Treatment of primary cardiac angiosarcoma in a 35 weeks pregnant woman.

BACKGROUND: Cardiac angiosarcoma is a rare but highly malignant cardiac tumor. It is characterized by poor prognosis, and current treatment approaches are not effective. CASE PRESENTATION: A 37-year-old female with 35 weeks pregnancy experienced chest tightness and shortness of breath for 1 month. She was diagnosed with primary cardiac angiosarcoma. Delivery of fetus was performed early to treat the mother. The patient underwent resection of the tumor then she was treated with chemotherapy. However, the tumor recurred 11 months after surgery. CONCLUSION: Angiosarcoma is a highly malignant tumor explaining recurrence of the tumor recurred after surgery. Cardiac angiosarcoma should be treated through a comprehensive treatment plan, comprising surgery, radiotherapy, and chemotherapy approaches.

Cutting and Bonding Parafilm® to Fast Prototyping Flexible Hanging Drop Chips for 3D Spheroid Cultures.

A fast and low-cost fabrication process of flexible hanging drop chips for 3D spheroid cultures was proposed by cutting and bonding Parafilm®, a cohesive thermoplastic. The Parafilm® Hanging Drop Chip (PHDC) was assembled by two-layer of Parafilm® sheet with different sizes of holes. The hole on the upper layer of the Parafilm® is smaller than the hole on the bottom layer. The impact of hole size and sample volume on hanging drop formation and 3D spheroid formations in the hanging drop were investigated. The results showed that 20 µL solution on PHDC with a 3 mm hole could form stabile drop and facilitate spheroid formation. The initial cell number determinates the size of the formed spheroids. Exchanging liquid from the upper hole of the PHDC enables the co-culture of two types of cells in one spheroid and drug efficacy testing in hanging drops. The relative expression of cell adhesion and hypoxia-related genes from spheroids in hanging drop and conventional culture plate suggested the relevance of 3D spheroids and in vivo tumor tissue. The economical hanging drop chip can be fabricated without wet chemistry or expensive fabrication equipment, strengthening its application potential in conventional biological laboratories.

One-Step Dip-Coating-Fabricated Core-Shell Silk Fibroin Rice Paper Fibrous Scaffolds for 3D Tumor Spheroid Formation.

Bioscaffolds are important substrates for supporting three-dimensional (3D) cell cultures. Silk fibroin (SF) is an attractive biomaterial in tissue engineering because of its good biocompatibility and mechanical properties. Electrospinning is one of the most often used approaches to fabricate SF fibrous scaffolds; yet, this technique still faces many challenges, such as low yield, residual organic solvents, limited extensibility of fibers, and a lack of spatial control over pore size. To circumvent these limitations, a core-shell SF on rice paper (SF@RP) fibrous scaffold was fabricated using a mild one-step dip-coating method. The cellulose fiber matrix of RP is the physical basis of the 3D scaffold, whereas the SF coating on the cellulose fiber controls the adhesion/spreading of the cells. The results indicated that by tuning the secondary structure of SF on the surface of a SF@RP scaffold, the cell behavior on SF@RP could be tuned. Tumor spheroids can be formed on SF@RP scaffolds with a dominant random secondary structure, in contrast to cells adhering and spreading on SF@RP scaffolds with a higher ratio of ß-sheet secondary structures. Direct culturing of breast cancer MDA-MB-231 and MCF-7, lung cancer A549, prostate cancer DU145, and liver cancer HepG2 cells could spontaneously lead to corresponding tumor spheroids on SF@RP. In addition, the physiological characteristics of HepG2 tumor spheroids were investigated, and the results showed that compared with HepG2 monolayer cells, CYP3A4, CYP1A1, and albumin gene expression levels in HepG2 cell spheres formed on SF@RP scaffolds were significantly higher. Moreover, these spheroids showed higher drug resistance. In summary, these SF@RP scaffolds prepared by the dip-coating method are biocompatible substrates for cell culture, especially for tumor cell spheroid formation.

GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation.

