A case report of recurrent leiomyosarcoma with chondrosarcoma differentiation in the abdominal wall and a review of the literature.

Leiomyosarcoma with heterologous differentiation is relatively rare. To date, only 19 cases have been reported in the English literature. Heterologous components frequently show histological pleomorphism, while those exhibiting well-differentiated morphology are seldom reported. Here, we report a 34-year-old female diagnosed with leiomyosarcoma and developed abdominal wall recurrence 8 years after primary surgery. The recurrent tumor mainly comprised well-differentiated chondrosarcoma except a single focus of leiomyosarcoma. Due to the rarity and prolonged onset of such a transition, our case provides insight into the understanding of this phenomenon.

Assessing the chronic hepatitis B adaptive immune response by profiling specific T-cell receptor repertoire.

Challenges in assessing hepatitis B virus (HBV)-specific T cell immunity as an immunological biomarker still remain in chronic hepatitis B (CHB), such as the requirement of large quantities of cells. This study aims to conveniently assess HBV-specific T cells immunity in chronic HBV infected patients. We obtained T cell receptor ß chains (TCRßs) from public databases and six acute hepatitis B patients to establish an HBV-specific TCRßs dataset. For some TCRs from one acute patient, their specificities and epitopes were verified. The potential HBV-specific TCRßs from CHB patients were analyzed using GLIPH2 and established dataset. By analyzing two antiviral therapy cohorts including 42 CHB patients, we showed that individuals with better therapy response may depend more on newly emerging potential HBV-specific TCRßs. In a cross-sectional study containing 207 chronic HBV infected patients, the results exhibited that the characteristics of potential HBV-specific clusters were divergent between CHB and hepatocellular carcinoma patients. Our strategy could profile potential HBV-specific TCRß repertoire using a small blood sample, which will complement traditional methods for assessing the HBV-specific T cell immunity.

Case report: cotyledonoid dissecting leiomyoma in a 49-year-old woman.

Background: Cotyledonoid dissecting leiomyoma (CDL) is much less common than typical leiomyoma. Macroscopically, it displays multinodular, exophytic, placenta-like cystic masses and extends into the broad ligament, pelvic cavity, and retroperitoneal space. The seemingly malignant gross appearance of the tumor has perplexed gynecologists and pathologists; microscopically, it has no malignant characteristics, such as atypical cells, a high mitotic index, or tumor necrosis. To date, only a few cases of CDL have been reported. Here, we report a case of CDL, highlighting its gross and histological appearance, and present a review of the literature. Case Description: A 49-year-old woman presented with a history of progressive constipation of 6 months' duration and a palpable left lower abdominal mass of 1 month's duration. Transvaginal ultrasound revealed a bulky uterus containing 2 subserosal fibroids measuring 9.9 cm × 6.9 cm × 6.3 cm and 8.1 cm × 6.6 cm × 6.8 cm, respectively. An abdominal modified radical hysterectomy and bilateral salpingo-oophorectomy was performed. An intraoperative frozen section showed an angioleiomyoma with edema. However, the postoperative paraffin section confirmed a diagnosis of CDL. No abnormalities were observed at the 6-month follow-up visit. Conclusions: Despite its seemingly malignant gross appearance, CDL, based on its microscopic appearance, is a rare benign tumor and has a favorable prognosis.

The Effect and Mechanism of Curcumin Combined with Carboplatin Chemotherapy Promoting on Apoptosis of Lung Cancer HCC827 Cells.

