Cold-heat combination is a common method in the treatment of ulcerative colitis, which is represented by classic drug pair, Coptidis Rhizoma and Zingiberis Rhizoma.The present study explored the synergetic effects of berberine and 6-shogaol, the primary components of Coptidis Rhizoma and Zingiberis Rhizoma, respectively, on intestinal inflammation and intestinal flora in mice with ulcerative colitis to reveal the effect and mechanism of cold-heat combination in the treatment of ulcerative colitis.The ulcerative colitis model was induced by dextran sulfate sodium(DSS) in mice.The model mice were administered with berberine(100 mg·kg~(-1)), 6-shogaol(100 mg·kg~(-1)), and berberine(50 mg·kg~(-1)) combined 6-shogaol(50 mg·kg~(-1)) by gavage, once per day.After 20 days of drug administration, mouse serum, colon tissues, and feces were sampled.Hematoxylin-eosin(HE) staining was used to observe histopathological changes in colon tissues.Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to observe the changes in the mucus layer of colon tissues.Enzyme-linked immunosorbent assay(ELISA) was employed to detect the serum content of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6).Immunohistochemical method was adopted to detect the protein expression of macrophage surface markers F4/80, mucin-2, claudin-1, and zonula occludens-1(ZO-1) in colon tissues.High-throughput Meta-amplicon library sequencing was used to detect changes in the intestinal flora of mice.The results indicated that the 6-shogaol group, the berberine group, and the combination group showed significantly relieved intestinal injury, reduced number of F4/80-labeled positive macrophages in colon tissues, increased protein expression of mucin-2, claudin-1, and ZO-1, and decreased serum le-vels of TNF-α, IL-1β, and IL-6.Shannon, Simpson, Chao, and Ace indexes of the intestinal flora of mice in the 6-shogaol group and the combination group significantly increased, and Chao and Ace indexes in the berberine group significantly increased.As revealed by the bioinformatics analysis of intestinal flora sequencing, the relative abundance of Verrucomicrobia at the phylum, class, and order levels decreased significantly in all treatment groups after drug administration, while that of Bacillibacteria gradually increased.In the 6-shogaol group and the combination group, Akkermansia muciniphila completely disappeared, but acid-producing bacillus still existed in large quantities.As concluded, both 6-shogaol and berberine can inhibit intestinal inflammation, reduce the infiltration and activation of macrophages, relieve intestinal damage, reduce intestinal permeability, improve the structure of flora, and promote intestinal microecological balance.The combined application of berberine and 6-shogaol has a significant synergistic effect.
Animals ; Berberine/therapeutic use* ; Catechols ; Claudin-1/therapeutic use* ; Colitis/metabolism* ; Colitis, Ulcerative/metabolism* ; Colon ; Dextran Sulfate/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology* ; Inflammation/metabolism* ; Interleukin-6/metabolism* ; Mice ; Mice, Inbred C57BL ; Mucin-2/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.
Breast ; Epithelioid Cells ; Keratins ; Melanins ; Melanoma ; Monophenol Monooxygenase ; Mucin-1 ; Pigmentation ; Skin

Myoepithelioma was recognized as a histological distinct entity by the World Health Organization (WHO) in 1991. Myoepithelial cells are believed to be of ectodermal origin. In salivary glands, the myoepithelial cells that surround the intercalated ducts are spindled, which is in contrast to the large stellate ones that envelop the acini. Myoepithelioma is a benign salivary gland tumor that consists entirely of myoepithelial cells. A 53-year-old man presented with a 1-year history of a painless mass originating from the right parotid gland. The mass grew rapidly reaching a size of approximately 6 cm. The patient had no facial paralysis. The authors performed right parotidectomy. Immunohistochemistry study of this tumor showed that it was positive for vimentin, positive for S-100, focally positive for pancytokeratin, and focally positive for p63 and that it had a Ki-67 labeling index (below 10%). Additionally, the tumor was negative for epithelial membrane antigen, negative for actin, negative for desmin, negative for CD34 and negative for anaplastic lymphoma kinase. The authors present a case of benign spindle cell myoepithelioma of the parotid gland in a 53-year-old man diagnosed after immunohistochemistry study, describing its importance, along with a brief review of the literature.
Actins ; Desmin ; Ectoderm ; Facial Paralysis ; Humans ; Immunohistochemistry ; Lymphoma ; Middle Aged ; Mucin-1 ; Myoepithelioma ; Parotid Gland ; Parotid Neoplasms ; Phosphotransferases ; Salivary Glands ; Vimentin ; World Health Organization

