Complete Response to Immunotherapy Combined With Chemotherapy in a Patient With Gynecological Mixed Cancer Mainly Composed of Small Cell Neuroendocrine Carcinoma With High Tumor Mutational Burden: A Case Report.

Small cell neuroendocrine carcinoma (SCNEC) is rare in the gynecologic tract, which has high invasive and metastatic ability. Due to the aggressive behavior and lack of treatment, patients have an extremely poor prognosis. Here we report a 66-year-old female diagnosed with SCNEC in the gynecologic tract, mixed with endometrioid adenocarcinoma, squamous cell, and adenosquamous carcinoma. A tumor mutational burden of 13.14 Muts/Mb was detected by next-generation sequencing. The patient underwent a palliative operation of total hysterectomy with bilateral adnexectomy but suffered from disease progression in a short time after the operation. Chemotherapy (paclitaxel + carboplatin) combined with immunotherapy (toripalimab) was conducted every 3 weeks, achieving a partial response after 2 cycles of treatment. After 5 cycles of combined treatment, the patient consolidated with monotherapy of toripalimab for about half a year and achieved a complete response. Until December 2021, the patient has achieved 27 months of progression-free survival and maintains a continued complete response. This case is presented due to the rare combination of pathological types and durable response to treatment especially immunotherapy, suggesting the potential value of immunotherapy in SCNEC of the gynecologic tract.

Phosphate mining activities affect crop rhizosphere fungal communities.

Phosphate mining releases heavy metals into the surrounding environment. In this study, the effects of phosphate mining on rhizosphere soil fungi in surrounding crops, including Lactuca sativa var. angustata, Glycine max (L.) Merr., and Triticum aestivum L., were assessed. Phosphate mining significantly reduced the crop rhizosphere fungal diversity (P < 0.05). The relative abundances of Fusarium and Epicoccum increased in mining rhizosphere soil compared with the baseline. Beta diversity analysis indicated that phosphate mining led to the differentiation of fungal community structure in plant rhizospheres. Guild analysis indicated that different plant rhizosphere fungi developed various guilds in response to phosphate mining stress. Nine fungi were isolated from soil samples, with solubilization index values ranging from 1.1 to 2.5. Two efficient phosphate solubilizers, Epicoccum nigrum and Fusarium verticillioides, were enriched in phosphate mining rhizosphere soil samples. The dissolution kinetics of inorganic phosphorus and alkaline phosphatase activity assay showed strong phosphorus dissolution ability of the isolated fungi. Penicillium aculeatum, Trichoderma harzianum, Chaetomium globosum, and F. verticillioides showed strong tolerance to multiple heavy metals. This study furthers our understanding of how rhizosphere fungal ecology is affected by phosphate mining and provides important resources for the remediation of phosphate mining soil pollution.

Characterization of the complete mitochondrial genome of Dioszegia changbaiensis (Tremellales: Bulleribasidiaceae) with phylogenetic implications.

In this study, the complete mitochondrial genome of Dioszegia changbaiensis we sequenced and assembled by the next-generation sequencing. The complete mitochondrial genome of Dioszegia changbaiensis contained 22 protein-coding genes (PCG), two ribosomal RNA (rRNA) genes, and 22 transfer RNA (tRNA) genes. The total length of the Dioszegia changbaiensis mitochondrial genome is 34,853 bp, and the GC content of the mitochondrial genome is 41.88%. Phylogenetic analysis based on a combined mitochondrial gene dataset indicated that the mitochondrial genome of Dioszegia changbaiensis exhibited a close relationship with that of Hannaella oryzae.

A review on high velocity compaction mechanism of powder metallurgy.