Objective: To investigate the effect and mechanism of curcumin (CUR) killing lung cancer HCC827 cell spheres. Method: HCC827 cell spheres were cultured in serum-free medium, and the protein expression of CD133, SOX2, EpCAM, and ABCG2 was detected by western blot. MTT was used to evaluate the cell viability of HCC827 cell spheres and HCC827 cell after they were treated by 1, 2, 5, 10, and 20 mg/mL carboplatin (CBP) for 48 h. The inhibitory effects of 10 µM, 50 µM, 100 µM, and 200 µM CUR on GST (glutathione S-transferase) activity in HCC827 cell spheres were determined by colorimetry. The flow cytometry (FCM), western blot, qPCR, luciferase assay, and microscopy were used to detect the ROS levels, cell pelletization ability, ß-catenin, SOX2, and ABCG2 mRNA and the promoter activity of ß-catenin upon of HCC827 cell spheres treated with 200 µM CUR for 48 h. The HCC827 cell spheres were infected with ß-catenin adenovirus, and then cells were treated with 200 µM CUR (and/or no 5 mg/mL CBP) for 24 h. The mRNA and protein expression of ß-catenin, SOX2, and ABCG2 was detected by qPCR and western blot, and cell growth inhibition of HCC827 cell spheres was evaluated by MTT. Result: The expression of stem cells marker CD133, SOX2, EpCAM, and drug resistance-related gene ABCG2 mRNA is higher in HCC827 cell spheres, and HCC827 cell spheres resisted the killing effect of difference doses of CBP. The activity of GST of HCC827 cell spheres was inhibited by 10 µM, 50 µM, 100 µM, and 200 µM CUR. It was a dose-dependent manner. After 200 µM CUR had treated HCC827 cell spheres for 48 h, the level of ROS was significantly increased (P < 0.05), and the mRNA and protein expression of ß-catenin, SOX2, and ABCG2 and promoter activity of ß-catenin were notably decreased (P < 0.05), compared to the control group. Furthermore, the formed-sphere ability of HCC827 sphere was inhibited after cells were treated with 200 µM CUR. 200 µM CUR could suppress the proliferation of HCC827 cell spheres and induced cell apoptosis. The proliferation of HCC827 cell spheres was significantly inhibited, and cell apoptosis rate was increased by 200 µM CUR combined with 5 mg/mL CBP than by 200 µM CUR alone. Upregulation of ß-catenin by adenovirus partly reversed the effect of CUR inhibition of the expression of ß-catenin, SOX2, and ABCG2, compared to empty vector adenovirus group. Additionally, overexpression of ß-catenin significantly remitted the inhibitory effect of 200 µM CUR combined with 5 mg/mL CBP on the proliferation of HCC827 cell spheres. Conclusion: CUR inhibited the cell proliferation and stem cell trait and induced apoptosis in HCC827 cell spheres by the inhibition of GST activity and ß-catenin expression. CUR is expected to become a treatment for lung cancer and lung cancer stem cells.

Stacked Dual-Band Quantum Well Infrared Photodetector Based on Double-Layer Gold Disk Enhanced Local Light Field.

We propose a stacked dual-band quantum well infrared photodetector (QWIP) integrated with a double-layer gold disk. Two 10-period quantum wells (QW) operating at different wavelengths are stacked together, and gold nano-disks are integrated on their respective surfaces. Numerical calculations by finite difference time domain (FDTD) showed that the best enhancement can be achieved at 13.2 and 11.0 µm. By integrating two metal disks, two plasmon microcavity structures can be formed with the substrate to excite localized surface plasmons (LSP) so that the vertically incident infrared light can be converted into electric field components perpendicular to the growth direction of the quantum well (EZ). The EZ electric field component can be enhanced up to 20 times compared to the incident light, and it is four times that of the traditional two-dimensional hole array (2DHA) grating. We calculated the enhancement factor and coupling efficiency of the device in the active region of the quantum well. The enhancement factor of the active region of the quantum well on the top layer remains above 25 at the wavelength of 13.2 µm, and the enhancement factor can reach a maximum of 45. Under this condition, the coupling efficiency of the device reaches 2800%. At the wavelength of 11.0 µm, the enhancement factor of the active region of the quantum well at the bottom is maintained above 6, and the maximum can reach about 16, and the coupling efficiency of the device reaches 800%. We also optimized the structural parameters and explored the influence of structural changes on the coupling efficiency. When the radius (r1, r2) of the two metal disks increases, the maximum coupling efficiency will be red-shifted as the wavelength increases. The double-layer gold disk structure we designed greatly enhances the infrared coupling of the two quantum well layers working at different wavelengths in the dual-band quantum well infrared photodetector. The structure we designed can be used in stacked dual-band quantum well infrared photodetectors, and the active regions of quantum wells working at two wavelengths can enhance the photoelectric coupling, and the enhancement effect is significant. Compared with the traditional optical coupling structure, the structure we proposed is simpler in process and has a more significant enhancement effect, which can meet the requirements of working in complex environments such as firefighting, night vision, and medical treatment.

[Estimating the climatic capacity of food security in Henan Province, China under the future climate change scenarios]. / æœªæ¥æ°”å€™å˜åŒ–æƒ æ™¯ä¸‹æ²³å—çœç²®é£Ÿå®‰å ¨æ°”å€™æ‰¿è½½åŠ›è¯„ä¼°.

