[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.

[Fibrocartilaginous lipoma: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.

Adjuvant chemotherapy for patients with gastric neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas.

BACKGROUND: The aim of this study was to evaluate whether adjuvant chemotherapy is associated with improved survival in patients with resectable gastric neuroendocrine carcinomas (G-NECs) or mixed adenoneuroendocrine carcinomas (G-MANECs). METHODS: The study included patients with G-NECs or G-MANECs who underwent surgery in one of 21 centres in China between 2004 and 2016. Propensity score matching analysis was used to reduce selection bias, and overall survival (OS) in different treatment groups was estimated by the Kaplan-Meier method. RESULTS: In total, 804 patients with resectable G-NECs or G-MANECs were included, of whom 490 (60·9 per cent) received adjuvant chemotherapy. After propensity score matching, OS in the chemotherapy group was similar to that in the no-chemotherapy group. Among patients with G-NECs, survival in the fluorouracil (5-FU)-based chemotherapy group and the non-5-FU-based chemotherapy group was similar to that in the no-chemotherapy group. Similarly, etoposide plus cisplatin or irinotecan plus cisplatin was not associated with better OS in patients with G-NECs. Among patients with G-MANECs, OS in the non-5-FU-based chemotherapy group was worse than that in the no-chemotherapy group. Patients with G-MANECs did not have better OS when platinum-based chemotherapy was used. CONCLUSION: There was no survival benefit in patients who received adjuvant chemotherapy for G-NECs or G-MANECs.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la quimioterapia adyuvante mejoraba la supervivencia en pacientes con carcinomas gástricos resecables neuroendocrinos (gastric neuroendocrine carcinomas, G-NECs) y carcinomas adenoneuroendocrinos mixtos (mixed adenoneuroendocrine carcinomas, G-MANECs). MÉTODOS: Se incluyeron pacientes con G-NECs y G-MANECs tratados quirúrgicamente en 21 centros en China entre 2004 y 2016. Se utilizó un análisis de emparejamiento por puntaje de propensión para reducir el sesgo de selección y el método de Kaplan-Meier para estimar la supervivencia global (overall survival, OS) de los pacientes en los diferentes grupos de tratamiento. RESULTADOS: En total, se incluyeron en el estudio 804 pacientes con G-NECs y G-MANECs resecables y 490 pacientes (60,9%) recibieron quimioterapia adyuvante. Después del emparejamiento por puntaje de propensión, la OS del grupo con quimioterapia fue similar a la del grupo sin quimioterapia. En los pacientes con G-NECs, la supervivencia en los grupos con quimioterapia basada en 5-FU (fluorouracilo) y de quimioterapia sin 5-FU fue similar a la del grupo sin quimioterapia. Asimismo, la combinación de etopósido y cisplatino o de irinotecán y cisplatino no se asoció con una mejor OS en pacientes con G-NECs. En pacientes con G-MANECs, la OS del grupo con quimioterapia sin 5-FU fue peor que la del grupo sin quimioterapia. Los pacientes con G-MANECs no presentaron una mejor OS cuando se administró quimioterapia basada en platinos. CONCLUSIÓN: La administración de quimioterapia adyuvante en pacientes con G-NECs y G-MANECs no mejoró la supervivencia.

There "ain't no mountain high enough"?: The drivers, diversity and sustainability of China's Rhodiola trade.

ETHNOPHARMACOLOGICAL RELEVANCE: Across Asia, Rhodiola species have been used in Bhutanese, Mongolian, Nepalese, Kazakh, Kyrgyz and Uzbek traditional medical systems. China is globally significant in terms of Rhodiola species diversity, with over 60% (55 species) of the world's 90 Rhodiola species, including 16 species found nowhere else in the world. Since the late 1980's there has been a shift from relatively low demand for infusions using chopped dried Rhodiola roots, to high 21st century demand for a wide variety of processed products. China's trade in Rhodiola products is now very diverse, with use in cosmetics and foods in addition to herbal products. Rhodiola crenulata (Hook.f. & Thomson) H.Ohba is the most widely traded species in China. In addition to R. crenulata and Rhodiola rosea L., 19 Rhodiola other species are used. AIMS OF THE STUDY: These were to: (i) better understand why adulteration occurs in Rhodiola products; (ii) become more aware of what drives the growing market demand for Rhodiola products in China; (iii) find out whether increased demand is reflected in wholesale prices for Rhodiola raw materials traditional medicine markets; (iv) to examine Rhodiola supply chains and (v) given that wild populations are the primary supply source, to review the implications of growing demand for conservation and sustainable use. MATERIALS AND METHODS: Firstly, we assessed growth in the diversity of Rhodiola products using three approaches: (i) by assessing patent applications for Rhodiola products in China (1990-2019); (ii) in 2018, through on-line searches of CFDA (China Food and Drug Administration) records for medicines and dietary supplements that had Rhodiola as an ingredient and (iii) by visiting retail stores in 2018 and 2019 to assess the diversity of commercial Rhodiola based products in trade. Secondly, we visited traditional medicine markets in Yunnan, Sichuan, and Qinghai provinces to investigate the trade in Rhodiola (folk taxonomy, trade names, prices, source areas, levels of processing and grading). Thirdly, we analysed the wholesale price data for Rhodiola raw materials in trade over a 16-year period (2002-2018). Fourthly, as most products come from wild collected Rhodiola species, we documented the extent of Rhodiola cultivation in China. RESULTS: International exports of Rhodiola products from China, particularly extracts, is a major driver of commercial trade. One proxy indicator of Rhodiola product diversification in China has been the rapid rise in patent applications from single applications in 1990 and 1991, to a peak of 1017 patent applications in 2015. Wholesale price data from 2002 to 2018 shows a steady increase in wholesale prices. As the growing market for Rhodiola products in China is currently supplied entirely from wild collection, there are justifiable concerns about sustainability. Commercial cultivation needs to expand to meet future demand. CONCLUSIONS: In contrast to Europe and North America, where R. rosea is the focal species in commerce, the trade in Rhodiola products in China is much more diverse. In the face of growing demand, both effective conservation of wild populations and cultivation are needed.