High Velocity Compaction (HVC) is a key technology to realize the performance of powder metallurgy parts "three high and one low" (high density, high precision, high performance, and low cost). The main purpose of this paper is to summarize the research results at home and abroad on the forming mechanism, forming influencing factors and theoretical basis of high velocity compaction. This paper analyzes and summarizes the literature and monographs at home and abroad through literature research methods to obtain the research results of high velocity powder metallurgy compaction, so as to fully and correctly understand the research progress, development trends and application prospects of high velocity compaction. This paper expounds the technical characteristics, advantages and limitations of high velocity compaction, and analyzes and looks forward to its development trend, application prospect and expansion field, So as to provide reference and reference for the future research and application direction of high velocity compaction technology.

Acute necrotising pancreatitis: measurements of necrosis volume and mean CT attenuation help early prediction of organ failure and need for intervention.

OBJECTIVES: This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP). METHODS: A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis. RESULTS: There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN. CONCLUSIONS: The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention. KEY POINTS: • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis.

CT and MRI characteristic findings of sporadic renal hemangioblastoma: Two case reports.

RATIONALE: Hemangioblastomas in the kidney are rare. Although a few cases of renal hemangioblastoma (RH) have been reported, the content of these articles mainly focused on clinical and pathological research, with minimal descriptions of radiologic findings. Moreover, there are no descriptions of magnetic resonance imaging (MRI) with enhancement of this condition. Herein, we report 2 cases of RH with computed tomography (CT) and MRI findings. PATIENT CONCERNS: Two patients presented to our institution because of dull pain in the left abdomen, and a mass in the left kidney was found by ultrasound examination in each case. The patient had no special family history. Physical examination revealed no obvious tenderness or percussion pain in the renal and ureteral walking areas, and there was no obvious mass. Routine blood and urine tests were normal, and the serum tumor markers were negative. No obvious lesions were found on imaging of the other body parts. DIAGNOSIS: Similar radiologic findings were observed in both cases and mimicked those of cavernous hemangiomas of the liver, including peripheral nodular enhancement in the corticomedullary phase, progressive centripetal enhancement in the nephrographic and delayed phases, and occasional complete "filling in" in the delayed phase. We made a radiologic diagnosis of renal clear cell carcinoma for patient 1 and suspected renal clear cell carcinoma for patient 2, but the pathological results showed RH. INTERVENTIONS: Given the suspicion of renal cell carcinoma, both patients underwent partial nephrectomy. OUTCOME: The recovery of the two patients was uneventful, and there was no evidence of local recurrence or metastasis many years after surgery. LESSONS: RH is a rare benign tumor that can be easily misdiagnosed as clear cell carcinoma. Characteristic CT and MRI manifestations may improve preoperative diagnostic accuracy to avoid surgery or indicate nephron-sparing surgery.

Magnetic resonance colonography with intestine-absorbable nanoparticle contrast agents in evaluation of colorectal inflammation.

OBJECTIVES: To develop a nanoparticle-based MRI protocol based on transrectal administration of intestine-absorbable nanoparticle contrast agents to evaluate ulcerative colitis (UC). METHODS: Solid lipid nanoparticles (SLNs) were synthesized by loading gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine-fluorescein isothiocyanate to produce Gd-FITC-SLNs as T1 contrast agents. Twenty mice with acute UC were divided into four groups: enema with Gd-FITC-SLNs, intravenous injection of Gd-FITC-SLNs, enema with Gd-DTPA, and intravenous injection of Gd-DTPA. Five mice with chronic UC and five mice without UC underwent enema with Gd-FITC-SLNs. Axial T1- and T2-weighted MR images were obtained before and 20, 40, 60, 80,100, and 120 min after enema or intravenous injection of the contrast agent. The signal-to-noise ratios (SNRs) of the colorectal wall were measured in both groups. The MRI findings were correlated with subsequent histological confirmation. RESULTS: At 20 min after enema with Gd-FITC-SLNs, MRI showed the following contrast enhancement pattern: acute UC > normal intestinal wall > chronic UC. A continuous enhancement effect was observed in mice with acute UC, whereas a slight continuous enhancement of the colorectal wall was observed in mice with chronic UC. The normal intestinal wall rapidly metabolized the contrast agent, and the enhancement decreased on sequential scans. There was no significant difference between the SNRs of the intestinal wall at 20 min after intravenous Gd-DTPA and transrectal Gd-FITC-SLN administration. CONCLUSIONS: Enema with Gd-FITC-SLNs may be helpful for the diagnosis and differential diagnosis of acute and chronic UC and can confer the same or better results than with intravenous Gd-DTPA. KEY POINTS: • Enema with Gd-FITC-SLNs may be helpful for the diagnosis and differential diagnosis of acute and chronic UC. • Enema with Gd-FITC-SLNs can achieve the same or better result than that with intravenous Gd-DTPA. • SLN-based MR colonography enhances the colorectal wall inflammation, based on the colonic absorption of the nanoparticle contrast agents.

