Sulforaphane alleviates LPS-induced inflammatory injury in ARPE-19 cells by repressing the PWRN2/NF-kB pathway.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population and its pathogenesis has been associated with inflammatory damage to retinal pigment epithelial (RPE) cells. Here, we explored the ability of sulforaphane to protect ARPE-19 cells from lipopolysaccharide (LPS)-induced inflammatory injury and elucidated the underlying molecular mechanism. METHODS: Cell viability, apoptosis, inflammation, PWRN2 expression, nuclear transcription factor-kappa B (NF-kB) activity, and the interaction between PWRN2 and the IkBa protein were assessed in RPE cells under- or over-expressing PWRN2 that had been treated with LPS and sulforaphane. RESULTS: Overexpression of PWRN2 in LPS-treated cells promoted NF-kB activation by interacting with IkBa, thus reducing cell viability. In contrast, PWRN2 downregulation repressed LPS-induced NF-kB activation and apoptosis in RPE cells. Similarly, sulforaphane downregulated PWRN2 and inhibited NF-kB activation in a concentration-dependent manner. Conversely, PWRN2 overexpression or NF-kB upregulation weakened the anti-inflammatory effects of sulforaphane. CONCLUSION: Our results suggest that sulforaphane protects RPE cells from LPS-induced inflammatory injury by suppressing the PWRN2/NF-kB pathway.

[Clinical features of Kasabach-Merritt syndrome: an analysis of 16 neonates].

OBJECTIVE: To study the clinical features, treatment, and prognosis of neonates with Kasabach-Merritt syndrome (KMS), and to provide a reference for optimizing the diagnosis and treatment of this disease. METHODS: A retrospective analysis was performed for the clinical and follow-up data of 16 neonates with KMS who were admitted to the Anhui Children's Hospital, Anhui Medical University, from January 2016 to December 2020. RESULTS: Of the 16 neonates, there were 13 boys (81%) and 3 girls (19%), with an age of 1 hour to 10 days on admission. Among these neonates, 13 (81%) had cutaneous hemangioma (2 in the head and face, 5 in the trunk, and 6 in the extremities) and 3 (19%) had liver hemangioma. The main clinical manifestations of bleeding tendency and scattered petechiae and ecchymosis were observed in 10 neonates (62%). All the 16 neonates had varying degrees of thrombocytopenia and coagulation disorders. They all received glucocorticoid treatment after admission and 7 (44%) of them had response, among whom 4 experienced recurrence. Among the neonates with no response to glucocorticoid treatment, 3 received sirolimus treatment, among whom 1 had the tumor volume reduced by 58.8% after 4 weeks of treatment, with platelet count and coagulation function returning to normal, while 2 had no significant reduction in tumor volume or significant increase in platelet count and achieved a tumor volume reduced by (43.7±0.4)% after 4 weeks of combined treatment with bleomycin arterial embolization, with platelet count and coagulation function returning to normal. After 4 weeks of bleomycin arterial embolization alone for 4 neonates, tumor volume was reduced by (52.0±3.4)%, and platelet count and coagulation function returned to normal. Blunt and sharp dissection was performed for 2 neonates. The tumor was removed completely during surgery in the 2 neonates, with no infection or recurrence after surgery, and platelet count and coagulation function returned to normal. The postoperative pathological examination showed Kaposiform hemangioendothelioma in 1 out of the 2 neonates. CONCLUSIONS: KMS has characteristic clinical manifestations, histopathological features, and laboratory examination results. The KMS neonates who are not sensitive to glucocorticoids can achieve a good curative effect through arterial embolization and sirolimus treatment.

High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms.