Effect of dietary lactulose supplementation on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers.

A 35 d trial was conducted to evaluate the effects of dietary lactulose on growth performance, nutrient digestibility, meat quality, relative organ weight, and excreta microflora in broilers. A total of 816 1-day-old male Ross broilers (40.2 ± 0.4 g) were allotted to 4 dietary treatments using 12 cages with 17 chicks per cage. Treatments were: 1) CON, basal diet; 2) L05, CON + 0.05% lactulose; 3) L10, CON + 0.10% lactulose; and 4) L15, CON + 0.15% lactulose. Higher (P < 0.05) body weight gain (BWG) and lower (P < 0.05) feed conversion ratio (FCR) were observed in broilers fed the L15 diet compared with those fed the CON diet during d 22 to 35. During d 0 to 35, BWG was higher (P < 0.05) and FCR was lower (P < 0.05) in broilers fed lactulose diets than those fed the CON diet. Additionally, broilers fed L15 diets had the highest BWG (P < 0.05) and lowest FCR (P < 0.05). The apparent total tract digestibility (ATTD) of DM and nitrogen (N) was increased (P < 0.05) in broilers fed the L15 diet compared with those fed the CON diet. Drip loss was decreased (P < 0.05) in L10 and L15 treatments compared with CON treatment on d 1, d 3, and d 5. On d 3, lowest (P < 0.05) drip loss was observed in the L15 treatment. Excreta E. coli counts in the L15 treatment were decreased (P < 0.05) on d 14, but Lactobacillus counts in the L15 treatment were increased (P < 0.05) on d 14 and d 35 compared with the CON diet. A linear effect (P < 0.05) was observed on BWG (d 22 to 35), FCR (d 0 to 35), the ATTD of DM and N, drip loss, E. coli (d 14), and Lactobacillus (d 14 and d 35) counts. In conclusion, dietary supplementation of 0.15% lactulose can improve growth performance and nutrient digestibility; as well as increase the proliferation of Lactobacillus and decrease E. coli counts in excreta.

Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients.

BACKGROUND: Data on the efficacy and safety of sorafenib in combination with transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) are lacking. PATIENTS AND METHODS: In this multicenter retrospective study, 222 consecutive HCC patients receiving combination therapy were enrolled between June 2008 and July 2011. RESULTS: Chronic hepatitis B was the predominant cause of HCC (86%). Eighty percent patients were at Barcelona Clinic Liver Cancer (BCLC) stage C, and 86% patients were in Child-Pugh (CP) A class. The overall median survival was 12 months (95% CI 10.1-13.9). The overall incidence of adverse events (AEs) was 87%. In 177 BCLC-C patients, performance status, the number of HCC nodules, Child-Pugh score and macrovascular invasion were significantly associated with overall survival (OS) and were included in the final risk scores (R), where R = 5 × (vascular invasion: 0 if no, 1 yes) + 6 × (CP: 0 if A, 1 if B) + 7 × (no. of lesions: 0 if 1-2, 1 ≥3) + 8 × ( Eastern Cooperative Oncology Group, ECOG: 0 if 0, 1 ≥1). CONCLUSIONS: Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.

Bioactivity-guided fractionation for anti-inflammatory and analgesic properties and constituents of Xanthium strumarium L.