To explore the effects of future climate change on food production in Henan Province, the climate potential productivity and its change characteristics in Henan Province were calculated by agro-ecological zone (AEZ) model. This study was based on the production potential and climate resource carrying capacity of summer maize and winter wheat, combined with the observation data of 111 meteorological stations in Henan Province from 1961 to 2017 and the meteorological data under two emission scenarios of RCP4.5 and RCP8.5 in 2041-2080. With the grain demand index under different living standards, we analyzed climate carrying capacity and surplus space of Henan Pro-vince. The results showed that the average climatic potential productivity of maize was 18408.87 kg·hm-2 from 1961 to 2017, with high values in the middle and east, and low values in the west. Compared with the reference period (1981-2010), climatic potential productivity of maize under RCP4.5 and RCP8.5 decreased by 13.0% and 8.0% respectively, with the high value center shifting from the east to the southwest of Henan. The average climatic potential productivity of wheat was 10889.79 kg·hm-2, which was high in the middle region and low in the north. Compared with the reference period, climatic potential productivity of wheat under RCP4.5 and RCP8.5 decreased by 18.6% and 21.7%, respectively. Under the current condition of subsistence and well-off food demand, the maximum carrying capacity of climate resources respectively could support 252 million and 183 million people. In 2070s (2071-2080), the average supporting population of the maximum climate resource carrying capacity (Cmax) would decrease. Compared with the reference period, Cmax under the level of well-off and subsistence would decrease by 9.7% and 18.4% respectively in RCP4.5 scenario, and 7.7% and 16.6% respectively in RCP8.5 scenario. Under current climate condition, the relative surplus rate of climate resources in Henan Province ranged from -93.0% to 356.9%. Compared with the reference period, the relative residual rate of climate resources in the future would reduce nearly 40%.

Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome-related inflammation and modulating cholesterol transport.

Atherosclerosis is a chronic disease characterized by lipid deposition and inflammatory response. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome-facilitated inflammatory responses are crucial in the pathogenesis of atherosclerosis, and thus new therapeutic approaches are emerging that target NLRP3 and inflammation. Here, we explored the anti-atherosclerotic effect and mechanisms of a new rutaecarpine derivative, 5-deoxy-rutaecarpine (R3) in vitro and in vivo. R3 treatment attenuated atherosclerosis development and increased plaque stability in Apoe-/- mice fed a high-fat diet, and decreased levels of inflammatory mediators, such as interleukin-1ß, in the serum of Apoe-/- mice and in oxidized low-density lipoprotein (ox-LDL)-stimulated murine macrophages. R3 treatment inhibited NLRP3 inflammasome activation in the livers of Apoe-/- mice and ox-LDL-stimulated murine macrophages by inhibiting NF-κB and MAPK pathways. Additionally, R3 significantly decreased total cholesterol in the serum and livers of Apoe-/- mice and promoted cholesterol efflux in murine macrophages through upregulating protein expression of ATP-binding cassette subfamily A member 1 and scavenger receptor class B type I/human CD36 and lysosomal integral membrane protein-II analogous-1. Our results demonstrated that R3 prevented atherosclerotic progression via attenuating NLRP3 inflammasome-related inflammation and modulating cholesterol transport.

Combined use of bFGF/EGF and all-trans-retinoic acid cooperatively promotes neuronal differentiation and neurite outgrowth in neural stem cells.

Neural stem cells (NSCs) as sources of new neurons in brain injuries or diseases are required to not only elicit neurons for neuronal repair, but also to enhance neurite outgrowth for neuronal network reestablishment. Various trophic or chemotropic factors have been shown to cooperatively improve NSC neurogenesis. However, effects of combined treatment of all-trans-retinoic acid (RA) with GF (Basic fibroblast growth factor and epidermal growth factor, bFGF/EGF) on neurogenesis of NSCs are poorly understood. To address this question, NSCs were isolated from the forebrains of embryonic mice, and treated with GF and RA either alone or in combination for differentiation in vitro. Neurons and astrocytes differentiated from NSCs were stained for MAP2 and GFAP separately by immunofluorescence. The results indicated that GF displayed superior efficacy in promoting neuronal differentiation, and RA showed better efficacy in advancing neurite outgrowth by increasing both neurite length and number. In addition, higher differentiation efficiency of neurons to astrocytes in RA or GF, or both acted at the early stage. However, more importantly, compared with RA alone, GF and RA in combination enhanced neuronal differentiation. Moreover, the combined use of GF and RA increased the length and number of neurites compared with GF, as well as the relative expression level of Smurf1. In addition, astrocytes induced by GF, RA, or both exhibited a radial glia-like morphology with long processes differing from serum effects, which might in part attribute to the total numbers of neurons. These findings for the first time unveil the roles of combined use of GF and RA on the neurogenesis of NSCs, suggesting that the use of this combination could be a comprehensive strategy for the functional repair of the nervous system through promoting neuronal differentiation, and advancing neurite outgrowth.

