Case Report: Imaging features of a new type double inferior vena cava malformation and review.

Background: Double inferior vena cava (DIVC) is a rare vascular malformation. With advances in radiological techniques and diagnosis, more and more types of DIVC were identified and diagnosed. Recognition of the variety of DIVC seen on imaging is essential for subsequent venous interventions. Case presentation: A 77-year-old man presented with low back pain with left lower limb pain for 1 month. Scattered petechiae above the skin surface on the left lower leg, especially on the extensor surface, with flaking and mild tingling of the skin, were noted 3 weeks ago. Ultrasound revealed deep vein thrombosis (DVT) in the left lower limb. Computed tomography pulmonary angiography (CTPA) suggested no significant thrombus in the pulmonary artery. Computed tomography venography (CTV) of bilateral lower limbs showed that iliac vein compression syndrome with formation of deep and superficial venous traffic branches in bilateral lower limbs, predominantly on the left side. CTV of the inferior vena cava (IVC) suggested that the left common iliac vein crossed the common iliac artery bifurcation from dorsal to ventral and continued to travel cranially as a ventral vessel, and connected with the ventral IVC anterior to the right common iliac artery. The right common iliac vein extended cephalad as a dorsal vessel, which was narrowed at the level of 4th lumbar vertebra by compression of the hyperplastic bone and the osteophyte. The patient was discharged after right and left common iliac vein angiography and balloon dilation of bilateral common iliac vein. Conclusion: The formation of both ventrally and dorsally aligned DIVC is rarer. It should be clarified the effects of DIVC on DVT formation, and the importance of imaging for preoperative planning.

Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt-Hogg-Dubé syndrome.

To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt-Hogg-Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fumarate hydratase (FH)-deficient papillary RCC via pathological biopsy carried two heterozygous variants: FH (NM_000143.3) missense mutation c.1189G>A (p.Gly397Arg) and FLCN (NM_144997.5) frameshift mutation c.1579_1580insA (p.Arg527Glnfs*75). No family member carrying a single variant had renal tumours. In HEK293T cells transfected with mutant vectors, mRNA and protein expression after FLCN p.Arg527Glnfs*75 and FH p.Gly397Arg mutations were significantly lower than those in wild-type (WT) cells. Cell immunofluorescence showed altered protein localisation and reduced protein expression after FLCN p.Arg527Glnfs*75 mutation. The FH WT was uniformly distributed in the cytoplasm, whereas FH protein expression was reduced after the p.Gly397Arg mutation and scattered sporadically with altered cell localisation. Patients with two variants may have a significantly increased penetrance of RCC.

MiR-125b and SATB1-AS1 might be shear stress-mediated therapeutic targets.

The aim of the study was to explore the potential molecular mechanism associated with shear stress on abdominal aortic aneurysm (AAA) progression. This study performed RNA sequencing on AAA patients (SQ), AAA patients after endovascular aneurysm repair (EVAR, SH), and normal controls (NC). Furthermore, we identified the differentially expressed microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNA (cirRNAs) and constructed competing endogenous RNA (ceRNA) networks. Finally, 164 differentially expressed miRNAs, 179 co-differentially expressed lncRNAs, and 440 co-differentially expressed circRNAs among the three groups were obtained. The differentially expressed miRNAs mainly enriched in 325 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Target genes associated with co-differentially expressed genes among the group of SH, SQ, and NC mainly enriched in 66 KEGG pathways. LncRNA-miRNA-mRNA interactions, including 15 lncRNAs, 63 miRNAs and 57 mRNAs, was constructed. CircRNA-miRNA-mRNA ceRNA network included 79 circRNAs, 21 miRNAs, and 49 mRNAs. Among them, KLRC2 and CSTF1, targeted by miR-125b, participated in cell-mediated immunity regulation. MiR-320-related circRNAs and SATB1-AS1 serving as the sponge of miRNAs, such as has-circ-0129245, has-circ-0138746, and has-circ-0139786, were hub genes in ceRNA network. In conclusion, AAA patients might be benefit from EVAR based on various pathways and some molecules, such as miR-125b and SATB1-AS1, related with shear stress.

lncRNA ANRIL accelerates wound healing in diabetic foot ulcers via modulating HIF1A/VEGFA signaling through interacting with FUS.