The aim of this study was to fractionate an extract of Xanthium strumarium L. (EXS) and to investigate the anti-inflammatory and analgesic properties of the extract and its fractions. The ethanol extract of X. strumarium (EXS) was fractionated on the basis of polarity. Among the different fractions, the n-butanol fraction showed the highest anti-inflammatory activity in the croton-oil-induced ear edema test and furthermore reduced the number of writhings induced by acetic acid in mice in a dose-dependent manner. This indicates that the n-butanol fraction of X. strumarium possesses potent analgesic effects which are likely to be mediated by its anti-inflammatory activity. Bioassay-guided fractionation of EXS led to the isolation and identification of ten caffeoylquinic acids and three heterocyclics by HPLC-DAD-MS(n) from the active n-butanol fraction, implying that the active compounds are polar in nature. The isolated caffeoylquinic acids could partially explain the antinociceptive effect of X. strumarium polar extract.

Two new xanthones from Hypericum japonicum.

Two new xanthones, 1,6-dihydroxyisojacereubin-5-O-beta-D-glucoside (1) and 3,6,7-tri-hydroxy-1-methoxy-xanthone (2), were isolated from Hypericum japonicum. The structural elucidation of the isolated compounds were primarily based on HREIMS, EIMS, UV, IR, 1D-, and 2D-NMR analyses, including COSY, HMQC, HMBC, and NOESY correlations.

Inhibition of nicotine-DNA adduct formation in mice by six dietary constituents.

Nicotine [3-(1-methyl-2-pyrrolidinyl)-pyridine] is a major alkaloid in tobacco products and has proven to be a potential genotoxic compound. Many natural dietary products can suppress the DNA adduction, and hence act as inhibitors of cancer. In this study, we investigated the inhibitory effects of curcumin, garlic squeeze, grapeseed extract, tea polyphenols, vitamin C, and vitamin E on nicotine-DNA adduction in vivo using an ultrasensitive method of accelerator mass spectrometry (AMS). The results demonstrated that all the dietary constituents induced marked dose-dependent decrease in nicotine-DNA adducts as compared with the control. The reduction rate reached about 50% for all agents, except garlic squeeze (40%), even at its highest dose level. Amongst the six agents, grapeseed extract exhibited the strongest inhibition to the DNA adduct formation. Therefore, we may arrive at a point that these dietary constituents are beneficial to prevent the harmful adduct formation, and thus to block the potential carcinogenesis induced by nicotine.

Ontogenesis of proopiomelanocortin and its processing to beta-endorphin by the fetal and neonatal rat brain.

A number of reports suggest that beta-endorphin (beta-END) may play an important role in the regulation of cell proliferation and neuronal differentiation. Proopiomelanocortin (POMC), the common precursor ofadrenocorticotropic hormone and beta-END, is detected very early in embryonic life in hypothalamic neurons of the developing rat. However, very little is known about the degree to which POMC is processed to beta-END during fetal and early postnatal life. Thus, it was the objective of the present study to estimate the hypothalamic content of POMC mRNA, as well as the biosynthesis and posttranslational processing of POMC by hypothalamic neurons on fetal day 20 and on days 1, 8 and 22 of postnatal life. Hypothalamic POMC mRNA, as determined by Northern blot analysis, was higher on fetal day 20 than on postnatal days 1, 8 and 22. A higher rate of incorporation of [(3)H]phenylalanine into beta-END immunoreactive peptides was observed on fetal day 20 than on postnatal day 1. However, the rate of incorporation was significantly increased by day 8 of postnatal life and was similar to that on day 22. POMC was processed to beta-lipotropin (beta-LPH) and beta-END at all ages examined, but the relative proportions of POMC:beta-LPH:beta-END changed during development. Thus, beta-END accounted only for 34.89 +/- 6.14% of the total [(3)H]phenylalanine-labeled beta-END immunoreactive peptides on fetal day 20, while it accounted for 57. 37 +/- 5.20, 62.81 +/- 1.38 and 79.25 +/- 6.57% on days 1, 8 and 22 of postnatal life, respectively. Thus, POMC is processed to a considerable extent into beta-END-sized peptides by the fetal hypothalamus and may influence brain development. Furthermore, the rate of processing of hypothalamic POMC into beta-END increases with development, probably due to the increased activity of the enzymes specific for POMC processing.

[Effect of jiaweiyiguanjian decoction on hypothalamus-pituitary-thyroid gland (HPT) in rat model with Yin-deficiency of liver and kidney induced by slow irritation].

