliferation, migration, and cell cycle via abnormal activation of the PAM pathway. This study evaluated the pathogenic effect of deletion of exon 4 of TSC2 and investigated the underlying mechanism.

Effect of probiotics and fecal microbiota transplantation in dirty rats with established primary liver cancer.

Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials & methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of ß-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.

A novel APC mutation associated with Gardner syndrome in a Chinese family.

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

Intravenous Administration of an AAV9 Vector Ubiquitously Expressing C1orf194 Gene Improved CMT-Like Neuropathy in C1orf194-/- Mice.

Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor sensory neuropathy, is a group of rare genetically heterogenous diseases characterized by progressive muscle weakness and atrophy, along with sensory deficits. Despite extensive pre-clinical and clinical research, no FDA-approved therapy is available for any CMT type. We previously identified C1ORF194, a novel causative gene for CMT, and found that both C1orf194 knock-in (I121N) and knockout mice developed clinical phenotypes similar to those in patients with CMT. Encouraging results of adeno-associated virus (AAV)-mediated gene therapy for spinal muscular atrophy have stimulated the use of AAVs as vehicles for CMT gene therapy. Here, we present a gene therapy approach to restore C1orf194 expression in a knockout background. We used C1orf194-/- mice treated with AAV serotype 9 (AAV9) vector carrying a codon-optimized WT human C1ORF194 cDNA whose expression was driven by a ubiquitously expressed chicken ß-actin promoter with a CMV enhancer. Our preclinical evaluation demonstrated the efficacy of AAV-mediated gene therapy in improving sensory and motor abilities, thus achieving largely normal gross motor performance and minimal signs of neuropathy, on the basis of neurophysiological and histopathological evaluation in C1orf194-/- mice administered AAV gene therapy. Our findings advance the techniques for delivering therapeutic interventions to individuals with CMT.

Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis.

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

Effectiveness of tislelizumab when combined with etoposide and carboplatin in patients with SMARCA4-deficient undifferentiated thoracic tumor: a case report.

Background: SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare malignant condition with high invasiveness and poor prognosis. Presently, no clear guidelines are available for the treatment of SMARCA4-UT. The median overall survival was only four to seven months. Several patients are diagnosed in advanced stages of the malignancy and do not respond to conventional radiotherapy and chemotherapy. Case Description: A 51-year-old Chinese man was diagnosed with a SMARCA4-UT. The patient did not have a chronic history of hypertension or diabetes and any family history of malignant tumors. No sensitive mutation in lung cancer-related ten genes was identified. The first-line therapy with four cycles of liposomal paclitaxel and cisplatin combined with two cycles of tyrosine kinase inhibitor anlotinib failed. On immunohistochemical analysis, no programmed cell death 1 ligand 1 (PD-L1) expression was found. However, whole-exon sequencing revealed a high tumor mutation burden (TMB) of 15.95 mutations/Mb with TP53 and KEAP1 mutations. The patient was treated with a second-line regimen containing tislelizumab, etoposide, and carboplatin (TEC). A reduction in tumor burden was seen for more than 10 months. Conclusions: The case of SMARCA4-UT with a high mutation burden successfully responded to the combined regimen containing TEC. This could be a new treatment option for patients with SMARCA4-UTs.

A novel single-base deletion of the RUNX Family Transcription Factor 2 gene associated with cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a rare, autosomal dominant hereditary disorder characterized by skeletal malformations and dental abnormalities. The purpose of this study was to explore the functional role of a novel mutation in the pathogenesis of CCD. Genomic DNA was extracted from peripheral blood mononuclear cells collected from family members of a Chinese patient with CCD. An analysis of their RUNX Family Transcription Factor 2 (RUNX2) gene sequences was performed by PCR amplification and Sanger sequencing. The function of the mutant RUNX2 was studied by bioinformatics, real-time PCR, western blotting, and subcellular localization analysis. Sanger sequencing identified a novel single-base deletion (NM_001024630.4:c.132delG;NP_001019801.3: Val45Trpfs* 99) in the RUNX2 gene present in the Chinese patient with CCD. In vitro, functional studies showed altered protein localization and increased expression of mutant RUNX2 mRNA and mutant Runt-related transcription factor 2 (RUNX2). Luciferase reporter assay demonstrated that the novel RUNX2 mutations significantly increased the transactivation activity of RUNX2 on the osteocalcin gene promoter. In conclusion, we identified a patient with sporadic CCD carrying a novel deletion/frameshift mutation of the RUNX2 gene and performed screening and functional analyses to determine the cause of the CCD phenotype. This study provides new insights into the pathogenesis of CCD.3.

