Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia.

OBJECTIVE: Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients. METHODS: The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification. RESULTS: The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers. CONCLUSIONS: This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach.

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand-receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (-41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.

Microbial production and applications of ß-glucosidase-A review.

ß-Glucosidase exists in all areas of living organisms, and microbial ß-glucosidase has become the main source of its production because of its unique physicochemical properties and the advantages of high-yield production by fermentation. With the rise of the green circular economy, the production of enzymes through the fermentation of waste as the substrate has become a popular trend. Lignocellulosic biomass is an easily accessible and sustainable feedstock that exists in nature, and the production of biofuels from lignocellulosic biomass requires the involvement of ß-glucosidase. This review proposes ways to improve ß-glucosidase yield and catalytic efficiency. Optimization of growth conditions and purification strategies of enzymes can increase enzyme yield, and enzyme immobilization, genetic engineering, protein engineering, and whole-cell catalysis provide solutions to enhance the catalytic efficiency and activity of ß-glucosidase. Besides, the diversified industrial applications, challenges and prospects of ß-glucosidase are also described.

Rapid construction of Escherichia coli chassis with genome multi-position integration of isopentenol utilization pathway for efficient and stable terpenoid accumulation.

The isopentenol utilization pathway (IUP) is potential in terpenoids synthesis. This study aimed to construct IUP-employed Escherichia coli chassis for stably synthesizing terpenoids. As to effectiveness, promotor engineering strategy was employed to regulate IUP expression level, while ribosome-binding site (RBS) library of the key enzyme was constructed for screening the optimal RBS, followed by optimization of concentration of inducer and substrates, the titer of reporting production, lycopene, from 0.087 to 8.67 mg OD600 -1 . As about stability, the IUP expression cassette was integrated into the genome through transposition tool based on CRISPR-associated transposases. Results showed that the strain with 13 copies produced 1.78-fold lycopene titer that of the controlled strain with IUP-harbored plasmid, and it exhibited stable expression after ten successions while the plasmid loss was observed in the controlled strain in the 3rd succession. This strategy provides valuable information for rapid construction of highly effective and stable chassis employing IUP for terpenoids production.

Humanized CD36 (hCD36) mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36.

CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates lipid uptake, advanced oxidation protein products, and immunological recognition, and has roles in lipid accumulation, apoptosis, as well as in metastatic colonization in cancer. CD36 is involved in tumor immunity, metastatic invasion, and therapy resistance through various molecular mechanisms. Targeting CD36 has emerged as an effective strategy for tumor immunotherapy. In this study, we have successfully generated a novel hCD36 mouse (Unless otherwise stated, hCD36 mouse below refer to homozygous hCD36 mouse) strain where the sequences encoding the extracellular domains of the mouse Cd36 gene were replaced with the corresponding human sequences. The results showed that the hCD36 mice only expressed human CD36, and the proportion of each lymphocyte was not significantly changed compared with wild-type mice. Furthermore, CD36 monoclonal antibody could significantly inhibit tumor growth after treatment. Therefore, the hCD36 mouse represent a validated preclinical mouse model for the evaluation of tumor immunotherapy targeting CD36.

The predictive value of CD4, CD8, and C-reactive protein in the prognosis of schistosomal and non-schistosomal colorectal cancer.

BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China and occasional outbreaks occur in Europe in recent years. The relationship between inflammation caused by Schistosoma japonicum and colorectal cancer (CRC) is still obscure, and the inflammation based prognostic systems of schistosomal colorectal (SCRC) has rarely been reported. AIM: To explore the different roles of tumor infiltrating lymphocytes (TILs) and C-reactive protein (CRP) in SCRC and in Non-schistosomal CRC (NSCRC), providing a possible predictive system to evaluate outcomes and to improve the risk stratification for CRC patients, especially for CRC patients with schistosomiasis. METHODS: Three hundred fifty-one CRC tumors were evaluated for density of CD4 + , CD8 + T cells and CRP in intratumoral and stromal compartments by immunohistochemical using tissue microarray. RESULTS: There were no association between TILs and CRP and schistosomiasis. Multivariate analysis identified stromal CD4 (sCD4) (p = 0.038), intratumoral CD8 (iCD8) (p = 0.003), schistosomiasis (p = 0.045) as independent prognostic factors for overall survival (OS) in the whole cohort; and sCD4 (p = 0.006) and iCD8 (p = 0.020) were independent prognostic factors for OS in the NSCRC and SCRC set, respectively. Besides, we found that there were no differences of TILs and CRP, which were distributed in different areas of tumor tissue, between CRC patients with and without schistosomiasis. CONCLUSION: The results remind us that different subtypes of TILs have distinguished biological behavior and prognosis value in the immune microenvironment of NSCRC and SCRC patients. Meanwhile, the findings require us to stratify patients with schistosomiasis and this might facilitate patient counseling and management.

Feasibility of ultrasound in the diagnosis of neonatal respiratory distress syndrome in preterm infants.

BACKGROUND: The aim of this study was to investigate the feasibility of lung ultrasound in the diagnosis of neonatal respiratory distress syndrome (NRDS) in preterm infants. METHODS: One hundred and nine preterm infants were prospectively recruited. Three ultrasound diagnostic criteria were developed to diagnose preterm infants with NRDS: (A) thickened or not smooth pleural line, part of the lung field shows diffuse 'B-line' sign or alveolar-interstitial syndrome (AIS); (B) thickened or not smooth pleural line, all lung fields show AIS, signifying the 'white lung' sign; (C) thickened or rough pleural line, 'white lung' sign and 'lung consolidation' sign can be observed in any lung field. RESULTS: The sensitivity and negative predictive value of NRDS in preterm infants with diagnostic criteria A were 100%, but the specificity and positive predictive value were 67.95 and 55.36%, respectively. The specificity and positive predictive value of diagnostic criteria B and C were 100%, while the 95% CI of diagnostic criteria B was narrower than diagnostic criteria C. The sensitivity and negative predictive value of diagnostic criteria B were higher than that of diagnostic criteria C. Of the 31 NRDS cases, 15 cases had severe NRDS and the other 16 did not have severe NRDS. CONCLUSION: Thickened or rough pleural line with white lung sign is an important characteristic for the diagnosis of NRDS by lung ultrasound. White lung sign combined with the lung consolidation sign had high diagnostic efficacy when distinguishing severe NRDS from not severe NRDS.

Comparison of the prognostic value of stromal tumor-infiltrating lymphocytes and CD3 + T cells between schistosomal and non-schistosomal colorectal cancer.

AIM: To compare the prognostic value of tumor-infiltrating lymphocytes (TILs) and CD3 + cells and CD20 + cells between schistosomal colorectal cancer (SCRC) and non-schistosomal CRC (NSCRC). BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China, and occasional outbreaks occur in Europe recently. The role of immune cells in the immune microenvironment of SCRC and NSCRC is remaining obscure, and the inflammation-based prognostic systems of SCRC has rarely been reported. METHODS: HE-stained sections of 349 colorectal cancer (CRC) tumors, which were completely resected, were evaluated for density of TILs. Meanwhile, we evaluated CD3 + T lymphocytes and CD20 + B lymphocytes by immunochemistry. The relationship of these infiltrating immune cells with clinicopathological features, including schistosomiasis, and clinical outcomes was evaluated, and the prognostic roles of TILs in SCRC and NSCRC were explored. RESULTS: Except for age (P < 0.0001), there were no significant differences between NSCRC and SCRC patients in clinicopathological features (P > 0.05). Beside, the positive expression pattern of sTILs, iTILs, CD3, and CD20 between NSCRC and SCRC patients was also similar (P > 0.05). In the whole cohort, sTILs and CD3 were defined as independent prognostic factors (P = 0.031 and P = 0.003, respectively). CD3 was an independent prognostic factor both in the NSCRC and SCRC set (P = 0.026 and P = 0.045, respectively). Higher sTILs, CD3, and CD20 were correlated with less aggressive tumor characteristics in the whole cohort and in subgroups. CONCLUSION: Although CD3 was an independent prognostic factor for both NSCRC and SCRC set, there were no significant differences between SCRC and NSCRC patients in sTILs, CD3, CD20, and in other clinicopathological features.