Characterization of the complete mitochondrial genome of Sterigmatomyces hyphaenes (Agaricostilbales: Agaricostilbaceae) and implications for its phylogeny.

In this study, the complete mitochondrial genome of Sterigmatomyces hyphaenes was sequenced by the next-generation sequencing. The complete mitochondrial genome of S. hyphaenes contained 17 protein-coding genes (PCG), 2 ribosomal RNA (rRNA) genes, and 23 transfer RNA (tRNA) genes. The total size of the S. hyphaenes mitochondrial genome is 26,198 bp, and the GC content of the mitochondrial genome is 42.08%. Phylogenetic analysis based on the combined mitochondrial gene dataset indicated that the mitochondrial genome of S. hyphaenes exhibited a close relationship with that of Rhodotorula mucilaginosa.

Biochemical and genetic basis of cadmium biosorption by Enterobacter ludwigii LY6, isolated from industrial contaminated soil.

In this study, a cadmium-tolerant bacterium, Enterobacter ludwigii LY6, was isolated from cadmium-contaminated soil in Shifang, Sichuan province, China. The cadmium chloride removal rate of the strain LY6 with a treatment of 100 mg/L cadmium chloride reached 56.0%. Scanning electron microscopy showed that exopolysaccharides (EPS) might be the main means of cadmium adsorption by the strain. X-ray powder diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) analyses indicated that cadmium sulfide nanoparticles formed on the surface of bacteria cultured in a medium containing 100 mg/L cadmium chloride. In addition, the expression of several genes increased with the increase of the cadmium concentration in the medium, including the multiple antibiotic resistance proteins marA and marR, and the cold shock protein CspA. GO functions, such as the redox activity, respiratory chain and transport functions, and KEGG pathways involved in "bacterial chemotaxis" and "terpenoid backbone biosynthesis" were found to be closely related to bacterial cadmium tolerance and biosorption. This is the first report that E. ludwigii can reduce sulfate to form cadmium sulfide nanoparticles under high concentration cadmium exposure. The genes related to cadmium tolerance identified in this study lay a foundation for the genetic breeding of cadmium-tolerant strains.

Establishment and Characterization of Two Novel Cholangiocarcinoma Cell Lines.

BACKGROUND: Cholangiocarcinoma (CCA) is a rare, aggressive and highly lethal tumor. The disease is very difficult to diagnose and multi-modality treatments are ineffective. To improve our understanding of the biological characteristics of CCA, and facilitate the identification of valid treatments, an in-depth characterization of two novel Chinese patient-derived primary CCA cell lines was performed. METHODS: Two CCA cell lines were developed and labelled ZJU-0826 and -1125. The two cell lines were characterized with respect to phenotypic, molecular, biomarker, functional and histological properties. RESULTS: Two novel cell lines were cultured for 2 years, and maintained for more than 100 passages. They retained their typical biliary epithelial morphology and ultrastructure. The population doubling times of ZJU-0826, and -1125 were 63.84 h and 44.73 h, respectively. The cells exhibited near-triploid karyotypes with complex structural aberrations. ZJU-1125 cells had mutations in TP53 exons. Short tandem repeats genotyping confirmed the human origin and difference between lines. An immunophenotype analysis showed that ZJU-0826 is positive for CD44, CD29, Pdx1, CD236, FoxA1, FoxA2, and Nanog, and ZJU-1125 positive for CD44, CD29, CD133, Pdx1, FoxA1, FoxA2, and Nanog. ZJU-1125 had greater invasion ability in vitro and tumorigenicity than those of ZJU-0826. CONCLUSIONS: Our results confirm the validity of the ZJU-0826 and -1125 as representative models for the elucidation of the molecular pathogenesis of perihilar CCA, and intrahepatic CCA in both in vitro and in vivo studies, respectively.

