[Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion].

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

Exploring the molecular mechanism of azole resistance in Aspergillus fumigatus.

Aspergillus infections are increasingly recognized as a global health problem because of limited antifungal drugs and occurrence of azole resistance worldwide. More cyp51-mediated and non-cyp51-mediated mechanisms of azole resistance have been identified in clinical and laboratory studies in recent years with applications of molecular biotechnology including next-generation sequencing, reverse genetics and so on. In this review, current research on the molecular mechanisms of azole resistance in A. fumigatus were presented and summarized and meanwhile the putative clinical relevance of these findings from bench work were discussed. Important aims are to gain more insight to mechanism of azole resistance and provide some efficient lead for prevention strategy.

ZD6474, a small molecule tyrosine kinase inhibitor, potentiates the anti-tumor and anti-metastasis effects of radiation for human nasopharyngeal carcinoma.

PURPOSE: To investigate the capacity for ZD6474, a small molecule tyrosine kinase inhibitor, to enhance anti-tumor and anti-metastasis effects of radiation on human nasopharyngeal carcinoma (NPC). EXPERIMENTAL DESIGN: NPC cell lines and xenograft models were evaluated following treatment with ZD6474 and radiation alone and in combination compared with untreated control mice. RESULTS: Treatment with ZD6474 enhanced the anti-proliferative effect of radiation on NPC cell lines as detected by cell proliferation and apoptosis assays. ZD6474 also induced a significant increase in the radiosensitivity of NPC cells, with radiation enhancement ratios (RERs) ranging from 1.2 to 1.6. Despite the cytotoxicity exhibited by NPC cells following radiotherapy, the invasion and migration of NPC cells was found to be unaffected. In contrast, treatment with ZD6474 strongly inhibited the invasion and migration of NPC cells. When the administration of radiation and ZD6474 was investigated in vitro, the ability of ZD6474 to inhibit activation of the pro-survival signaling pathways induced by radiation was demonstrated. In vivo, ZD6474 significantly enhanced the anti-metastasis effects of radiation, while treatment with radiation and ZD6474 was found to be well tolerated and resulted in a strong inhibition of tumor growth. CONCLUSIONS: Our results suggest the combination of radiation and ZD6474 represents a promising strategy for the treatment of human NPC.

A comprehensive information resource on traditional, complementary, and alternative medicine: toward an international collaboration.

OBJECTIVES: A prototype for a comprehensive information resource for traditional complementary and alternative medicine (TCAM) has been developed to fill the considerable needs of a broad audience for worldwide access to TCAM information. The proposed resource is to be a comprehensive, vocabulary-controlled, integrated, standardized, multimedia information resource for TCAM. It will facilitate international cooperation, promote synergistic development of individual resources, promote dissemination of TCAM knowledge, and map the interrelationships among the TCAM traditions. METHODS: We organized two workshops for representatives of international databases that contain significant information on various aspects of alternative medicine. For the first workshop, we prepared and demonstrated a prototype named Complementary and Alternative Medicine Digital Library (CAMed) to illustrate the anticipated structure, content, and functionality of the comprehensive resource. We then constructed a second prototype to demonstrate the possibilities of searching across the collaborating databases and presented it to the representatives at the second workshop. OUTCOMES: Representatives of nine international databases attended the two workshops, in Bangalore, India (1998), and in Seoul, Korea (1999). We presented the prototypes at the workshops. Prototype I uses a Web interface, and supports browsing and searching from a variety of access points. Prototype II demonstrates a functional system that provides simultaneous access to selected represented databases by searching thesauri of these databases through our system. The group formalized itself as the International Collaboration for Information on Complementary and Traditional Medicine (IC2TM) with a goal of fully realizing the potential of the project.

[Experimental study on inhibitory effect of Chinese herbal compound on hepatocyte cytochrome P450 II E1 expression in rat model of nonalcoholic fatty liver].

OBJECTIVE: To study the effect of Chinese herbal compound (CHC) on hepatocyte cytochrome P450 II E1 expression in rat model of nonalcoholic fatty liver (NFL). METHODS: CHC was given to the models of NFL formed by high fat diet, and changes on pathology of liver and hepatocyte cytochrome P450 II E1 expression, as well as the contents of malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), vitamin E (VitE) and triglyceride (TG) in liver were observed and compared with those in the control group. RESULTS: The fatty degeneration of liver recovered to normal basically in the CHC group. Immunohistochemical examination showed that CHC could inhibit the hepatocyte cytochrome P450 II E1 expression markedly, and restore the liver contents of MDA, SOD, GSH, VitE and TG to near normal range. CONCLUSION: CHC could inhibit the hepatocyte cytochrome P450 II E1 expression markedly in rats with fatty liver, therefore, has the effect of preventing fatty liver.

[Herbological investigation on traditional Chinese medicine gegen].

In this paper, herbological investigation was carried out into a large of Ben-Cao literature that concerned the origin, clinical use and other relevant aspects of Gegen, from which we can judge that Gegen used in ancient times match to that specified in the present Chinese Pharmacopoeia.

[Analysis on chemical composition of genus Pueraria stems from China].

OBJECTIVE: To provide scientific basis for developing and utilizing Pueraria stems. METHOD: The contents of total flavonoid were determined by means of UV spectrophotometry. The isoflavones in stems and roots of nine species of genus Pueraria were analyzed by TLC. RESULTS: The stems and roots are similar in chemical composition. CONCLUSION: Pueraria stems as a potential resource could be used as a substitute for Pueraria roots.

[Preliminary study on therapeutic effect of oxymatrine in treating patients with chronic hepatitis C].

OBJECTIVE: To evaluate the efficacy of oxymatrine in treating chronic hepatitis C and its mechanism. METHODS: Forty-three patient were divided randomly into the treated group (20 cases) and the control group (23 cases). The treated group was given oxymatrine 600 mg per day intramuscularly, and the control group was given the general liver protective agents such as vitamins. The therapeutic course of both groups was 3 months. RESULTS: HCVRNA of 8 in 17 cases (47.1%) of the treated group converted to negative, while in 18 cases of the control group, the negative conversion only took place in 1 patient (5.6%), the negative conversion rate was significantly higher in the treated group than that in the control group (P < 0.05). The normalization rates of serum alanine transaminase (ALT) of the treated group after 1 month and 2 months treatment was higher than that of the control group, but after 3 months treatment, the normalization rates of the two groups were not different significantly. Plasma level of soluble interleukin-2 receptor and serum level of collagen type IV in the treated group were lowered significantly after treatment, but in the control group, there were no significant change, the difference between the two groups was significant (P < 0.01, P < 0.05). CONCLUSION: Oxymatrine is effective in inhibiting proliferation of HCV, antagonisting liver fibrosis and regulating immune reaction of the host, so it could be a safe, effective drug in treating chronic hepatitis C.

[Diagnostic significance of cuticular patterns on corolla surface from Pueraria spp].

OBJECTIVE: To provide reference materials for the classification and identification of Pueraria spp. by studying the cuticular patterns on corolla surface. METHOD: The cuticular patterns of corolla were observed under SEM (scanning electron microscope). RESULT: The species of the genus Pueraria are defferent from each other in cuticular patterns. CONCLUSION: The diagnostic characters of the cuticular patterns on corolla surface can be used for the classification and identification of Pueraria spp.