Identification of autoimmune type 1 diabetes and multiple organ-specific autoantibodies in adult-onset non-insulin-requiring diabetes in China: A population-based multicentre nationwide survey.

AIMS: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). MATERIALS AND METHODS: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT. RESULTS: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). CONCLUSIONS: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.

E3317 promotes cholesterol efflux in macrophage cells via enhancing ABCA1 expression.

Reverse cholesterol transport (RCT) plays an important role in cholesterol and lipid metabolism. Regulating the activities of key transporters and receptors in RCT, such as ATP-binding cassette transporter A1 (ABCA1), helps to prevent atherosclerotic cardiovascular disease. In this study, we used an ABCA1 promoter luciferase reporter assay to screen 20,000 compounds for ABCA1 upregulators. Compound E3317 (N-(6-butylbenzo[d]thiazol-2(3H)-ylidene)-3-(N-(2-cyanoethyl)sulfamoyl)benzamide)) was identified as a positive hit with an EC50 value of 0.2 µM in ABCA1p-LUC HepG2 cells. Thus, we hypothesized that E3317 might have cholesterol- and lipid metabolism-regulating effects through ABCA1 upregulation. E3317 significantly increased ABCA1 mRNA and protein expression in hepatic L02 cells and RAW264.7 macrophages. E3317 promoted cholesterol efflux to apolipoprotein A-I in RAW264.7 macrophages and significantly decreased lipid accumulation in oxidized low-density lipoprotein-induced murine RAW264.7 macrophages. Further studies using ABCA1 siRNA showed that the promotion of cholesterol efflux and decrease of lipid accumulation by E3317 depended on ABCA1 expression. Mechanistic studies indicated that E3317 regulated ABCA1 expression via activating nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), which plays an important role in the regulation of glucose homeostasis and lipid metabolism. The structure of E3317 was docked in the ligand-binding domain of PPARγ (PBD code: 4EMA) to find the key binding amino acids. Site mutation assays confirmed that Y327 and F363 were the key PPARγ binding epitopes of E3317. Our results revealed that E3317 upregulates ABCA1 expression and thereby promotes cholesterol efflux. E3317 may regulate ABCA1 expression through PPARγ. Our findings provide a new compound, E3317, which may have beneficial cardiovascular effects.

[Effect of Acupuncture Combined with Rehabilitation on Immune and Neural Functions in Elderly Patients with Stroke].

OBJECTIVE: To investigate the therapeutic effect of acupuncture combined with rehabilitation and neuro-immune functional activities in elderly patients with stroke. METHODS: A total of 196 elderly stroke patients were randomly divided into control (rehabilitation exercise) and observation(acupuncture＋ rehabilitation exercise)groups (n＝98 in each). Patients of the control group were treated by general healing treatment including good limb placement, timely conversion of body position, joint-motor exercise, sitting balance exercise, sitting-standing-walking, walking up and down stairs, daily life ability exercise, etc. and those of the observation group were treated by using the same methods mentioned in the control group and manual acupuncture stimulation of Sishencong (EX-HN 1), Xuanli (GB 6), the midpoint of EX-HN 1 and GB 6, Baihui (GV 20), Qubin (GB 7), and the midpoint between GV 20 and GB 7 on the affected side (once a day for three 10-day courses). Serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitive C-reactive protein (hs-CRP) contents were assayed using ELISA, and serum CD 3＋， CD 4＋ and CD 8＋ contents assayed using flow cytometry. The disability severity was assessed by using National Institutes of Health Stroke Scale (NIHSS, for dysneuria), modified Rankin Scale，(mRS, stroke severity), and Barthel Index (BI, performance in activities of daily living), separately. The therapeutic effect was determined according to NIHSS score, clinical symptoms and daily activity ability. RESULTS: On day 30 after the treatment, serum IL-2, IL-6, TNF-α and hs-CRP contents were significantly decreased in the observation group in comparison with its own pre-treatment and day 10 after the treatment, and on day 10 and 30 after the treatment, the above were lower than the control group (P<0.05). On day 30 after the treatment, serum CD 3＋， CD 4＋ and CD 4＋/CD 8＋ levels were significantly increased in both control and observation groups in comparison with their own pre-treatment and 10 days' treatment (P<0.05), while CD 8＋ levels obviously decreased in both groups relevant to their own pre-treatment and 10 days' treatment (P<0.05), and the increased CD 3＋， CD 4＋ and CD 4＋/CD 8＋ levels were significant higher in the observation group than in the control group (P<0.05), and the CD 8＋ level was obviously lower in the control group than in the observation group (P<0.05). On day 30 after the treatment, the NIHSS and mRS scores were significantly decreased in both groups (P<0.05), and significantly lower in the observation group than in the control group (P<0.05); the BI scores were evidently increased in both groups relevant to their own pre-treatment (P<0.05), and the BI level was considerably higher in the observation group than in the control group (P<0.05). The total effective rate was 72.4% (71/98) and 93.9% (92/98) respectively in the control and observation groups, being obviously higher in the latter group than in the former (P<0.05). CONCLUSION: Acupuncture combined with rehabilitation therapy is effective in promoting the recovery of neurological function and in regulating T lymphocyte subsets and the expression of inflammatory factors in elderly patients with stroke.

SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression.

BACKGROUND AND AIMS: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent protein deacetylase. Recent studies have demonstrated that enhancing SIRT1 expression or activity may modulate cholesterol and lipid metabolism. However, pharmacological and molecular regulators for SIRT1 are scarce. Here, we aimed to find novel small molecule modulators of SIRT1 to regulate cholesterol and lipid metabolism. METHODS: A high-throughput screening assay was established to identify SIRT1 activators. Surface plasmon resonance and immunoprecipitation were performed to confirm the interaction of E1231 with SIRT1. Cholesterol assay was performed to demonstrate the in vitro effect of E1231. The in vivo effect of E1231 was evaluated in experimental models. RESULTS: E1231, a piperazine 1,4-diamide compound, was identified as a SIRT1 activator with EC50 value of 0.83 µM. E1231 interacted with recombinant human SIRT1 protein and deacetylated liver X receptor-alpha (LXRα). E1231 increased ATP-binding cassette transporter A1 (ABCA1) expression in RAW 264.7 cells dependent on SIRT1 and LXRα. E1231 promoted cholesterol efflux and inhibited lipid accumulation in RAW 264.7 cells via SIRT1 and ABCA1. In the golden hamster hyperlipidemia model, E1231 treatment decreased total cholesterol and triglyceride levels in both serum and the liver, while increased cholesterol content in feces. Moreover, E1231 increased ABCA1 and SIRT1 protein expression in the liver. In ApoE-/- mice, E1231 treatment reduced atherosclerotic plaque development compared with untreated ApoE-/- mice. CONCLUSIONS: We identified a novel SIRT1 activator E1231 and elucidated its beneficial effects on lipid and cholesterol metabolism. Our study suggests that E1231 might be developed as a novel drug for treating atherosclerosis.

A novel SIRT1 activator E6155 improves insulin sensitivity in type 2 diabetic KKAy mice.

Sirtuin 1 (SIRT1) is an NAD+-dependent protein deacetylase that plays a critical role in controlling energy metabolism, stress response and aging. Hence, enhancing SIRT1 activity could be a potential therapeutic strategy to treat metabolic diseases such as diabetes. However, pharmacological activators for SIRT1 are scarce to date. In this study, using the optimized high throughput screening, we identified E6155, a piperazine 1, 4- diamide compound, as a new small molecular activator of SIRT1. We further found that E6155 significantly upregulated glucose uptake in cultured normal liver cells and skeletal muscle cells through increasing SIRT1 deacetylase activity. In type 2 diabetic KKAy mice, E6155 treatment markedly decreased the level of fasting glucose. Moreover, E6155 improved oral glucose tolerance and insulin tolerance. Euglycemic clamp and the homeostasis model assessment of insulin resistance index showed that E6155 ameliorated the insulin resistance and increased insulin sensitivity in diabetic mice. Mechanistically, we observed that the antidiabetic effects of E6155 were involved in SIRT1 dependent activation of LKB1/AMPK and IRS1/AKT pathways. In conclusion, our findings identified E6155 as a novel SIRT1 activator and suggested that E6155 could be a promising drug candidate for treating insulin resistance and diabetes.

Cross-section control of stacked nanowires formed by Bosch process and oxidation.

The cross-sectional shape of the stacked silicon nanowires (SiNWs) formed by the Bosch process and stress-limited oxidation is studied in this paper. Under the condition of high temperature oxidation, the resulting nanowires highly resemble the initial shapes resulting by the Bosch process. The effects of etching and passivation in the Bosch process are modeled to provide a guideline to control the cross-section of the stacked nanowires.