A phase II study of biweekly oxaliplatin plus S-1 combination chemotherapy as a first-line treatment for patients with metastatic or advanced gastric cancer in China.

Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m, 1.25-1.5 m, or >1.5 m respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37-5.36 months) and 10.3 months (95% CI, 8.88-11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.

Characterization and comparison of the mitochondrial genomes from two Lyophyllum fungal species and insights into phylogeny of Agaricomycetes.

Lyophyllum decastes and Lyophyllum shimeji are the two primary species within the L. decastes complex, and they differ considerably in their nutritional lifestyles and preferred growth environments. However, differences in their mitogenomes have not yet been investigated. In this study, the mitogenomes of the two species were sequenced by next-generation sequencing technology, successfully assembled, and compared. The two mitogenomes of L. decastes and L. shimeji comprised circular DNA molecules of sizes 50,643 bp and 73,678 bp, respectively. The lengths and base compositions of their core protein coding genes (PCGs) and tRNA genes varied considerably between the two mitogenomes. Further, gene collinearity analysis indicated a large-scale gene rearrangement between the two mitogenomes. Of the 15 core PCGs, the genetic distance of the atp9 gene was the smallest between the two species, indicating that this gene was highly conserved in the two Lyophyllum species. Phylogenetic analysis based on a combined mitochondrial gene dataset resulted in a well-supported topology, wherein the two Lyophyllum species were most closely related to Tricholoma matsutake. This study represents the first report of mitogenomes for the Lyophyllum genus. As such, the results will provide a basis for understanding the differentiation and evolution of mitogenomes in the Lyophyllum genus.

Characterization and comparative analysis of six complete mitochondrial genomes from ectomycorrhizal fungi of the Lactarius genus and phylogenetic analysis of the Agaricomycetes.

Lactarius is one of the most prominent genera of mushroom-forming fungi in the world. In the present study, complete mitochondrial genomes (mitogenomes) from six Lactarius species were sequenced and assembled. The six mitogenomes were all composed of circular DNA molecules, with total lengths ranging from 38,445 bp to 60,843 bp. The GC contents, GC skews, and AT skews of the mitogenomes varied among the six species. Mitogenomic synteny analysis revealed the presence of gene rearrangements among the mitogenomes. Among the 15 core protein coding genes (PCGs) within the mitogenomes, nad4L exhibited the least genetic distance among species, indicating a high degree of conservation. In addition, the Ka/Ks values for all 15 core PCGs were <1, suggesting that they were subject to purifying selection. Comparative analyses indicated that the increase of intron numbers and sizes contributed to the expansion of mitogenomes in Lactarius. Phylogenetic analyses based on three combined gene datasets yielded identical and well-supported (BPP ≥ 0.83) topologies, dividing the six Lactarius species into two groups. This study provides the first report of mitogenomes from Lactarius and promotes further understanding of the genetics, evolution, and phylogenetic relationships of this important ectomycorrhizal fungal genus.

The first complete mitochondrial genome from the family Hygrophoraceae (Hygrophorus russula) by next-generation sequencing and phylogenetic implications.