Clear cell odontogenic carcinoma (CCOC), a very rare neoplasm located mostly in the mandible, has been regarded as a benign tumor. However, due to the accumulation of case reports, CCOC has been reclassified as a malignant entity by the World Health Organization. Patients with CCOC present with regional swelling and periodontal indications with variable pain, often remaining misdiagnosed for a long period. CCOC has slow growth but aggressive behavior, requiring radical resection. Histologic analysis revealed the monophasic, biphasic, and ameloblastic types of CCOC with clear cells and a mixed combination of polygonal and palisading cells. At the molecular level, CCOC shows the expression of cytokeratin and epithelial membrane antigen, along with markers that assign CCOC to the sarcoma family. At the genetic level, Ewing sarcoma breakpoint region 1-activating transcription factor 1 fusion is regarded as the key feature for identification. Nevertheless, the scarcity of cases and dependence on histological data delay the development of an efficient therapy. Regarding the high recurrence rate and the potential of distant metastasis, further characterization of CCOC is necessary for an early and accurate diagnosis.
Ameloblasts ; Diagnosis ; Humans ; Keratins ; Mandible ; Mucin-1 ; Neoplasm Metastasis ; Odontogenic Tumors ; Recurrence ; Sarcoma ; Sarcoma, Ewing ; Transcription Factors ; World Health Organization

OBJECTIVETo investigate the effect of ceftriaxone on the intestinal epithelium and microbiota in mice in the early-life stage, as well as the recovery of the intestinal epithelium and reconstruction of intestinal microbiota in adult mice.

METHODSA total of 36 BALB/C neonatal mice were randomly divided into control group and experimental group, with 18 mice in each group. The mice in the experimental group were given ceftriaxone 100 mg/kg every day by gavage within 21 days after birth. Those in the control group were given an equal volume of normal saline by gavage. Immunohistochemistry was used to measure the expression of Ki67, Muc2, and ZO-1 in the intestinal epithelium. qPCR and next-generation sequencing were used to analyze the overall concentration and composition of fecal bacteria.

RESULTSAfter 21 days of ceftriaxone intervention, the experimental group had a significant reduction in body weight, a significant reduction in the expression of Ki67 and ZO-1 and a significant increase in the expression of Muc2 in intestinal epithelial cells, a significant reduction in the overall concentration of fecal bacteria, and a significant increase in the diversity of fecal bacteria compared with the control group (P<0.05). Firmicutes was the most common type of fecal bacteria in the experimental group, and there were large amounts of Staphylococcus and Enterococcus. The experimental group had a certain degree of recovery of the intestinal epithelium, but there were still significant differences in body weight and the structure of intestinal microbiota between the two groups at 56 days after birth (P<0.05).

CONCLUSIONSEarly ceftriaxone intervention significantly affects the development of the intestinal epithelium and the construction of intestinal microbiota in the early-life stage. The injury of the intestinal microbiota in the early-life stage may continue to the adult stage and affect growth and development and physiological metabolism.

Animals ; Animals, Newborn ; Anti-Bacterial Agents ; pharmacology ; Ceftriaxone ; pharmacology ; Female ; Gastrointestinal Microbiome ; drug effects ; Intestinal Mucosa ; drug effects ; Ki-67 Antigen ; analysis ; Mice ; Mice, Inbred BALB C ; Mucin-2 ; analysis ; Zonula Occludens-1 Protein ; analysis

We describe a case of a 61-year-old Korean man who was diagnosed with renal cell carcinoma that was discovered on abdominopelvic computed tomography obtained after the patient complained of back pain. A radical nephrectomy was performed, and the surgical specimen showed a relatively well-circumscribed and yellowish lobulated hard mass. Microscopically, the tumor showed sheets and nests of hypercellular pleomorphic cells with thick fibrous septation, frequent mitoses, and areas of adrenal cortical-like tissue. Immunohistochemical staining revealed that the tumor cells were positive for inhibin-α, vimentin, synaptophysin, and melan A. It also revealed that the tumor cells were negative for pan-cytokeratin, epithelial membrane antigen, paired box 8, α-methylacyl-coenzyme A racemase, CD10, cytokeratin 7, carbonic anhydrase 9, c-Kit, renal cell carcinoma, transcription factor E3, human melanoma black 45, desmin, smooth muscle actin, S-100, chromogranin A, CD34, anaplastic lymphoma kinase, and integrase interactor 1. Based on these histopathological and immunohistochemical findings, we diagnosed the tumor as intrarenal adrenocortical carcinoma arising in an adrenal rest. Several cases of intrarenal adrenocortical carcinoma have been reported, although they are very rare. Due to its poor prognosis and common recurrence or metastasis, clinicians and pathologists must be aware of this entity.
Actins ; Adrenal Rest Tumor ; Adrenocortical Carcinoma ; Back Pain ; Carbonic Anhydrases ; Carcinoma, Renal Cell ; Chromogranin A ; Desmin ; Humans ; Integrases ; Keratin-7 ; Lymphoma ; MART-1 Antigen ; Melanoma ; Middle Aged ; Mitosis ; Mucin-1 ; Muscle, Smooth ; Neoplasm Metastasis ; Nephrectomy ; Phosphotransferases ; Prognosis ; Recurrence ; Synaptophysin ; Transcription Factors ; Vimentin

