Recent trends in preparation and biomedical applications of iron oxide nanoparticles.

The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.

Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines.

Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.

Aquilariperoxide A, a Sesquiterpene Dimer from Agarwood of Aquilaria sinensis with Dual Antitumor and Antimalarial Effects.

Aquilariperoxide A (1), an unprecedented sesquiterpene dimer characterized by a dioxepane ring connecting two sesquiterpene units via a C-C bond, was isolated from agarwood of Aquilaria sinensis-containing resins. The structure was elucidated by spectroscopic and computational methods. A bioassay revealed that 1 significantly inhibits cell proliferation and migration in human cancer cells. The mechanism of 1 against cancer cells was briefly discussed by analysis of RNA sequence data and epithelial-mesenchymal transition. Besides, the antimalarial activity of 1 was also evaluated.

Single-cell RNA sequencing deciphers the mechanism of sepsis-induced liver injury and the therapeutic effects of artesunate.

Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis. Artesunate (ART) is an anti-malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis. Cecal ligation and puncture (CLP)-induced sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell RNA transcriptome sequencing (scRNA-seq). The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during sepsis and released inflammatory cytokines (Tnf, Il1b, Il6), chemokines (Ccl6, Cd14), and transcription factor (Nfkb1), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of sepsis on liver injury, inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection, which would potentially contribute to its clinical translation for sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of artesunate on sepsis.

Clinicopathologic Predictors of Clinical Outcomes in Mammary Adenoid Cystic Carcinoma: A Multi-institutional Study.

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.

Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice.

BACKGROUND: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage. METHODS: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mouse livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the molecular and cellular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson's trichrome and Sirius red staining. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies. RESULTS: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control group profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis. CONCLUSIONS: TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mouse livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

[Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma].

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ï¼» (5.78±2.69) pg/ mlï¼½ and CXCL-13 ï¼»(0.83±0.59) pg/mlï¼½ in protein elevated group were significantly higher than those in the protein normal group ï¼»IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/mlï¼½ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION: The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

The novel HLA-DRB1*12:01:12 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DRB1*12:01:12 differs from HLA-DRB1*12:01:01:01 by one nucleotide in exon 2.

Periosteal chondroma of the rib: A case report.

BACKGROUND: Periosteal chondroma is a very rare benign tumor that develops adjacent to the cortical surface of bone and beneath the periosteal membrane. Periosteal chondroma of the rib is an extremely rare entity. CASE SUMMARY: The patient was a 43-year-old man who had been incidentally found to have a mediastinal mass 1 mo earlier. Plain computed tomography showed a lobulated soft tissue mass on the right side of the T4/5 vertebra that measured about 47 mm × 28 mm in the transverse view and contained diffuse stippled calcification. The mass caused cortical scalloping of the right fourth rib and marginal bone sclerosis. Enhanced computed tomography showed mild enhancement of the mass. Magnetic resonance imaging showed a lobulated mass on the right side of the thoracic vertebra with long TI and T2 signals, mottling, and patchy long T1 and short T2 signals inside. The lesion had a hypointense rim. Enhanced magnetic resonance imaging showed enhancement predominantly at the periphery of the tumor. The tumor was approached through a right posterolateral thoracotomy, and parts of the fourth and fifth ribs were excised with the tumor. Postoperative pathological analysis revealed periosteal chondroma of the rib. CONCLUSION: Periosteal chondroma of the rib has a low incidence and typical imaging manifestations. Understanding its imaging features is helpful to ensure a correct preoperative diagnosis.

Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA.

BACKGROUND: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood. METHODS: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays. RESULTS: We developed a novel clickable, photo-affinity chloroquine analog probe (CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photo-crosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods. CONCLUSIONS: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled (ABPP) and label-free (MS-CETSA) methods.

Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.

BACKGROUND: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol (Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis. METHODS: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide (LPS). We screened for potential protein targets of Cel using activity-based protein profiling (ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays (CETSA) and surface plasmon resonance (SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown. RESULTS: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS (P < 0.05). Cel bound to Cys424 of pyruvate kinase M2 (PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis (Warburg effect). Cel also bound to Cys106 in high mobility group box 1 (HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin (IL)-1ß. Cel bound to the Cys residues in lactate dehydrogenase A (LDHA). CONCLUSION: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.

Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.

Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.