The establishment of B cell-deficient Igh-J KO mouse model by gene editing and efficacy evaluation.

Over the last few years, immunotherapy has made significant progress in treating various cancers with therapeutic antibodies. However, therapeutic antibodies have been validated for inducing an unintended immune response in human and animal models, which leads to the emergence of anti-drug antibodies (ADAs) and affects their effectiveness and safety. In preclinical research, ADAs production by B cells may accelerate antibody metabolism and result in missing potential candidate molecules. Thus, it is urgent to develop preclinical models that remove only B cells without affecting the function of T and NK cells. Rearrangement of immunoglobulin heavy chain J gene fragment (Igh-J) is the first link in B cell development, and immunotherapies are currently leaning toward combination treatments with PD-1/PD-L1 antibodies, here we created humanized PD-1, PD-L1 and Igh-J knockout (hPD-1/hPD-L1, Igh-J KO) mice and validated by using the reported high immunogenicity drug M7824 (a protein designed to simultaneously block PD-L1 and TGF-ß pathways, poorly anti-tumor efficacy in immunocompetent mice). Phenotypic analysis revealed that human PD-1 and PD-L1 were detectable in hPD-1/hPD-L1, Igh-J KO mice, but not mouse IgM and IgD. Igh-J KO depleted B cells while increased the percentage of other immune cell types. Meanwhile, the humanization of PD-1/PD-L1 and Igh-J KO had neither effect on the overall development, differentiation, or distribution of T cell subtypes, nor on the activation of NK and T cells, indicating that mice can be used for T and NK-related immunotherapies. Furthermore, M7824 treatment of these B cell-deficient mice inhibited tumor growth significantly, with higher M7824 analog concentrations and lower ADA-positive rates. These findings demonstrate that Igh-J KO mice are an effective and stable preclinical model for testing drugs based on T and NK cells with high immunogenicity in vivo.

Clinical Evaluation of High-Resolution MRI Combined With DWI in Identifying Vulnerable Carotid Plaque.

BACKGROUND: High-resolution magnetic resonance imaging combined with diffusion weighted imaging is used to identify vulnerable plaques (VP) and their characteristic components, and apparent diffusion coefficient (ADC) correlation analysis with serum inflammatory markers to assess plaque vulnerability. METHODS: In this study, 60 eligible patients were included, including 29 patients in VP group and 31 patients in non-VP group (N group). The average ADC value, serum inflammatory marker levels (high-sensitivity C-reactive protein, myeloperoxidase, and erythrocyte sedimentation rate) of the 2 groups were measured, and the characteristics of different plaque components and ADC levels of vascular wall in VP group were compared, to evaluate the correlation between serum inflammatory markers and the mean value of plaque ADC. RESULTS: The results showed that the ADC mean value of the plaques in the VP group was significantly lower than that in the N group, and the levels of hypersensitive C-reactive protein and myeloperoxidase were correlated with the ADC mean value of the plaques. CONCLUSION: The ADC value of plaque measured by high-resolution magnetic resonance imaging combined with diffusion weighted imaging sequence can quantify the identification of VP and its characteristic components, reflect the inflammation of plaque to a certain extent, and thus prevent and treat stroke and other adverse outcomes more effectively.