OBJECTIVE: To explore the mechanism of Jiaweiyiguanjian decoction in nourishing the liver and kidney. METHOD: A rat model with Yin-deficiency of liver and kidney was made by way of slow irritation. Thyrotropin-releasing-hormone(TRH) of thyron and blood, TSH of pituitary and blood, thyroxine, 3,5,3',5-tetraiodothyronine(FT4) and 3,3',5-traiodothyronine(FT4), 3,3',5-traiodothyronine(rT3) were used as indexes to study the effect of the decoction on HPT. RESULT: The TRH Secretion from hypothalamus increased (P < 0.05), TSH of pituitary and blood reduced(P < 0.05), FT3 and FT4 of blood decreased at the same time and rT3 of blood, increased. The indexes of the treatment group were found almost the same as the those of the normal control group. CONCLUSION: Jiaweiyiguanjian Decoction could adjust HPT.

[Effect of L-dicentrine on contraction of rat stomach muscle strips].

OBJECTIVE: To study the effect of L-dicentrine on the contraction of rat stomach muscle strips induced by 5-HT, histamine K+ and Ca2+. METHOD: In-vitro experimenting on rat stomach muscle strips. RESULTS: The contraction of the strips induced by 5-HT histamine K+ and Ca2+ after high K+ depolarization was markedly inhibited by L-dicentrine or papaverine, showing a non-competitive antagonism. The contraction induced by 5-HT was inhibited by L-dicentrine in Ca2+ free solution. L-Dicentrine inhibited the contraction induced by 5-HT, depending on Ca2+ released from the intracellular store. When the Ca2+ concentration in both solutions was restored, L-dicentrine did not influence the contraction significantly. CONCLUSION: L-Dicentrine could relax the rat stomach smooth muscle. In rat stomach smooth muscles there exist 5-HT receptors.

Effect of vacuolar proton ATPase on pHi, Ca2+, and apoptosis in neonatal cardiomyocytes during metabolic inhibition/recovery.

Recently, we found that vacuolar proton ATPase (VPATPase) operates in cardiomyocytes as a complementary proton-extruding mechanism. Its activity was increased by preconditioning with resultant attenuation of intracellular acidification during ischemia. In this study, we examined whether VPATPase-mediated proton efflux during metabolic inhibition/recovery may spare Na+ overload via Na+-H+ exchange, attenuate Na+-Ca2+ exchange, and decrease apoptosis. Neonatal rat cardiomyocytes were subjected to 2- to 3-hour metabolic inhibition with cyanide and 2-deoxyglucose and 24-hour recovery. The effect of VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i was studied by flow cytometry with propidium iodide, seminaphthorhodafluor (SNARF)-1-AM, and indo-1-AM staining, respectively. VPATPase inhibition increased the amount of apoptosis measured after 24 hours of recovery and abrogated the protective effect of inhibition of Na+-H+ exchange by (5-N-ethyl-N-isopropyl)amiloride (EIPA). Dual blockade of VPATPase and Na+-H+ exchange was additive in effect with EIPA on pHi during metabolic inhibition/recovery and recovery from the acid challenge with sodium propionate. VPATPase blockade increased the rate of accumulation of intracellular Ca2+ at the beginning of metabolic inhibition and abrogated the delaying effect of EIPA on intracellular Ca2+ accumulation. These results indicate that VPATPase plays an important accessory role in cardiomyocyte protection by reducing acidosis and Na+-H+ exchange-induced Ca2+ overload.

[Effect of integrated Chinese medicine on early stage of acute cerebral hemorrhage].

The effect of integrated Chinese medicine (ICM) on the convalescent of acute cerebral hemorrhage patients were observed. The results showd that the effect of patients treated with ICM was better than that treated with Western medicine alone on the aspects of absorption of brain hemetoma, elimination of encephaledema and recovery of neural function (P < 0.05, 0.01). It suggested that early application of integrated Chinese medicine is very helpful in rehabilitation of cerebral hemorrhage patients.

[Relationship between the content of central substance P and the analgesic effect of electroacupuncture in rats].

Substance P(SP) immunoreactivity in the rat brain and spinal cord were measured by radioimmunoassay and studied to correlate with the analgesic effect induced by electroacupuncture (EA). The results showed following: (1) There was a significant elevation in SP levels sn the hippocampus, hypothalamus and striatum after 30 min of EA. There was a markedly fall in the spinal cord. Statistical analysis revealed a positive correlation between the EA effect and the SP content in hypothalamus, striatum and statistical analysis revealed a correlation. In the spinal cord. (p less than 0.01), while the SP content in the hippocampus exhibited a similar degree of elevation in non responsive and good responsive animals to EA stimulation. (2) SP levels in the hippocampus, hypothalamus and striatum were increased by electroacupuncture stimulation (3v). The frequency of 1.5Hz was no obvious difference as compared with 100Hz in the effects on brain SP content. (3) SP content in the spinal cord decreased only using electroacupuncture stimulations of combination of higher intensity (3v) and higher frequency (100 Hz). (4) This effect could be blocked by the naloxone (i.p) and LSD (icv), but icv injection of Met-enkephalin antibodies had no affects on them.