Hygrophorus russula (Schaeff.) Kauffman is an edible ectomycorrhizal fungus that is widely distributed in the world. In this study, the mitogenome of H. russula was sequenced and assembled. The mitogenome of H. russula is composed of circular DNA molecules, with a total size of 55,769 bp. Further analysis indicated that the frequent use of A and T in codons contributes to the high AT content (80.87%) in the H. russula mitogenome. Comparative analysis indicated that the length and base composition of the core protein-encoding genes, and the number of tRNA genes in the H. russula mitogenome varied from that of other Agaricales mitogenomes. Gene arrangement analysis revealed a novel gene order in the H. russula mitogenome. In addition, the expansion of the mitogenome in Agaricales was found to be closely related to the increase in the number of introns. Phylogenetic analysis of the combined mitochondrial gene set showed strong support for tree topologies, and H. russula was determined to be relatively distant from other Agaricales species. This study is the first report on the mitogenome of a member of genus Hygrophorus as well as family Hygrophoraceae, which improves our understanding of mitochondrial differentiation and evolution in the important ectomycorrhizal fungi Hygrophorus species.

State-of-the-art on the technique of dispersive liquid-liquid microextraction.

Dispersive liquid-liquid microextraction is a new sample pretreatment technology based on traditional liquid liquid extraction. In this paper, the application of low-toxicity extractants such as low-density extractants, auxiliary extractants, stripping agents and ionic liquids in this technology and the extraction modes such as solvent de-emulsification, suspension extractant curing, auxiliary extraction, back extraction, and ionic liquid-dispersion liquid microextraction, are summarized. In addition, the synergism of this technique with other sample preparation techniques, such as liquid-liquid extraction, solid-phase extraction, solid-phase microextraction, dispersive solid phase extraction, matrix solid-phase dispersion extraction, supercritical fluid extraction and ultrasound-assisted dispersive liquid-liquid microextraction is discussed.

Characterization and comparative mitogenomic analysis of six newly sequenced mitochondrial genomes from ectomycorrhizal fungi (Russula) and phylogenetic analysis of the Agaricomycetes.

In this study, the mitochondrial genomes of six Russula species were sequenced using next generation sequencing. The six mitogenomes were all composed of circular DNA molecules, with lengths ranging from 40,961 bp to 69,423 bp. The length and number of protein coding genes (PCGs), GC content, AT skew, and GC skew varied among the six mitogenomes. The increased number and total size of introns likely contributed to the size expansion of mitogenomes in some Russula species. Gene synteny analysis revealed some gene rearrangements among the six mitochondrial genomes. The nad4L gene had the lowest K2P genetic distance of the 15 core PCGs among the six Russula species, indicating that this gene was highly conserved. The Ka/Ks values for all 15 core PCGs were <1, suggesting that they were all subject to purifying selection. Phylogenetic analyses based on two gene datasets (15 core PCGs, and 15 core PCGs + rnl + rns) recovered identical and well-supported trees. In addition, cox1 was identified as a potential single-gene molecular marker for the phylogenetic analysis of relationships among Agaricomycetes species. This study provides the first report of mitogenomes from the Russulaceae family and facilitates the investigation of population genetics and evolution of other ectomycorrhizal fungi.

Transcriptional profiling provides new insights into the role of nitric oxide in enhancing Ganoderma oregonense resistance to heat stress.

Ganoderma is well known for its use in traditional Chinese medicine and is widely cultivated in China, Korea, and Japan. Increased temperatures associated with global warming are negatively influencing the growth and development of Ganoderma. Nitric oxide is reported to play an important role in alleviating fungal heat stress (HS). However, the transcriptional profiling of Ganoderma oregonense in response to HS, as well as the transcriptional response regulated by NO to cope with HS has not been reported. We used RNA-Seq technology to generate large-scale transcriptome data from G. oregonense mycelia subjected to HS (32 °C) and exposed to concentrations of exogenous NO. The results showed that heat shock proteins (HSPs), "probable stress-induced proteins", and unigenes involved in "D-amino-acid oxidase activity" and "oxidoreductase activity" were significantly up-regulated in G. oregonense subjected to HS (P < 0.05). The significantly up-regulated HSPs, "monooxygenases", "alcohol dehydrogenase", and "FAD/NAD(P)-binding domain-containing proteins" (P < 0.05) regulated by exogenous NO may play important roles in the enhanced HS tolerance of G. oregonense. These results provide insights into the transcriptional response of G. oregonense to HS and the mechanism by which NO enhances the HS tolerance of fungi at the gene expression level.

Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare. METHODS: The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs) and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real-time PCR. The correlation between the expression of DELs and various clinicopathological characteristics was analyzed using Student's t-test or linear regression. Co-expression networks between DEGs and DELs were constructed through Pearson correlation co-efficient and enrichment analysis. Validation of DELs' functions including proliferation and migration was performed via loss-of-function RNAi assays. RESULTS: In this study, we identified 439 DEGs and 214 DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs, including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition, the co-expression network analysis between DEGs and DELs showed that DELs were involved with metabolic, cell cycle, chemical carcinogenesis, and complement and coagulation cascade-related pathways. The silencing of the endogenous level of NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both SK-HEP-1 and SMMC-7721 HCC cells. CONCLUSION: These findings not only add knowledge to the understanding of genome-wide transcriptional evaluation of HCC but also provide promising targets for the future diagnosis and treatment of HCC.

Identification of Specific Long Non-Coding RNA Expression: Profile and Analysis of Association with Clinicopathologic Characteristics and BRAF Mutation in Papillary Thyroid Cancer.

BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription polymerase chain reaction were used to detect and verify changes to the transcriptome profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathologic characteristics was analyzed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs. Furthermore, the specific subgroup patterns of the PTC transcriptome remodeled by BRAF mutations were also analyzed. RESULTS: A total of 188 lncRNAs and 505 mRNAs were differentially expressed in 50% or more of the PTC tissues (fold change >2; p < 0.05) as assessed by RNA-sequencing compared with paired normal adjacent tissues. Forty-seven lncRNAs and 39 mRNAs were verified in 31 pairs of PTC specimens using quantitative reverse transcription polymerase chain reaction, and the results were consistent with the RNA sequencing data. The lncRNAs NONHSAT076747 and NONHSAT122730 were associated with lymph node metastasis, and NONHSAG051968 expression was negatively correlated with tumor size. A co-expression network between differentially expressed lncRNAs and protein-coding RNAs was constructed and analyzed, and functional analysis suggested that the differentially expressed genes mainly participate in ECM-receptor interactions and the focal adhesion pathway. Furthermore, a specific PTC transcriptome subtype pattern stratified by BRAF mutation was also uncovered. The p53 signaling pathway was the most highly enriched pathway among the BRAF mutation-related genes. CONCLUSIONS: This study reveals specific changes to the lncRNA profile associated with PTC, and provides new insight into its pathogenesis. The PTC-associated lncRNAs NONHSAG051968, NONHSAT076747, and NONHSAT122730 might be potential diagnostic and therapeutic targets for PTC patients, and lncRNAs with subtype-specific expression stratified by BRAF mutation might be significant in individual molecular subtypes.

Hepatoid adenocarcinoma of the stomach: Nine case reports and treatment outcomes.

Hepatoid adenocarcinoma (HAC), an extrahepatic tumor, has notable morphological similarities to hepatocellular carcinoma, which has been reported in gastrointestinal tract organs, including the rectum, gallbladder, lung, ovary and urinary bladder. HAC of the stomach (GHAC) is a rare variant of gastric cancer, characterized by aggressive behavior and extremely poor prognosis. Correct diagnosis depends on clinicopathological and immunohistochemical studies. In the present study, we reported nine cases of GHAC who were treated in the First Affiliated Hospital of Zhejiang University, China, from January 2009 to December 2013. All patients underwent radical gastrectomy; among them, one patient had stage I, one had stage II and seven had stage III. Elevated serum α-fetoprotein was observed in eight cases. Until now, only one patient has succumbed, four patients have liver metastases, one has lung metastasis and four remain disease-free. Relatively longer survival requires accurate diagnosis at an earlier stage and active multimodality treatment, including radical gastrectomy and adjuvant chemotherapy.