Cherry hemangioma is the most common hemangioma in adult life. Neoplastic and non-neoplastic theories had both been proposed for its pathogenesis, but its nature is still poorly understood. We noted a significant subset of anastomosing hemangiomas and congenital hemangiomas harbored a population of small capillaries surrounded by a perivascular hyaline layer, reminiscent of the vessels seen in cherry hemangioma. Both anastomosing hemangioma and congenital hemangioma harbor recurrent mutations in exon 5 of GNAQ and its paralogues. In this study, we analyzed 68 cherry hemangiomas and 17 cherry hemangioma-like hemangiomas exhibiting additional non-classical features including markedly dilated, cavernous vessels, and/or a deep component extending to the deep dermis. By Sanger sequencing, GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 12, 4, and 32 cherry hemangiomas, respectively, and 5, 3, and 3 cherry hemangioma-like hemangiomas, respectively. MassARRAY analysis detected mutations (including exon 2 GNAQG48V mutations) in additional 8 cherry hemangiomas and 3 cherry hemangioma-like hemangiomas. Overall, the cherry hemangiomas and cherry hemangioma-like hemangiomas had equal GNA mutation rates (82%), and GNA14 and GNAQ mutations were present in approximately half of cherry hemangiomas and cherry hemangioma-like hemangiomas, respectively. All mutations were mutually exclusive. KRASG12V mutation was also detected in one cherry hemangioma-like hemangioma without GNA mutations. In summary, our study demonstrated recurrent GNA14/GNAQ/GNA11 mutations were present in the majority of this very common hemangioma and established its neoplastic nature. Our results also expanded the morphological spectrum of GNA-mutated hemangiomas to include tumors composed of cavernous-like vessels and indicated GNA14 was the most commonly mutated gene in vascular tumors.

GIS assessment of the risk of gene flow from Brassica napus to its wild relatives in China.

Risk of gene flow from canola (Brassica napus) to species of wild relatives was used as an example to evaluate the risk of gene flow of transgenic crops. B. juncea and B. rapa were the most common weedy Brassica species in China, which were both sexually compatible with canola. Data on canola cultivation in China were collected and analyzed using geographic information system (GIS), and the distribution of its wild relatives was predicted by MaxEnt species distribution model. Based on biological and phenological evidence, our results showed that gene flow risk exists in most parts of the country, especially in places with higher richness of wild Brassica species. However, risk in dominant canola cultivation regions is relatively low owing to the reduced distribution density of wild species in these regions. Three regions of higher risk of gene flow had been identified. Risk of gene flow is relatively high in certain areas. China has been assumed to be the original center of B. juncea and B. rapa, and gene flow may lead to negative effects on the conservation of biodiversity of local species. Strategies had been proposed to reduce the possibility of gene flow either by monitoring introgression from crops to wild relatives in the areas of high adoption of the crop or by taking measures to limit the releasing of new crops or varieties in the areas with abundant wild relatives.

[Melanin Synthesis was Affected by Extracts of 22 Kinds Chinese Herbs of Acid Taste: an Experi- mental Study].

OBJECTIVE: To confirm the inhibitory effect of Chinese herbs of acid taste on melanin synthesis. METHODS: Active ingredients of 22 kinds Chinese herbs of acid tastes were extracted by alkali extraction and acid precipitation, alcohol extraction, and water extraction, respectively, which was then dispensed into 25.00, 12.50, and 6.25 g/L suspension. Their effects on activities of tyrosinase were detected using mushroom-tyrosinase-DOPA speed oxidation. Their inhibition rates on activities of tyrosinase were respectively compared with inhibition rates of 1.0, 0.5, and 0.1 mmol/L arbutin. RESULTS: The 22 kinds Chinese herbs of acid taste included Cornus Officinalis, Crataegus pinnatifida, dark plum fruit, Schisandra Chinensis, Chaenomeles sinensis Koehne, Reynoutria japonica Houtt, Achyranthes Bidentata, Sanguisorba officinalis L., Semen Ziziphi Spinosae, Herba Ecliptae, blueberry, immature bitter orange, submature bitter orange, Prunus mume Var, Hovenia acerba Lindl., Fructus Mori, Pomegranate Rind, white paeony root, Rosa laevigata Michx., Portulaca oleracea L, Terminalia chebula Retz, Rhus chinensis Mill. Their alkaline extractions showed inhibition to activities of tyrosinase to different degrees except Herba Ecliptae. Of them, the highest inhibition rate (88.49% ± 9.98%) was got by dark plum fruit at 25 g/L, while the lowest inhibition rate (11.22% ± 3.36%) was got by immature bitter orange at 6.25 g/L. Their alcohol extractions showed inhibition to activities of tyrosinase to different degrees except Herba Ecliptae. Of them, the highest inhibition rate (75.92% ± 5.57%) was got by Hovenia acerba Lindl. at 25 g/L, while the lowest inhibition rate (9.60% ± 1.15%) was got by submature bitter orange at 6.25 g/L. Their water extractions all had inhibition on activities of tyrosinase. Of them, the highest inhibition rate (54.23% ± 3.56%) was got by Fructus Mori at 25 g/L, while the lowest inhibition rate (10.25% ± 1.83%) was got by Semen Ziziphi Spinosae at 6.25 g/L. Compared with 1 mmol/L arbutin water solution, alkaline extractions of dark plum fruit, Schisandra Chinensis, Rhus chinensis Mill., Rosa laevigata Michx., blueberry, Chaenomeles sinensis Koehne, Portulaca oleracea L, Fructus Mori, Achyranthes Bidentata, Pomegranate Rind; alcohol extractions of dark plum fruit, Rhus chinensis Mill., Pomegranate Rind, Hovenia acerba Lindl., Crataegus pinnatifida, Achyranthes Bidentata; water extractions of Chaenomeles sinensis Koehne, blueberry, and Fructus Mori at 25 g/L got obviously higher inhibition rates (P < 0.05, P < 0.01). Compared with 0.5 mmol/L arbutin water solution, alcohol extraction of Chaenomeles sinensis Koehne and alcohol extraction of dark plum fruit at 12.5 g/L got obviously higher inhibition rates (P < 0.05, P < 0.01). CONCLUSION: Chinese herbs of acid taste could inhibit melanin synthesis, and its mechanism was related to inhibiting activities of tyrosinase.