BACKGROUND: Diabetic foot ulcer (DFU) is a frequently diagnosed complication of diabetes, and remains a heathcare burden worldwide. However, the pathogenesis of DFU is still largely unclear. The objective of this study is to delineate the function and underlying mechanism of lncRNA antisense non coding RNA in the INK4 locus (ANRIL) in endothelial progenitor cells (EPCs) and DFU mice. METHODS: The DFU mouse model was established, and EPCs were subjected to high glucose (HG) treatment to mimic diabetes. qRT-PCR or western blot was employed to detected the expression of ANRIL, HIF1A, FUS and VEGFA. CCK-8 and Annexin V/PI staining were used to monitor cell proliferation and apoptosis. Wound healing, Transwell invasion and tube formation assays were conducted to assess cell migration, invasion and angiogenesis, respectively. The association between ANRIL and FUS was verified by RNA pull-down and RIP assays. Luciferase and ChIP assays were employed to investigate HIF1A-mediated transcriptional regulation of VEGFA and ANRIL. The histological alterations of DFU wound healing were observed by H&E and Masson staining. RESULTS: ANRIL was downregulated in peripheral blood samples of DFU patients, DFU mice and HG-treated EPCs. Mechanistically, ANRIL regulated HIFA mRNA stability via recruiting FUS. VEGFA and ANRIL were transcriptionally regulated by HIF1A. Functional experiments revealed that HG suppressed EPC proliferation, migration, invasion and tube formation, but promoted apoptosis via ANRIL/HIF1A axis. ANRIL accelerated DFU wound healing via modulating HIF1A expression in vivo. CONCLUSION: ANRIL accelerated wound healing in DFU via modulating HIF1A/VEGFA signaling in a FUS-dependent manner.

Comprehensive analysis of immune ferroptosis gene in renal clear cell carcinoma: prognosis and influence of tumor microenvironment.

OBJECTIVE: We conducted an in-depth study of the immune system and ferroptosis to identify prognostic biomarkers and therapeutic targets for renal clear cell carcinoma. METHODS: Immune ferroptosis-related differentially expressed genes (IFR-DEGs) were selected from The Cancer Genome Atlas (TCGA). A lasso-Cox risk scoring model was established; its prognostic value was determined using prognostic analysis and single multivariate Cox analysis. Model genes were subjected to subcellular fluorescence localization, mRNA and protein expression analyses, and single-cell RNA sequencing localization analysis. Risk score was analyzed using the immune score, immune infiltrating cell correlation, immune checkpoint, TIDE, and drug sensitivity. RESULTS: A total of 103 IFR-DEGs were identified; a risk model comprising ACADSB, CHAC1, LURAP1L, and PLA2G6 was established. The survival curve, single multivariate Cox regression, and receiver operating characteristic (ROC) curve analysis showed that the model had good predictive ability (p < 0.05). It was also validated using the validation set and total cohort. Subcellular fluorescence localization revealed that ACADSB, CHAC1, and PLA2G6 were distributed in the cytoplasm and LURAP1L in the nucleus. The mRNA and protein expression trends were consistent. Single-cell RNA sequencing mapping revealed that ACADSB was enriched in distal tubule cell clusters. In the Kidney renal clear cell carcinoma (KIRC) mutation correlation analysis, 1.56% of the patients were found to have genetic alterations; The Spearman correlation analysis of model gene mutations showed that ACADSB was positively correlated with LURAP1L, which may have a synergistic effect; it was negatively correlated with CHAC1 and PLA2G6, and CHAC1 was negatively correlated with LURAP1L, which may have an antagonistic effect. Model and immune correlation analyses found that high-risk patients had significantly higher levels of CD8+ T cells, regulatory T cells (Tregs), immune checkpoints, immune scores, and immune escape than those in low-risk patients. High-risk patients had a higher susceptibility to small-molecule drugs. CONCLUSION: A novel prognostic model of immune ferroptosis-related genes (ACADSB, CHAC1, LURAP1L, and PLA2G6), which plays an important role in immune infiltration, microenvironment, and immune escape, was constructed. It effectively predicts the survival of patients with KIRC.