Transarterial viroembolization improves the therapeutic efficacy of immune-excluded liver cancer: Three birds with one stone.

OBJECTIVE: To investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models. MATERIALS AND METHODS: Subcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured. RESULTS: The optimal viral titer of OH2 was 1 × 107 CCID50. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies. CONCLUSION: TAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice. DATA AVAILABILITY: Data is available from the corresponding author upon requirement.

Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. CASE PRESENTATION: In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. CONCLUSION: This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study.

Objectives: To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. Results: There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2-25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable. Conclusion: TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.

Assessing the robustness of radiomics/deep learning approach in the identification of efficacy of anti-PD-1 treatment in advanced or metastatic non-small cell lung carcinoma patients.

Administration of anti-PD-1 is now a standard therapy in advanced non-small cell lung carcinoma (NSCLC) patients. The clinical application of biomarkers reflecting tumor immune microenvironment is hurdled by the invasiveness of obtaining tissues despite its importance in immunotherapy. This study aimed to develop a robust and non-invasive radiomics/deep learning machine biomarker for predicting the response to immunotherapy in NSCLC patients. Radiomics/deep learning features were exacted from computed tomography (CT) images of NSCLC patients treated with Nivolumab or Pembrolizumab. The robustness of radiomics/deep learning features was assessed against various perturbations, then robust features were selected based on the Intraclass Correlation Coefficient (ICC). Radiomics/deep learning machine-learning classifiers were constructed by combining seven feature exactors, 13 feature selection methods, and 12 classifiers. The optimal model was selected using the mean area under the curve (AUC) and relative standard deviation (RSD). The consistency of image features against various perturbations was high (the range of median ICC: 0.78-0.97), but the consistency was poor in test-retest testing (the range of median ICC: 0.42-0.67). The optimal model, InceptionV3_RELF_Nearest Neighbors classifiers, had the highest prediction efficacy (AUC: 0.96 and RSD: 0.50) for anti-PD-1/PD-L1 treatment. Accuracy (ACC), sensitivity, specificity, precision, and F1 score were 95.24%, 95.00%, 95.50%, 91.67%, and 95.30%, respectively. For successful model robustification, tailoring perturbations for robustness testing to the target dataset is key. Robust radiomics/deep learning features, when paired with machine-learning methodologies, will work on the exactness and the repeatability of anticipating immunotherapy adequacy.

Identification of a novel missense heterozygous mutation in the KDF1 gene for non-syndromic congenital anodontia.

OBJECTIVES: KDF1 is a recently identified gene related to tooth development, but it has been little studied. To date, only three cases have been reported in which KDF1 mutations are related to tooth development, including two ectodermal dysplasia cases accompanied by tooth loss and one non-syndromic case with tooth agenesis. However, no KDF1 mutations have been reported as associated with non-syndromic anodontia. Here, the aim was to investigate the genetic etiology of this condition and explore the functional role of a novel KDF1 mutation in a Chinese patient with non-syndromic anodontia. MATERIALS AND METHODS: Pathogenic variants were identified by whole-exome and Sanger sequencing. Meanwhile, we conducted a literature review of the reported KDF1 mutations and performed an in vitro functional analysis of four anodontia-causing KDF1 mutations (one novel and three known). RESULTS: We identified a novel de novo missense mutation (c.911 T > A, p.I304N) in the KDF1 gene in a Chinese patient with severe non-syndromic anodontia. In vitro functional studies showed altered mRNA and protein expression levels of the mutant KDF1. CONCLUSIONS: Our results are the first report of KDF1 missense mutation causing non-syndromic anodontia. CLINICAL RELEVANCE: This study not only further supports the important role of KDF1 in non-syndromic congenital anodontia, but also expands the spectrum of KDF1 mutations and will contribute to the genetic diagnosis and counselling of families with anodontia.

A Heterozygous LMF1 Gene Mutation (c.1523C>T), Combined With an LPL Gene Mutation (c.590G>A), Aggravates the Clinical Symptoms in Hypertriglyceridemia.