The effects of Photofrin-mediated photodynamic therapy on the modulation of EGFR in esophageal squamous cell carcinoma cells.

Photodynamic therapy (PDT) has been demonstrated to be an effective minimally invasive treatment modality for early esophageal cancer. However, the molecular action in esophageal cancer during PDT is hardly known. EGFR has been known to downregulate in various cancer cells during PDT. In this study, we investigated the effects of Photofrin-mediated PDT on cell death and expression of EGFR in CE48T/VGH (CE48T) esophageal squamous cell carcinoma cells. We found that the photosensitizer Photofrin in the absence of light exposure can downregulate the expression of EGFR at both transcription and translation levels. Higher concentrations of Photofrin results in cytotoxicity whereas lower doses of Photofrin inhibit EGFR expression under dark control without inducing significant cell death. This Photofrin-associated inhibition of EGFR was repeated in lung cancer, cervical cancer, and glioblastoma cells. Another esophageal squamous cell carcinoma cell line CE81T/VGH (CE81T) was found to be resistant to Photofrin-induced inhibition of EGFR as well as to Photofrin-mediated dark toxicity compared with CE48T. The resistance to the cytotoxicity in CE81T cells became insignificant when the Photofrin-treated cells were further irradiated by red light (Photofrin-PDT). We suggest Photofrin modulates the expression of EGFR in cancer cells. However, efficient cell death still requires the combination of Photofrin and light irradiation in esophageal squamous cell carcinoma cells.

Clinical Application of a Graphene Oxide-Based Surface Plasmon Resonance Biosensor to Measure First-Trimester Serum Pregnancy-Associated Plasma Protein-A/A2 Ratio to Predict Preeclampsia.

Background: Preeclampsia, a major cause of adverse pregnancy outcomes, involves metalloproteinases pregnancy-associated plasma protein (PAPP)-A and PAPP-A2 from placental trophoblasts. The graphene oxide (GO)-based surface plasmon resonance (SPR) biosensor has higher sensitivity, affinity, and selective ability than the traditional SPR biosensor. The aim of this study was to explore the feasibility of measuring first-trimester serum PAPP-A/PAPP-A2 ratio as a novel predictor of preeclampsia using the GO-SPR biosensor. Methods: This prospective case-control study of pregnant women was conducted at MacKay Memorial Hospital, Taipei, Taiwan between January 2018 and June 2020. The SPR angle shifts of first-trimester serum PAPP-A, PAPP-A2, and PAPP-A/PAPP-A2 ratio measured using the GO-SPR biosensor were compared between preeclampsia and control groups. Results: Serum samples from 185 pregnant women were collected, of whom 30 had preeclampsia (5 early-onset; 25 late-onset). The response time between the antibody-antigen association and dissociation only took about 200 seconds. The SPR angle shift of PAPP-A in the preeclampsia group was significantly smaller than that in the control group (median (interquartile range): 5.33 (4.55) versus 6.89 (4.10) millidegrees (mDeg), P = 0.008). Conversely, the SPR angle shift of PAPP-A2 in the preeclampsia group was significantly larger than that in the control group (5.70 (3.81) versus 3.63 (2.38) mDeg, P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict all preeclampsia of ≤ 0.76, with an area under the ROC curve (AUC) of 0.79 (95% CI 0.73-0.85, P < 0.001). Sub-group analysis revealed a cut-off PAPP-A/PAPP-A2 ratio to predict early-onset preeclampsia of ≤ 0.53 (AUC 0.99, 95% CI 0.96-1.00, P < 0.001), and ≤ 0.73 to predict late-onset preeclampsia (AUC 0.75, 95% CI 0.68-0.81, P < 0.001). Conclusion: Measuring first-trimester serum PAPP-A/PAPP-A2 ratio using the GO-SPR biosensor could be a valuable method for early prediction of preeclampsia.