MiR-137 regulates low-intensity shear stress-induced human aortic endothelial cell apoptosis via JNK/AP-1 signaling.

The objective of this study is to evaluate the role of miR-137 in low-intensity shear stress-induced endoplasmic reticulum (ER) stress and cell apoptosis in human aortic endothelial cells (HAECs). HAECs were transfected with miR-137 mimic, miR-137 inhibitor, or the corresponding negative control and then exposed to pulsatile shear stress in a parallel-plate flow chamber at 1, 2, 5, 10, and 15 dyn/cm2 for 3 h. Real-time polymerase chain reaction was used to detect mRNA expression of miR-137 and SDS22. A dual-luciferase reporter assay was employed to verify the direct interaction between miR-137 and SDS22. The internal morphology of cells and cell apoptosis was assessed by TUNEL staining observed under a transmission electron microscope. Meanwhile, the protein expression of oxidative stress-related, apoptosis-related, and activated c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling-related genes were analyzed by western blotting. Low strength shear stress (0-5 dyn/cm2) caused a negative change of HAEC surface and internal morphology in an intensity-dependent manner, and these changes were gradually weakened when shear stress was increased more than 5 dyn/cm2. Furthermore, low-intensity shear stress promoted oxidative stress response, accelerated cell apoptosis, and upregulated miR-137 expression and JNK/AP-1 signaling in HAECs. MiR-137 directly targets SDS22. Knockdown of miR-137 noticeably reduced activation of JNK/AP-1 signaling, oxidative stress response, and cell apoptosis induced by shear stress. MiR-137 regulated low-intensity shear stress-induced human aortic endothelial cell ER stress and cell apoptosis via JNK/AP-1 signaling.

MiR-214 sensitizes human colon cancer cells to 5-FU by targeting Hsp27.

Overcoming chemorestistance to 5-fluorouracil (5-FU) could offer a new treatment option for highly malignant colon cancer. In our study, differential microRNA expression profiling revealed that miR-214 is downregulated in 5-FU-resistant colon cancer cells compared to normal cells. In vitro, miR-214 could sensitize non-resistant colon cancer cells and 5-FU-resistant colon cancer cellsto 5-FU. Functionally, miR-214 inhibited cell clone formation and cell growth and enhanced 5-FU-inducing cell apoptosis and caspase-3 levels. MiR-214 targeted heat shock protein 27 (Hsp27), as confirmed via dual luciferase reporter assays and western blots. Hsp27 also sensitized HT-29 and LoVo to 5-FU by enhancing cell apoptosis. Overexpression of Hsp27 could block miR-214 with an effect on the sensitivity of colon cancer cells to 5-FU. In conclusion, miR-214 sensitizes colon cancer cells to 5-FU by targeting Hsp27, indicating a significant role for this miRNA in colon cancer chemotherapy.

Slit2 suppresses endothelial cell proliferation and migration by inhibiting the VEGF-Notch signaling pathway.

Slit homolog 2 (Slit2) is distributed in various tissues and participates in numerous cellular processes; however, the role of Slit2 in the regulation of angiogenesis remains controversial, since it has previously been reported to exert proangiogenic and antiangiogenic activities. The present study aimed to investigate the effects of Slit2 on vascular endothelial cell proliferation and migration in vitro, and to reveal the possible underlying signaling pathway. Aortic endothelial cells were isolated from Sprague Dawley rats and cultured. Cell proliferation assay, cell migration assay, immunocytochemistry and small interfering RNA transfection were subsequently performed. The results demonstrated that exogenous Slit2 administration markedly suppressed TNF­α­induced endothelial cell proliferation and migration in vitro. In addition, TNF­α application upregulated the protein expression levels of vascular endothelial growth factor (VEGF) and Notch in RAECs, whereas Slit2 administration downregulated VEGF and Notch expression in RAECs cultured in TNF­α conditioned medium. Further studies indicated that knockdown of VEGF suppressed the effects of TNF­α on the induction of RAEC proliferation and migration. VEGF knockdown­induced inhibition of RAEC proliferation and migration in TNF­α conditioned medium was also achieved without Slit2 administration. Furthermore, VEGF knockdown markedly decreased Notch1 and Notch2 expression. These results indicated that Slit2 suppresses TNF­α­induced vascular endothelial cell proliferation and migration in vitro by inhibiting the VEGF­Notch signaling pathway. Therefore, Slit2 may inhibit the proliferation and migration of endothelial cells during vascular development.