Nutritional status of patients with pulmonary tuberculosis and anti-tuberculosis treatment effect / 中国热带医学

@#Abstract: Objective To investigate the nutritional status of patients with pulmonary tuberculosis and its effects on conventional anti-tuberculosis treatment, so as to provide a basis for improving the efficacy of conventional treatment of pulmonary tuberculosis. Methods The relevant data of 168 patients with pulmonary tuberculosis admitted to Suining Central Hospital from April 2020 to April 2022 were retrospectively analyzed. Nutritional status of the patients before treatment was investigated using the Mini Nutritional Assessment (MNA) score, and the influencing factors of nutritional status before treatment were analyzed. Therapeutic effects of anti-tuberculosis drugs in the non-nutritional risk group and the nutritional risk group were comparatively analyzed. Results Among the 168 patients, 64 were assessed as having good nutritional status before treatment, 59 had the risk of malnutrition and 45 were malnourished according to the MNA score. Univariate analysis and linear regression analysis showed that age, underlying diseases, and clinical symptoms were factors affecting the MNA score before treatment (t=3.173, 3.718, 2.018, P all<0.05); whereas gender and education level were not factors affecting MNA score before treatment (t=0.065, 0.059, P all>0.05). According to the MNA score before treatment, the patients were dividedinto a non-nutritional risk group (MNA score > 23.5) and a nutritional risk group (MNA score ≤23.5). The negative conversion rate of sputum bacteria, effective rate of focal absorption in the non-nutritional risk group were 92.19% (59/64)and90.63% (58/64) , respectively, which were significantly higher than corresponding 79.85% (82/104)and76.92% (80/104) in the nutritional risk group. The drug resistance rate, adverse reaction rate, and average treatment cost of the no nutritional risk group and nutritional risk group were 7.81% (5/64) and 21.15% (12/104), 15.63% (10/64) and 31.73% (33/104), (0.62±0.13) million yuan and (0.89±0.26) million yuan, respectively, with significant differences (χ2=5.228, 5.071, 7.685, 5.396, 7.728, P all<0.05). Conclusions Patients with pulmonary tuberculosis exhibit poor nutritional status before treatment. The patients’nutritional status is easily affected by age, underlying diseases, and clinical symptoms, thereby affecting the effect of anti-tuberculosis treatment. Therefore, early nutritional intervention for tuberculosis patients should be recommended in order to prevent malnutrition and enhance the effectiveness of anti-tuberculosis treatment.

Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer.

BACKGROUND: The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. METHODS: Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. RESULTS: In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). CONCLUSIONS: The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.

BACKGROUND: Gastric cancer (GC) is one of the most lethal forms of cancer due to the absence of tools for its early detection. Here, we explored critical biomarkers for early diagnosis. MATERIALS AND METHODS: Key biomarkers in serum from patients with early gastric cancer (EGC) and healthy controls (HCs) were identified via mass spectrometry and the expression of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) was evaluated using several methods. Furthermore, ITIH4 expression in sera and exosomes from patients with EGC, advanced GC (AGC), low grade intraepithelial neoplasia (LGN), chronic superficial gastritis with Helicobacter pylori infection (Hpi), other systemic malignant tumors (OSTs), and healthy controls was also evaluated. RESULTS: ITIH4 was identified as a key biomarker in patients with EGC. Its expression level in serum from the EGC group, which showed the highest specificity (94.44%), was significantly higher than those in sera from other GC groups as well as the control. Western blot analysis, immunohistochemical staining, and exosome analysis also confirmed ITIH4 expression in sera from patients with GC, but not in those from healthy individual. CONCLUSION: ITIH4 is a key biomarker in serum from patients with EGC and has potential as a high value diagnostic marker for EGC.

Nephrotoxicity induced by cisplatin is primarily due to the activation of the 5-hydroxytryptamine degradation system in proximal renal tubules.