Maternal dominance contributes to subgenome differentiation in allopolyploid fishes.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed 'subgenome dominance' remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

Downregulation of NADPH-cytochrome P450 reductase via RNA interference increases the susceptibility of Acyrthosiphon pisum to desiccation and insecticides.

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is involved in the metabolism of endogenous and exogenous substances, and detoxification of insecticides. RNA interference (RNAi) of CPR in certain insects causes developmental defects and enhanced susceptibility to insecticides. However, the CPR of Acyrthosiphon pisum has not been characterized, and its function is still not understood. In this study, we investigated the biochemical functions of A. pisum CPR (ApCPR). ApCPR was found to be transcribed in all developmental stages and was abundant in the embryo stage, and in the gut, head, and abdominal cuticle. After optimizing the dose and silencing duration of RNAi for downregulating ApCPR, we found that ApCPR suppression resulted in a significant decrease in the production of cuticular and internal hydrocarbon contents, and of cuticular waxy coatings. Deficiency in cuticular hydrocarbons (CHCs) decreased the survival rate of A. pisum under desiccation stress and increased its susceptibility to contact insecticides. Moreover, desiccation stress induced a significant increase in ApCPR mRNA levels. We further confirmed that ApCPR participates in CHC production. These results indicate that ApCPR modulates CHC production, desiccation tolerance, and insecticide susceptibility in A. pisum, and presents a novel target for pest control.

Polymorphism in epidermal growth factor receptor intron 1 predicts prognosis of patients with esophageal cancer after chemoradiation and surgery.

BACKGROUND: The EGFR gene has been demonstrated to be an important factor influencing treatment response for various cancers, and its expression has been shown to be modified by the polymorphic CA repeat length at the 5'-regulatory sequence in intron 1. We investigated whether this EGFR polymorphism is associated with prognosis in patients with esophageal cancer after concurrent chemoradiotherapy (CCRT) and esophagectomy. METHODS: A cohort of 148 patients with esophageal cancer received cisplatin-based CCRT (concurrently combined with 40 Gy irradiation) and subsequent esophagectomy. Their EGFR genotypes were determined by polymerase chain reaction from leukocyte DNA, which was obtained before treatment and was correlated with patient survival. RESULTS: Patients with the homozygous short allele (<20 CA) of the EGFR gene in intron 1 were more likely to have a shorter duration of survival after CCRT and surgery than those with the homozygous long allele [adjusted hazard ratio (HR) (95% confidence interval [CI]) of death: 1.88 (1.02-3.49); P = 0.045]. This unfavorable prognostic effect of EGFR homozygous short CA repeat was mainly manifested in patients with good response to CCRT [adjusted HR (95% CI) of death 3.40 (1.06-10.89); P = 0.039]; it was less evident in those with poor response to CCRT [adjusted HR (95% CI) 1.40 (0.65-3.02); P = 0.384]. CONCLUSIONS: The EGFR CA repeat genetic polymorphism may act as a valuable molecular predictor of clinical outcome of esophageal cancer after CCRT and esophagectomy, especially in those with good response to CCRT.

Liver Failure of Wilson's Disease With Manifestations Similar to Porphyria and Uncommon ATP7B Gene Mutation: A Case Report and Literature Review.