Hydrogen sulfide (H2S) is an endogenous gaseous molecule and plays important biological and neurochemical roles in many processes such as the neural activity and immunity. The arcuate nucleus (ARC) of hypothalamus is a control center for appetite and energy metabolism. AMPK is a gage kinase in the monitoring of energy status and regulation of energy metabolism, and it can be activated by H2S via CaMKKß/AMPK pathway. But the role of H2S in ARC and appetite has not been reported. Here we studied the orexigenic effect of H2S and the mechanisms by means of GYY4137, a water soluble and slow-releasing donor of H2S, and protein sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived H2S increased food intake of mice, augmented the production of neuropeptide Y (NPY), and elevated the protein sulfur-sulfhydrylation level and the activation of AMPK and CaMKKß in ARC. Blocking sulfur-sulfhydrylation with DTT eliminated GYY4137-induced activation of AMPK and CaMKKß. DTT and preventing AMPK activation in ARC with Compound C and Ara-A could both attenuate the orexigenic effect of GYY4137. These findings suggest that H2S enhances appetite through protein sulfur-sulfhydrylation and the activation of AMPK and NPY function in ARC.

Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling.

Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.

[Study on purification of total organic acid and chlorogenic acid in Herba Artemisiae scopariae with macroporous adsorption resin].

OBJECTIVE: To optimize the technological parameters of the purification process for total organic acid and chlorogenic acid in Herba Artemisiae scopariae with macroporous adsorption resin. METHODS: Static and dynamic adsorption-desorption methods were adopted to choose the optimal type of resin. Then orthogonal design L9 (3(4)) and single factor experiment were used to select the optimum purification process conditions. RESULTS: The optimal purification process for total organic acid and chlorogenic acid with HPD200A macroporous adsorption resin were as follows: the diameter height ratio of the resin was 1:6, the sample concentration was 1 g/mL, the absorption velocity was 1 BV/h (1 BV represented one column volume), the ratio of sample to HPD200A macroporous adsorption resin was 1.5:1 (W/W), 3 BV of water was used as purificant and 2 BV of 90% ethanol was used as eluant. Under these conditions, the purity of total organic acid and chlorogenic acid was 588.74% and 567.89%, respectively. CONCLUSION: The established purification process for total organic acid and chlorogenic acid in Herba Artemisiae scopariae with HPD200A macroporous adsorption resin is simple and stable and can be used in industrial production.

Effects of quinestrol as a contraceptive in mongolian gerbils (Meriones unguiculatus).

The contraceptive effects of quinestrol in Mongolian gerbils were examined. The results showed that body weight significantly increased after quinestrol treatment, except in the group that received the highest dose. The gonadosomatic index of ovaries decreased, whereas that of uteri increased, and uterine edema appeared after quinestrol treatment. Histological examination revealed that the ovaries had a lack of mature follicles and corpora lutea and that the myometrium and endometrium of the uteri became thin after quinestrol treatment. Persistent estrous appeared after quinestrol treatment, and time to persistent estrous shortened with increasing doses of quinestrol. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels decreased, whereas estradiol (E2) and progesterone (P4) levels increased after quinestrol treatment, and the effects were dose-dependent. During gestation, the serum E2 levels in the different treatment groups were not significantly different. During gestation in the control groups, the serum P4 levels from days 0 to 15 were higher than in the quinestrol-treated groups; however, they did not show significant differences from days 18 to 24. Doses of 0.1 to 2.7 µg/g quinestrol over 6 days completely inhibited fertility. Birth time was prolonged with increasing doses of quinestrol. The findings suggest that quinestrol has marked estrogenic effects in Mongolian gerbils and may inhibit follicle maturation and ovulation through lowered gonadotropin levels. Uterine edema and abnormal E2 and P4 levels during gestation are important causes of pregnancy failure in quinestrol-treated Mongolian gerbils. Quinestrol causes prolonged inhibition of fertility in Mongolian gerbils.

Effects of levonorgestrel on reproductive hormone levels and their receptor expression in Mongolian gerbils (Meriones unguiculatus).