Skeletal meroterpenoids from Ganoderma petchii mushrooms that potentially stimulate umbilical cord mesenchymal stem cells.

(±)-Petchilactones A-C (1-3), three pairs of enantiomeric meroterpenoids respectively with a 6/6/5/5 or a 5/5/5/7/6 ring system were isolated from Ganoderma petchii. Their structures including absolute configurations were assigned by using spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent a new skeletal meroterpenoid. Biological evaluation found that (-)-1 and (-)-3 could induce umbilical cord mesenchymal stem cells into keratinocyte-like cells.

Pulmonary peripheral glandular papilloma and mixed squamous cell and glandular papilloma frequently harbour the BRAF V600E mutation.

AIMS: Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumour (CMPT)/bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterised. We aimed to reveal the relationship between them. METHODS AND RESULTS: We performed a clinicopathological review and next-generation sequencing (NGS) study of two GPs and five MPs. Histologically, GPs/MPs showed similar cellular and architectural features to CMPTs/BAs, such as bilayered epithelium, bronchiole-associated lesions and skipping (discontinuous) growth pattern. One MP showed partial and inconspicuous endobronchiolar growth and more glandular structures, which was very similar to the appearance of CMPT/BA. BRAF V600E mutation was detected in four papillomas (57.1%, one GP and three MPs). CONCLUSIONS: Overlapping morphological features and comparable mutation profiles support that peripheral GPs/MPs and CMPTs/BAs are on the same disease spectrum. We propose expanding the concept of CMPT/BA and including GP and MP in the CMPT/BA family.

Screening of MYH7 gene mutation sites in hypertrophic cardiomyopathy and its significance.

BACKGROUND: There have been few reports of mutations in the beta-myosin heavy chain (MYH7) gene in hypertrophic cardiomyopathy (HCM), which is associated with sudden cardiac death caused by HCM. This study aimed to screen the mutation sites in the sarcomeric gene MYH7 in Chinese patients with HCM. We also planned to analyze the pathogenicity of the mutation site as well as its significance in clinical and forensic medicine. METHODS: From January 2006 to June 2017, autopsy cases were collected from the Department of Pathology, the Affiliated Hospital of Qingdao University. The experiment was to detect MYH7 gene status in formalin-fixed paraffin-embedded tissues from 18 independent autopsy cases who suffered HCM related sudden death (fatal HCM) and 20 cases without cardiomyopathy. Common mutation exon fragments of MYH7 gene were amplified by polymerase chain reaction. The end-of-deoxygenation method and gene cloning method were further performed to analyze the mutation sites. Homologous comparison among mutant sites was conducted using BLAST online database. RESULTS: The 1336th nucleotide of MYH7 gene at exon 14 was converted from T to G in one HCM case, resulting in the conversion of threonine (Thr) at position 446 to proline (Pro). In another case, the 1402th nucleotide at exon 14 was converted from T to C, resulting in the conversion of phenylalanine (Phe) at position 468 to leucine (Leu). Homologous comparison results showed that the two amino acid residues of Thr446 and Phe468 are highly conserved among different species. CONCLUSIONS: Our results showed fatal HCM harbored mutations of Thr446Pro and Phe468Leu in the MYH7 gene. It is significant for clinical and forensic medicine to further explore the functions and detailed mechanisms of these mutations.

Diffuse Tenosynovial Giant Cell Tumor Around the Temporomandibular Joint: An Entity With Special Radiologic and Pathologic Features.

PURPOSE: Diffuse tenosynovial giant cell tumor (TGCT) of the temporomandibular joint (TMJ) is rare. The aim of the present study was to summarize the clinical, radiologic, and pathologic features of this tumor. MATERIALS AND METHODS: Nine cases of TGCT in the TMJ region were examined. All available radiologic and pathologic documents were carefully reviewed. These cases were grouped into 3 types according to the radiologic features: bone-centered type, intraosseous type, and soft tissue type. Cases reported in the literature were reviewed to better summarize the clinical characteristics. RESULTS: TGCTs in the TMJ region showed some special radiologic and pathologic features. Radiologically, the lesion could be centered in the craniofacial bone or centered in the surrounding soft tissue. Four cases were categorized as the bone-centered type, 1 was categorized as the intraosseous type, and 4 were categorized as the soft tissue type. Pathologically, epithelioid mononuclear cells with abundant eosinophilic cytoplasm and eccentric nuclei were observed in all cases. Chondroid metaplasia was noted in 8 cases. Some areas were similar to giant cell reparative granuloma and chondroblastoma. All patients who underwent complete tumor resection showed no evidence of recurrence at follow-up. Of the 93 reported cases, only 5 developed postoperative recurrence and distant metastasis. CONCLUSION: TGCTs of the TMJ region share similar radiologic and pathologic features as other tumors, which indicates the TGCT might be a special entity within a spectrum of diseases.