Background: Wilson's disease (WD) is a rare condition; its diagnosis is challenging owing to a wide spectrum of ATP7B genotypes and variable clinical phenotypes, along with environmental factors. Few cases of WD with presentation of skin lesions and acute neurovisceral symptoms have been reported in the literature. To our knowledge, this is the first reported case of WD with an uncommon ATP7B gene mutation and rare symptoms of photosensitivity, sensation abnormality, and skin eruption occurring in a 19-year-old woman. Case presentation: We report the case of a 19-year-old woman with WD presenting with liver failure, skin manifestations, and acute neurovisceral symptoms.The rare mutation in intron 1 of ATP7B (c.51+2T > G) was further confirmed by gene sequencing. The patients' symptoms improved after administration of penicillamine and zinc therapy combined with plasma exchange. She received long-term penicillamine treatment, and her liver function was within the normal range at 1 year after discharge. However, she underwent liver transplantation at 1.5 years after discharge. Conclusions: We present a case of WD with a novel ATP7B gene mutation that may serve as a reference to generalists and specialists in hepatology or neurology of the rare clinical characteristics of WD, to prevent misdiagnosis and aid in the early diagnosis and treatment of the condition.

Immunoassay-Amplified Responses Using a Functionalized MoS2-Based SPR Biosensor to Detect PAPP-A2 in Maternal Serum Samples to Screen for Fetal Down's Syndrome.

BACKGROUND: Due to educational, social and economic reasons, more and more women are delaying childbirth. However, advanced maternal age is associated with several adverse pregnancy outcomes, and in particular a high risk of Down's syndrome (DS). Hence, it is increasingly important to be able to detect fetal Down's syndrome (FDS). METHODS: We developed an effective, highly sensitive, surface plasmon resonance (SPR) biosensor with biochemically amplified responses using carboxyl-molybdenum disulfide (MoS2) film. The use of carboxylic acid as a surface modifier of MoS2 promoted dispersion and formed specific three-dimensional coordination sites. The carboxylic acid immobilized unmodified antibodies in a way that enhanced the bioaffinity of MoS2 and preserved biorecognition properties of the SPR sensor surface. Complete antigen pregnancy-associated plasma protein-A2 (PAPP-A2) conjugated with the carboxyl-MoS2-modified gold chip to amplify the signal and improve detection sensitivity. This heterostructure interface had a high work function, and thus improved the efficiency of the electric field energy of the surface plasmon. These results provide evidence that the interface electric field improved performance of the SPR biosensor. RESULTS: The carboxyl-MoS2-based SPR biosensor was used successfully to evaluate PAPP-A2 level for fetal Down's syndrome screening in maternal serum samples. The detection limit was 0.05 pg/mL, and the linear working range was 0.1 to 1100 pg/mL. The women with an SPR angle >46.57 m° were more closely associated with fetal Down's syndrome. Once optimized for serum Down's syndrome screening, an average recovery of 95.2% and relative standard deviation of 8.5% were obtained. Our findings suggest that carboxyl-MoS2-based SPR technology may have advantages over conventional ELISA in certain situations. CONCLUSION: Carboxyl-MoS2-based SPR biosensors can be used as a new diagnostic technology to respond to the increasing need for fetal Down's syndrome screening in maternal serum samples. Our results demonstrated that the carboxyl-MoS2-based SPR biosensor was capable of determining PAPP-A2 levels with acceptable accuracy and recovery. We hope that this technology will be investigated in diverse clinical trials and in real case applications for screening and early diagnosis in the future.

Exploring Graphene and MoS2 Chips Based Surface Plasmon Resonance Biosensors for Diagnostic Applications.

Until now, two-dimensional (2D) nanomaterials have been widely studied and applied in the biosensor field. Some of the advantages offered by these 2D materials include large specific surface area, high conductivity, and easy surface modification. This review discusses the use of 2D material in surface plasmon resonance (SPR) biosensor for diagnostic applications. Two-dimensional material reviewed includes graphene and molybdenum disulfide (MoS2). The discussion begins with a brief introduction to the general principles of the SPR biosensor. The discussion continues by explaining the properties and characteristics of each material and its effect on the performance of the SPR biosensor, in particular its sensitivity. This review concludes with some recent applications of graphene- and MoS2-based SPR biosensor in diagnostic applications.

Clinical Application for Screening Down's Syndrome by Using Carboxylated Graphene Oxide-Based Surface Plasmon Resonance Aptasensors.