The effects of levonorgestrel (LNG) on serum levels of reproductive hormones and their receptor mRNA expression in the ovary and uterus of Mongolian gerbils were examined. The results show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased, whereas serum estradiol (E2) and progesterone (P4) decreased profoundly after LNG treatment. LNG down-regulated the mRNA expression of follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), estrogen receptor (ER) ß and progesterone receptor (PR) in the ovary, and ERα and PR in the uterus of Mongolian gerbils. The down-regulated effects were time-dependent and dose-dependent. LNG had no obvious effects on ERα mRNA expression in the ovary. The findings suggest that LNG impairs reproductive hormone receptor expression at the molecular level in Mongolian gerbils. Also, the two ER subtypes may play different roles in the ovary, and ERß may not be the predominant ER subtype in the uterus of Mongolian gerbils. The ovary and uterus may be the important sites of action of LNG through its direct progesterone-like effects in Mongolian gerbils.

Variations in serum gonadotropin and prolactin levels during consecutive reproductive states in Mongolian gerbils (Meriones unguiculatus).

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were examined during consecutive reproductive states in Mongolian gerbils. The results indicate that FSH, LH, and PRL levels peak at proestrus, estrus, and diestrus, respectively. During early gestation in primiparous gerbils, gonadotropin levels were the lowest on day 6. This was followed by an increase in FSH and LH levels until days 18 and 15, respectively, with levels remaining constant until day 21. However, in multiparous gerbils, gonadotropin levels were the lowest on day 12 of gestation and were relatively stable between days 15 to 21. In both primiparous and multiparous gerbils, gonadotropin levels increased rapidly from day 21 of gestation to day 3 of lactation, and kept stable between 6-24 days of lactation. PRL peaked during early gestation on days 9 and 6 in the primiparous and multiparous gerbils, respectively, followed by a decline. PRL levels subsequently peaked again on day 21 before parturition. During lactation, PRL levels peaked on days 6 and 9 in primiparous and multiparous gerbils, respectively, followed by a decline until lactation ended. These findings suggest that variations in gonadotropin during the estrous cycle, gestation, and lactation in Mongolian gerbils are similar to those observed in rats, whereas prolactin levels differ. Changes in gonadotropin and prolactin levels during different reproductive states were found to be similar in primiparous and multiparous gerbils, and were correlated with the reproductive stages of Mongolian gerbils.

Prediction on liver fibrosis using different APRI thresholds when patient age is a categorical marker in patients with chronic hepatitis B.

BACKGROUND: Patient age as a predictive variable plays an important role in some indices and models. It was hypothesized that patient age might be a categorical marker. METHODS: We collected the data of 623 CHB patients with liver biopsies. Two-hundred fifty-two patients could provide the duration of HBsAg-positive. RESULTS: The positive correlation between duration of HBsAg-positive and patient age was statistically significant (r = 0.487, P < 0.001). When the cutoff value of patient age was 33.5 y, the best accuracy for liver fibrosis could be obtained. If we could use APRI threshold value of 0.11 for patients with age ≤ 35 and 0.18 for those > 35 y, we could correctly identify 110 CHB patients with insignificant fibrosis which were free of liver biopsy. For all CHB patients based on the APRI threshold of 0.11, 75 patients could be safely predicted as insignificant fibrosis. CONCLUSIONS: Many more CHB patients with insignificant fibrosis could be free of liver biopsy when we used different APRI threshold values based on patient age, especially in patients with > 35 y. The study indicated that more attention should be paid to the influence of patient age on fibrosis.

Variations of serum estradiol and progesterone levels during consecutive reproductive states in Mongolian gerbils (Meriones unguiculatus).