As a widely used anticancer drug in the clinic, cisplatin has obvious side effects, especially nephrotoxicity. Previous studies have suggested that the accumulation of intracellular reactive oxygen species (ROS) is a hallmark of cisplatin-induced acute kidney injury. This study aimed to investigate the relationship between ROS accumulation induced by cisplatin and 5-HT degradation. In vivo, by HE and TUNEL staining, we found that cisplatin-induced renal lesions and apoptotic regions, which were located in proximal tubular epithelial cells, were also the regions in which tryptophan hydroxylase 1 (Tph1), aromatic l-amino acid decarboxylase (AADC), 5-HT2A receptor (5-HT2AR) and monoamine oxidase A (MAO-A) were overexpressed, as determined by immunohistochemistry. Notably, the 5-HT2AR antagonist sarpogrelate hydrochloride (SH) and the AADC inhibitor carbidopa (CDP) significantly attenuated cisplatin-induced increases in serum creatinine and blood urea nitrogen levels, renal ROS levels, oxidative stress (SOD activity and MDA), proinflammatory cytokine levels (NF-κB, TNF-α and IL-1ß), proapoptotic factor levels (Bax, Bcl-2, C-caspase 3 and C-caspase 9) and the phosphorylation of p38 and STAT3, as well as renal lesions and apoptosis. The combination of SH and CDP could almost abolish the effects of cisplatin challenge. In vitro, the effects of cisplatin challenge and the inhibitory effects of SH and CDP were also observed in HK-2 cells. Additionally, similar to the combination of SH and CDP, the MAO-A inhibitor clorgyline could also abolish the effects of cisplatin challenge. More importantly, by western blotting, we detected that the upregulation of Tph1, AADC and MAO-A expression induced by cisplatin both in vivo and in vitro could be obviously suppressed by SH to decrease 5-HT synthesis and mitochondrial 5-HT degradation. Altogether, these findings suggested that cisplatin-induced nephrotoxicity is due to the activation of the 5-HT degradation system in proximal tubular epithelial cells, including 5-HT2AR and 5-HT synthesis and degradation. 5-HT2AR plays a role by mediating the expression of MAO-A and the 5-HT synthases Tph1 and AADC.

Application and Research of Nursing Products Based on Single Wall Carbon Nanotubes in Personal Health Care.

Single walled carbon nanotubes have special chemical and physical properties, at the same time, they have the advantage of macro maneuverability in maneuverability, so they have the potential of multi-functional applications. At present, composite materials, super capacitors and corresponding personal care products based on carbon nanotubes are widely used in all aspects of people's lives, and these products have obvious functional advantages. In this paper, based on the application of single-walled carbon nanotubes technology in personal care products, the separation and purification of ginsenoside pods, the raw material of high-end washing and care products, was studied. In order to enhance the conductivity and tensile strength of SWNTs, this paper innovatively introduces the purification method of current acid treatment to enhance the performance of SWNTs. Based on the improved single-walled carbon nanotubes technology, the extraction efficiency of the optimized single-walled carbon nanotubes was analyzed. In the end of this paper, the optimized extraction method of ginsenoside pods from SWNTs is compared with the traditional extraction method. The experimental results show that SWNTs has obvious time efficiency advantage.

Application of Nano-Composite Technology for Multi-Empty Carbon Nanotubes in Dressing Change Care.

Using good biocompatibility and antibacterial properties, this project synthesized nano-silver-multiempty carbon nanotube composite nano-carriers. The purpose is to improve the water dispersibility of drug particles and enhance their drug selectivity. This approach improves efficiency and resilience in dressing changes. Two different drugs, nano-silver antibacterial gel and nano-silver-multi-empty carbon nanotube composite anti-bacterial gel, were used to change the wounds by establishing a rat burn wound model. Explore the different effects of these two drugs on burn wound healing, infection, and tissue inflammation in rats, and provide a reference for clinical wound dressing change. The experimental results show that the nano-silver-multi-empty carbon nanotube composite antibacterial gel has a better anti-infective effect on burn wounds. And can effectively reduce the number of dressing changes.

Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer.

AIM: The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients' clinical outcomes. METHODS: Three hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. RESULTS: Colorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III-IV tumors and in patients with lymph node metastasis, but not in patients with stage I-II tumors and in patients without lymph node metastasis. CONCLUSION: Schistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III-IV tumors or patients with lymph node metastasis.

The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer.