BACKGROUND: Advanced medical detection technology requires high sensitivity and accuracy to increase the disease detection rate. We showed that carboxyl-functionalized graphene oxide (carboxyl-GO) biosensing materials are capable of accurate detection. METHODS: We developed a carboxylated GO-based surface plasmon resonance (SPR) aptasensor suitable for screening Down's syndrome in clinical serum. This biosensing material could rapidly and accurately detect hCG protein with a low concentration to identify fetal Down's syndrome. The developed carboxyl-GO-based SPR aptasensor showed excellent sensitivity and limit of detection without the use of antibodies and without any specific preference. RESULTS: hCG protein detection limits of 1 pM in buffer samples and 1.9 pM in clinical serum samples were achieved. The results showed that the carboxyl-GO-based chip could detect hCG well below the normal physiological level of serum protein (5.0 mIU/mL). High affinity, sensitivity, and better detection limit were obtained in the range of 1.9 pM to 135 pM. The results showed a 5k-fold dilution factor, and that an SPR angle shift of more than 20 millidegrees (mo) was associated with a significant risk of fetal Down's syndrome compared to normal pregnant women. The results clearly showed that the detection of hCG protein in serum samples from pregnant women at 12-19 weeks could be used to screen Down's syndrome with high selectivity and sensitivity. CONCLUSION: Our findings suggest the potential application of carboxyl-GO film in proof-of-concept studies for serum assays as a new type of SPR material. In addition, peptide and carboxyl-GO films may be conducive to the development of future point of care testing and rapid diagnostic devices for other diseases such as cancer.

Thrombotic Hemangioma With Organizing/Anastomosing Features: Expanding the Spectrum of GNA-mutated Hemangiomas With a Predilection for the Skin of the Lower Abdominal Regions.

In this study, we aimed to present the clinicopathologic and molecular features of a distinct group of hemangioma with GNA mutations that exhibited prominent thrombosis and organization changes with florid intravascular endothelial cell proliferation that we provisionally termed "thrombotic hemangioma with organizing/anastomosing features." Twenty-six cases were included. No sex predilection was seen (male:female=13:13). Patients' age ranged from 17 to 89 years (median: 51 y). All but 1 occurred in the skin whereas the remaining tumor involved the neck soft tissue. Remarkably, the majority (18) occurred in the lower abdominal/inguinal regions. Histologically, thrombotic hemangioma with organizing/anastomosing features were circumscribed tumors composed of variably sized and congested thin-walled vessels. The most striking features were prominent thrombosis and organization with florid intravascular endothelial cell proliferation. The proliferating endothelial cells exhibit a streaming pattern with focal anastomosing-like feature resembling anastomosing hemangioma. The stroma was sclerotic or hyalinized but could also be myxoid/edematous. Other features included vessels with nuclear hobnailing and perivascular hyalinization, cherry hemangioma-like component, cavernous-like or sinusoidal hemangioma-like areas, Masson hemangioma-like feature, and spindle cell fascicular pattern. Mitotic activity was usually low and nuclei were bland but 2 tumors exhibited moderate nuclear atypia and higher mitotic activity. Extramedullary hematopoiesis and hyaline globules were not identified. Genetically, by Sanger sequencing and MassARRAY analysis, mutually exclusive GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 15, 5, and 2 tumors, respectively, with a combined mutation rate of 85% (22/26). In conclusion, we described a distinct group of hemangioma and expanded the clinicopathologic features of GNA-mutated hemangiomas.

GNA11 joins GNAQ and GNA14 as a recurrently mutated gene in anastomosing hemangioma.

Anastomosing hemangioma (AH) is a distinct benign vascular tumor that may be histologically confused with an angiosarcoma. Recently, recurrent GNAQ and GNA14 mutations were identified in AH. GNA11, another paralogue of GNAQ and the one that shows the highest degree of homology to GNAQ, has not yet been found to be mutated in AH. In this study, we investigated the clinicopathological and molecular features of 26 AHs. By Sanger sequencing and MassARRAY analysis, mutually exclusive mutations in exon 5 of GNAQ, GNA11, and GNA14 were identified in 10, 5, and 5 tumors, respectively, of the 22 investigated tumors, with an overall mutation rate of 91%. No notable differences in the clinicopathological features were observed between GNAQ-, GNA11-, or GNA14-mutated tumors. Our results implicated GNA11 mutations, as well as previously known mutations of its paralogues GNAQ and GNA14, as essential drivers in the pathogenesis of AH.