Serum estradiol (E2) and progesterone (P4) levels were measured by chemiluminescence immunoassay (CLIA) during consecutive reproductive states in Mongolian gerbils. The results show that E2 and P4 levels throughout the estrous cycle in Mongolian gerbils peaked at proestrus and estrus, respectively. During gestation in primiparous and multiparous gerbils, E2 levels reached a small peak on day 6 and a maximum peak on day 21, followed by a slight decline until parturition. Thereafter, they dropped sharply during the first 3 days of lactation and remained stable until lactation ended. P4 levels reached a peak on day 12 during gestation in primiparous gerbils, while they peaked on day 6 in multiparous gerbils. The levels of P4 then decreased until parturition. During lactation, P4 levels peaked on day 9 in primiparous gerbils, while they peaked on day 6 in multiparous gerbils, and then the levels declined gradually until lactation ended. The findings suggest that the variations of E2 levels during the estrous cycle, gestation and lactation in Mongolian gerbils are similar to those observed in rats and mice. Changes in E2 levels during different reproductive states were the same in the primiparous and multiparous gerbils, but the variations in P4 levels did not display this tendency. Changing patterns of E2 and P4 levels are suitable for the reproductive stages of Mongolian gerbils.

Validation of model for end-stage liver disease score to serum sodium ratio index as a prognostic predictor in patients with cirrhosis.

AIM: To evaluate the prognostic ability of model for end-stage liver disease (MELD) to serum sodium (SNa) ratio (MESO) index and to compare the predictive accuracy of the MESO index with the MELD score and the modified Child-Turcotte-Pugh (CTP) score for short-term survival in cirrhotic patients. METHODS: A total of 256 patients with cirrhosis were retrospectively evaluated. The predictive accuracy of the MESO index, MELD score and modified CTP score were compared by the area under the receiver-operator characteristic curve (AUC). RESULTS: Using 1-month and 3-month mortality as the end-point, overall, MESO and MELD were significantly better than the CTP score in predicting the risk of mortality at 1 month (AUC, 0.866,0.819 vs 0.722, P < 0.01) and 3 months (AUC, 0.875,0.820 vs 0.721, P < 0.01). In the low MELD group, the AUC of MESO index (0.758, 0.759) and CTP score (0.754, 0.732) were higher than that of the MELD score (0.608, 0.611) at 1 month and 3 months, respectively (P < 0.01). However, in the high MELD group, the AUC of MESO index (0.762, 0.779) and MELD (0.737, 0.773) were higher than that of the CTP score (0.710, 0.752) at 1 month and 3 months, respectively, although there were no significant differences (P > 0.05). With appropriate cut-offs for the MESO index, the mortality rate of patients in high MESO was higher (57.1% at 1 month and 69.2% at 3 months) than that of the low MESO (5.5% at 1 month and 7.9% at 3 months) (P < 0.01). CONCLUSIONS: The MESO index, which adds SNa to MELD, is a useful prognostic marker and is found to be superior to the MELD score and modified CTP score for short-term prognostication of patients with cirrhosis.

Traditional Chinese medicine Kang Xian Fu Fang I is effective for prophylaxis and treatment of alcoholic liver disease in rats.

BACKGROUND: Reversal of liver fibrosis is one of the key steps in the prevention and treatment of alcoholic liver disease (ALD), but the mechanism is unknown. This study was to investigate the effects of the Chinese medicine Kang Xian Fu Fang I (KXI) on prophylaxis and treatment of ALD in rats and its possible mechanism of action. METHODS: Eighty male Wistar rats were randomly divided into four groups: normal control; ALD model; treatment of ALD with KXI; and prophylaxis of ALD by KXI. At the end of 4, 8, 12 and 16 weeks, five rats from each group were anesthetized and their livers were removed for pathological studies using hematoxylin-eosin and Masson stain, immunohistochemical studies, and flow cytometry for matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Blood samples were taken for hyaluronic acid (HA) assay. RESULTS: Serum HA level and liver collagen content were lower in the groups given KXI for prophylaxis and treatment than in ALD model group (P<0.05). The levels of MMP-2 and MMP-9 were also decreased in the prophylaxis and treatment groups (P<0.05). Immunohistochemistry showed immunoreactive MMP-2 in endothelial cells of the hepatic artery and portal vein, sinusoidal endothelial cells, and sinusoidal cells. Immunoreactive MMP-9 occurred in the hepatic cells around the veins and sinusoidal cells. CONCLUSIONS: KXI can effectively inhibit or reverse the course of ALD. This may be attributable to its capacity to inhibit the expression of MMP-2 and MMP-9.