OBJECTIVE: The purpose of this study was to explore the prognostic role of c-MYC amplification in colorectal cancer, particularly in schistosomiasis-associated colorectal cancer. METHODS: Three hundred and fifty four cases of colorectal cancer, which were from Qingpu Branch of Zhongshan Hospital affiliated to Fudan University, were retrospectively analyzed in a tissue microarray (TMA) format, with fluorescence in situ hybridization (FISH) assay and immunohistochemistry (IHC). RESULTS: c-MYC gene amplification was found in 14.1% (50 out of 354) of patients with colorectal cancer and was correlated with old age (P = 0.028), positive lymph node metastasis (P = 0.004) and advanced stage tumors (P = 0.002). The overexpression of c-MYC was closely associated with the amplification status (P = 0.023). Kaplan-Meier survival curves for overall survival (OS) showed a statistically significant difference for patients with c-MYC amplification in full cohort of colorectal cancer, stage III-IV set and patients with lymph node metastasis (P = 0.002, 0.034, 0.012, respectively). Further analysis found c-MYC amplification associated with poorer survival in the subgroup of colorectal cancer with schistosomiasis (CRC-S, P < 0.001), but not in colorectal cancer without schistosomiasis (CRC-NS, P = 0.155). By multivariate analysis, c-MYC amplification was an independent poor-prognostic factor in CRC-S set (P = 0.046). CONCLUSIONS: Our study firstly found c-MYC amplification could predict poor prognosis in schistosomiasis-associated colorectal cancer, but not in colorectal cancer without schistosomiasis.

Activation of hedgehog signaling and its association with cisplatin resistance in ovarian epithelial tumors.

Few studies have evaluated Hedgehog (Hh) signaling pathway activation in different types of ovarian tumors including benign, borderline and malignant ovarian tumors. The present study investigated the expression of Hh signaling pathway components (SHH, SMO, PTCH, and GLI1) in 193 ovarian epithelial tumor specimens (including 147 malignant epithelial ovarian cancers, 30 borderline ovarian tumors, 16 benign ovarian epithelial tumors) and 11 normal ovarian epithelial tissues by immunohistochemistry. The results demonstrated widespread expression of Hh pathway molecules in ovarian tumors. However, there was no significant difference in the expression intensity of SHH among the four groups (P>0.05). Statistically significant differences were identified in the expression intensity of the SMO, PICH and GLI1 among groups (P<0.001). In addition, significant differences were also revealed in the expression levels of SMO (P=0.013) and GLI1 (P=0.0005) between the platinum drug-sensitive and drug-resistant groups. The overexpression of SMO and GLI1 was further confirmed in the cisplatin-resistant ovarian cancer cell line A2780/DDP by immunofluorescence, flow cytometry and western blotting. The results revealed that the Hh pathway components SMO, PICH and GLI1 are activated in ovarian epithelial tumors. Novel potential associations between cisplatin resistance and the overexpression of SMO and Gli1 in malignant epithelial ovarian cancer were also observed, which may provide an innovative approach to the treatment of drug resistant ovarian epithelial cancer.

[Optimization of the extraction technology of total flavonoids from Mulgedium tataricum using response surface analysis].

OBJECTIVE: Response surface analysis methodology (RSM) was used to optimize the extraction technology of total flavonoids from Mulgedium tataricum. METHODS: Ethanol concentration, solvent-solid ratio, extraction temperature and extraction time were selected as influencing factors during extraction. The experiment mathematical model was arranged according to Box-Behnken central composite experiment design. RESULTS: The optimal extraction conditions were as following: ethanol concentration 63.78%, solvent-solid ratio 40: 1, extraction temperature 90 degrees C, and extraction time 1.07 h, the predicted value of extraction rate of total flavonoids was 14.04% under the optimum conditions, and the experimental value was 13.79%. CONCLUSION: The combination of Box-Behnken design and response surface analysis can well optimize the extraction technology of total flavonoids from Mulgedium tataricum.