Up-Regulated AKR1C2 is correlated with favorable prognosis in thyroid carcinoma.

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

Novel strategy of stents in thyroid mass: a case series report of managing severely dyspneic patients.

BACKGROUND: Tracheal and bronchial stenosis is a life-threatening condition causing difficulty in breathing and even severe respiratory distress. The silicone tracheobronchial stents were placed using the rigid bronchoscopy into the trachea of severe dyspneic patients and they exhibited symptomatic improvement as well as a rise in the saturation of oxygen. The bronchial stents were applicable to many extensive malignant airway stenosis patients, such as those with esophageal cancer, lung cancer, and laryngeal cancer. But the effectiveness of bronchial stents for thyroid cancer is not certain. CASE PRESENTATION: Here, we report 3 emergency patients with a thyroid mass referred to our hospital because of grade 4 dyspnea according to the American Thoracic Society shortness of breath guidelines. The main clinical symptoms were severe dyspnea and stridor. The radiographic examination and tomographic examination showed the narrowing and displacement of the trachea. To the best of our knowledge, ideal airway management for the massive thyroid mass was considered to be temporary tracheobronchial stent placement pre-operation. CONCLUSION: In our study, we applied the tracheobronchial stent to massive thyroid mass patients with dyspnea and aimed to not only improve preoperative airway obstruction but also to protect the potential airway collapse from post-operative tracheomalacia following extubation. We found that application of tracheobronchial stents may provide a new strategy to dyspneic patients with huge thyroid mass.

MLF1IP promotes cells proliferation and apoptosis by regulating CyclinD1 in breast cancer.

Breast cancer is the most frequently diagnosed cancer and the leading causes of cancer death among females in worldwide. It is urgent to develop novel biomarkers to improve risk stratification and optimize therapy choice. In our previous study, we firstly found that MLF1IP was upregulated in breast cancer tissue compared with adjacent normal tissue and patients with high MLF1IP expression had significantly lower overall survival. However, the biological function and cellular mechanisms of MLF1IP in breast cancer is still need to be elucidated. Here, we further investigated the role of MLF1IP in breast cancer by in vivo experiments. Our results showed that the expression level of MLF1IP was associated with lymph nodes metastasis and tumor size in clinical characteristic features. By biological function experiment, we found MLF1IP is correlated with cell proliferation and apoptosis and arrest cell cycle G1 through regulating Cyclin D1. Taken together, our findings suggested that MLF1IP could contribute to the oncogenic potential of breast cancer. To the best of our knowledge, it was firstly reported that MLF1IP was involved in breast cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment.

Risk factors for hypocalcemia and hypoparathyroidism following thyroidectomy: a retrospective Chinese population study.

BACKGROUND: Hypocalcemia is one of the most common postoperative complications following thyroid surgery in clinical practice. The occurrence of hypocalcemia is mainly attributed to hypoparathyroidism when parathyroid glands are devascularized, injured, or dissected during the surgery. The aim of this study was to analyze the risk factors for hypocalcemia and hypoparathyroidism following thyroidectomy. PATIENTS AND METHODS: A total of 278 patients who underwent thyroid surgery were analyzed retrospectively. Univariate analysis and multivariable logistic regression were performed to discover the risk factors for hypocalcemia and hypoparathyroidism. RESULTS: Postoperative hypocalcemia occurred in 76 (27.3%) patients and hypoparathyroidism occurred in 42 (15.1%) patients. Seven factors were significantly related to the presence of postoperative hypocalcemia, namely, age (P=0.049), gender (P=0.015), lateral lymph node dissection (P=0.017), operation type (P<0.001), preoperative parathyroid hormone (PTH) level (P=0.035), operation time (P=0.001), and applying carbon nanoparticles (CNs; P=0.007). Our result revealed that gender (P=0.014), lateral lymph node dissection (P=0.038), operation type (P<0.001), operative time (P<0.001), and applying CNs (P=0.001) had a significant correlation with postoperative hypoparathyroidism. CONCLUSION: These findings were crucial for guiding surgeons to prevent the occurrence of hypocalcemia and hypoparathyroidism.