Iodine-125 irradiation inhibits invasion of gastric cancer cells by reactivating microRNA-181c expression.

Iodine-125 (125I) seed implantation has been widely used for the treatment of unresectable advanced tumors. However, the molecular mechanisms underlying the tumor-suppressive effects of 125I irradiation have not been fully elucidated. The present study demonstrated that 125I irradiation suppresses cell viability and inhibits cell invasiveness of gastric cancer KATO-III and MKN45 cells. Further mechanistic analysis suggested the involvement of microRNA (miR)-181c in the inhibitory effects induced by 125I irradiation. Methylated DNA immunoprecipitation coupled with quantitative-polymerase chain reaction demonstrated that treatment with 125I irradiation, at the dose of 4 Gy, induced promoter demethylation of the miR-181c gene in KATO-III and MKN45 cells. Following irradiation, the expression of miR-181c was significantly increased, which may be attributed to the demethylation caused by 125I irradiation. In addition, upregulation of miR-181c by administration of miR-181c mimics decreased cell invasion, suggesting the role of miR-181c as a tumor suppressor. More importantly, the tumor-suppressive effects of 125I irradiation were significantly compromised by the introduction of miR-181c inhibitors. Overall, these results reveal that 125I irradiation inhibits invasiveness of gastric cancer cells by reactivating miR-181c at the epigenetic level, thereby providing important molecular evidence for the anticancer effects of 125I irradiation.

[125I seed implantation in sphincter preservation for treatment of low rectal cancer].

OBJECTIVE: To evaluate the effects of (125)I seed implantation in sphincter preservation for treatment of low rectal cancer. METHODS: Seventy-six patients with low rectal cancer were randomly divided into 2 group: group A, 17 males and 13 females, aged 48.5 +/- 2.4, receiving rectostomy and anal sphincter preservation and group B, 24 males and 22 females, aged 49.4 +/- 2.6, receiving modified TME and anal sphincter preservation combined with brachytherapy by (125)I seed implantation. Two to four weeks after operation chemotherapy with 5-FU/CF were performed. Follow-up was carried out 6, 12, 24, and 36 months after operation. RESULTS: The local recurrence rates 6, 12, 24, and 36 months after operation were 0%, 11.1%, 14.3%, and 23% respectively in the group A, and all 0% in the group B (P < 0.05 for the rate 36 months later). The survival rates 6, 12, 24, and 36 months after operation were 100%, 100%, 85.7%, and 76.7% respectively in the group A, and were 100%, 100%, 97.1%, and 93% respectively in the group B (P < 0.05 for the rate 36 months later). The functions of defecation and erection were better in the group B and the symptom of pain was improved better in the group A too (all P < 0.05). CONCLUSIONS: Safe, simple, and effective, surgery with sphincter preservation combined with brachytherapy in low rectal cancer is one of the ideal methods for treatment of low rectal cancer.

[Iodine-125 interstitial brachytherapy for malignant tumor].

OBJECTIVE: To assess the clinical effects of (125)I interstitial brachytherapy for malignant tumors. METHODS: One hundred and twelve patients with malignant tumors of stage II stage and III under went radical resection combined with (125)I intraoperative implantation. Seven days and three month after operation WBC count and immune markers were observed. Blood biochemistry ultrasonography and X-ray were performed to observe recurrence and metastasis of tumors per three months. RESULTS: In the 112 patients, 3 died of tumor recurrence in six months, and others survived with the longest time of 35 months. CONCLUSION: (125)I interstitial brachytherapy for malignant tumor is simple, safe and effective.