In colorectal carcinoma, poorly differentiated clusters (PDCs) are a poor prognostic indicator and show morphological continuity and behavioral similarities to micropapillary patterns (MPPs) as well as tumor buds (TBs). Epithelial-mesenchymal transition (EMT) and inhibition of cancer-stromal interactions may contribute to the development of PDCs. To clarify the biological nature of PDCs, we examined immunohistochemical stainings for β-catenin, Ki-67, E-cadherin, epithelial cell adhesion molecule (EpCAM), MUC1, and epithelial membrane antigen (EMA), which are associated with EMT and cancer-stromal interactions. The expression frequencies and patterns of PDCs, TBs, and differentiated neoplastic glands from the tumor center (TC) were compared. In the study group (117 cases), the nuclear β-catenin staining index was higher in PDCs (37.3%) and TBs (43.3%) than in neoplastic glands from TC (8.9%, P < 0.001). The mean Ki-67 labeling index in TC was 71.5%, whereas it was decreased in PDCs (31.2%) and TBs (10.2%, P < 0.001). E-cadherin and EpCAM displayed a tendency to be found along the cell membrane in TC samples (91.5% and 92.3%, respectively), whereas they showed loss of membranous staining in PDC (44.4% and 36.8%, respectively) and TB samples (60.7% and 68.4%, respectively). An inside-out pattern for MUC1 and EMA was frequently observed in PDC (48.7% and 45.3%, respectively) and TB samples (46.2% and 45.3%, respectively), but not in TC samples. Our data demonstrate that there is a pathogenetic overlap among PDCs, TBs, and MPPs and suggest that they might represent sequential growth patterns that branch from common biological processes such as dedifferentiation and alteration in cancer-stromal interactions.
Adenocarcinoma* ; Biological Processes ; Cadherins ; Cell Membrane ; Colorectal Neoplasms ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Mucin-1

PURPOSE: Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid-like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma. MATERIALS AND METHODS: Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)–encoded RNA. RESULTS: Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67–labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative. CONCLUSION: Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required.
Adenocarcinoma, Papillary* ; Adolescent ; Asian Continental Ancestry Group ; Epithelial Cells ; Female ; Glial Fibrillary Acidic Protein ; Herpesvirus 4, Human ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Keratins ; Mucin-1 ; Nasopharynx ; RNA ; Thyroglobulin ; Thyroid Gland ; Transcription Factors ; Vimentin

Syringoid eccrine carcinoma (SEC) is a rare cutaneous malignant tumor thought to be derived from eccrine sweat apparatus. It is usually present in the head, neck and trunk region, and often occurs in the fourth to seventh decades of life. A 94-year-old male patient visited our department with an 80-year history of a lesion showing a 2×2 cm sized well-demarcated round shaped erythematous to pinkish colored nodule with ulcer on his left thigh. Histological findings revealed a tumor consisted mainly of numerous small cords and nests forming luminal or tubular structures and tumor cells showing variable atypia. Some ductal structures showed tadpole appearance. On immunohistochemical staining, epithelial membrane antigen, S-100, cytokeratin 7 and carcinoembryonic antigen were reactive and Ki-67 showed less than 10% positivity. Based on these findings, the final diagnosis was made as SEC. The patient was treated with local wide excision and didn't show any recurrence during the follow-up period of 12 months. Herein, we report a very rare case of SEC which occurred on the left thigh and discuss 10 cases of SEC presented on the extremities, including our case.
Carcinoembryonic Antigen ; Diagnosis ; Extremities ; Follow-Up Studies ; Head ; Humans ; Keratin-7 ; Larva ; Male ; Mucin-1 ; Neck ; Phenobarbital ; Recurrence ; Sweat ; Sweat Gland Neoplasms ; Thigh* ; Ulcer

Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.
Actins ; Angiomyolipoma* ; Carcinoma, Hepatocellular ; Diagnosis ; Epithelioid Cells ; Humans ; Immunohistochemistry ; Liver* ; MART-1 Antigen ; Middle Aged ; Mucin-1 ; Muscle, Smooth ; Perivascular Epithelioid Cell Neoplasms