Hypertriglyceridemia is an important contributor to atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis. Familial hypertriglyceridemia is often caused by mutations in genes involved in triglyceride metabolism. Here, we investigated the disease-causing gene mutations in a Chinese family with hypertriglyceridemia and assessed the functional significance in vitro. Whole-exome sequencing (WES) was performed revealing that the severe hypertriglyceridemic proband carried a missense mutation (c.590G > A) in exon 5 of the LPL gene, as well as a missense mutation (c.1523C > T) in exon 10 of the LMF1 gene. Conservation analysis by Polyphen-2 showed that the 508 locus in the LMF1 protein and 197 locus in the LPL protein were highly conserved between different species. I-TASSER analysis indicated that the LMF1 c.1523C > T mutation and the LPL c.590G > A mutation changed the tertiary structure of the protein. A decrease in mRNA and protein expression was observed in 293T cells transfected with plasmids carrying the LMF1 c.1523C > T mutation. Subcellular localization showed that both wild-type (WT) and mutant LMF1 protein were localized at the cell cytoplasm. In the cell medium and cell lysates, these LMF1 and LPL gene mutations both caused a decreased LPL mass. Moreover, the combination of LMF1 and LPL gene mutations significantly decreased LPL levels compared to their individual effects on the LPL concentration. Both the clinical and in vitro data suggest that severe hypertriglyceridemia was of digenic origin caused by LMF1 and LPL mutation double heterozygosity in this patient.

Transarterial chemoembolization combined with camrelizumab for recurrent hepatocellular carcinoma.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.

Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma.

OBJECTIVES: The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. RESULTS: A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. CONCLUSIONS: D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C.

Tumor feeding artery contraction and metastasis inhibition after transarterial chemoembolization combined with apatinib for hepatocellular carcinoma: A propensity score matching study.

AIM: To investigate the change of tumor feeding artery diameter and the efficacy of metastasis inhibition after transarterial chemoembolization (TACE) combined with apatinib or TACE monotherapy for patients with advanced hepatocellular carcinoma who without metastasis. MATERIALS AND METHODS: A total of 616 consecutive patients who received the treatment of TACE-apatinib or TACE in our center was enrolled. Propensity score matching (PSM) analysis was used to reduce bias. The overall survival (OS), OS-after-metastasis (OSM), time to progression (TTP), time to metastasis (TTM), time to vessel or organ metastasis (TVOM), time to lymph node metastasis, and tumor feeding artery diameter between the two treatment groups were compared. RESULTS: A total of 113 pairs of patients were eligible after the PSM. Time to lymph node metastasis between the two groups was not significantly different (P > 0.05). The tumor feeding artery diameter was significantly smaller after TACE-apatinib management (P < 0.001). Median OS (P < 0.001) and OSM (P < 0.001) were significantly longer in the TACE-apatinib group compared with the TACE group. Median TTP (P < 0.001), TTM (P < 0.001), and TVOM (P < 0.001) were significantly prolonged in TACE-apatinib group. CONCLUSION: TACE-apatinib treatment could improve the prognosis compared with TACE alone, and inhibit metastasis after TACE procedure with contracted tumor feeding artery for advanced HCCs without metastasis.

Familial Translocation t(2;4) (q37.3;p16.3), Resulting in a Partial Trisomy of 2q (or 4p) and a Partial Monosomy of 4p (or 2q), Causes Dysplasia.

Background: Wolf-Hirschhorn syndrome, a well-known contiguous microdeletion syndrome, is caused by deletions on chromosome 4p. While the clinical symptoms and the critical region for this disorder have been identified based on genotype-phenotype correlations, duplications in this region have been infrequently reported. Conclusion: Our case report shows that both deletions and duplications of the Wolf-Hirshhorn critical region cause intellectual disability/developmental delay and multiple congenital anomalies.

Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease.

Rationale: Renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) can originate from any nephron segments, including proximal tubules (PT), the loop of Henle (LOH), distal tubules (DT), and collecting ducts (CD). Previous studies mostly used limited cell markers and failed to identify cells negative for these markers. Therefore, the cell composition and origin of ADPKD cyst are still unclear, and mechanisms of cystogenesis of different origins await further exploration. Methods: We performed single-cell RNA sequencing for the normal kidney tissue and seven cysts derived from superficial or deep layers of the polycystic kidney from an ADPKD patient. Results: Twelve cell types were identified and analyzed. We found that a renal cyst could be derived either from CD or both PT and LOH. Gene set variation analysis (GSVA) showed that epithelial mesenchymal transition (EMT), TNFA signaling via the NFKB pathways, and xenobiotic metabolism were significantly activated in PT-derived cyst epithelial cells while robust expression of genes involved in G2M Checkpoint, mTORC1 signaling, E2F Targets, MYC Targets V1, MYC Targets V2 were observed in CD-derived cells. Conclusion: Our results revealed that a single cyst could originate from CD or both PT and LOH, suggesting heterogeneity of polycystic composition and origin. Furthermore, cyst epithelial cells with different origins have different gene set activation.