Esophageal invasive acantholytic anaplastic Paget's disease: report of a unique case.

Paget's disease (PD) is an intraepithelial growth of neoplastic cells showing glandular differentiation. Primary esophageal PD is extremely rare, with only 14 cases reported to date. We report a case of esophageal PD in a 63-year-old man presenting with progressive dysphagia. On gross examination, the esophageal mucosa had a slightly mottled appearance and felt slightly thickened and indurated. Microscopically, the atypical tumor cells were mostly located in middle to basal cell layers of the squamous epithelium. Some tumor cells were difficult to be distinguished from normal squamous epithelium. Some regions of the lesion showed full-thickness cellular atypia with mitotic figures, and some tumor cells invaded through the basement membrane into the lamina propria, mimicking a squamous cell carcinoma. Acantholytic regions were prominent in the epithelium, and some gland-like clefts were formed. One recurrent laryngeal nerve lymph node showed metastatic foci. Immunohistochemically, tumor cells were positive for cytokeratin (CK) 7, CK8/18, carcinoembryonic antigen (CEA) and Her-2, but negative for CK5/6, p63, S-100 protein and HMB45, yielding the diagnosis of PD. This is the first case report of esophageal invasive Paget's disease (invPD) and the first case report of esophageal acantholytic anaplastic Paget's disease (AAPD).

Asn391Thr Mutation of ß-Myosin Heavy Chain in a Hypertrophic Cardiomyopathy Family.

The present study was performed to identify the genetic abnormalities in a family with familial hypertrophic cardiomyopathy.Peripheral blood samples were collected from 22 members of a Chinese family with hypertrophic cardiomyopathy and 307 healthy controls. A total of 26 candidate pathogenic genes were analyzed in the proband using targeted capture sequencing. Identified mutations were analyzed using Sanger sequencing in all family members and healthy controls.A missense mutation (c.1172A>C, p. Asn391Thr) in exon 12 of MYH7 was identified in eight family members, among which six of them were hypertrophic cardiomyopathy carriers. Three carriers presented with cardiac dysfunction. Four members of this pedigree died suddenly, three of whom were diagnosed with hypertrophic cardiomyopathy.From the results of this study, we concluded that the Asn391Thr mutation of MYH7 is a malignant mutation for HCM and that mutation carriers should get effective treatment to prevent sudden death.

Clinicopathologic features and outcomes of primary cardiac tumors: a 16-year-experience with 212 patients at a Chinese medical center.

Primary cardiac tumors are uncommon, and the majority of them are benign which are curable but can cause significant morbidity if not diagnosed and treated in a timely fashion. The objective of this study was to review the clinicopathologic features and surgical outcomes of patients with primary cardiac tumors in a single medical center in China. We have retrospectively reviewed 212 consecutive adult patients who underwent surgical resection of primary cardiac tumors at our center from January of 2001 to June of 2017. All available clinicopathological features, imaging characteristics, and disease outcomes were summarized and presented. The present series enrolled 180 cardiac myxomas (84.9%) and 32 non-myxoma cases that included hemangioma, lipoma, papillary fibroelastoma, schwannoma, pericardial cyst, teratoma, paraganglioma, lymphoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, and liposarcoma. All patients were diagnosed ante-mortem. The most frequent complaint was dyspnea. Benign tumors accounted for 93.9% of cases (199/212) and malignant tumors accounted for 5.7% (12/212), and the remaining one case was intermediate (paraganglioma). The outcome of benign tumors was favorable and only three recurrent cases were documented (1.5%) after surgical resection. All the seven patients with primary cardiac sarcomas (undifferentiated pleomorphic sarcoma, myxofibrosarcoma, angiosarcoma, and liposarcoma) suffered postoperative recurrence or disease related death. Cardiac myxoma represents the most frequent primary cardiac tumors. The clinical presentations, treatment strategies and outcomes of the primary cardiac tumors depend on the tumor location and histopathological type.