Analysis of 14 ß-agonists in pork using an automated wooden tip-based solid-phase microextraction device and ultra-high-performance liquid chromatography-tandem mass spectrometry.

This study introduces a cost-effective, automated ultra-high-performance liquid chromatography-tandem mass spectrometry method for the detection of 14 ß-agonists in pork using a novel solid-phase microextraction probe composed of polyacrylonitrile and molecularly imprinted polymer. Integrated into an automated extraction device, the probe optimizes extraction prior to analysis while reducing expenses and time compared to traditional solid-phase extraction procedures. The method validation followed the Chinese National Standard (GB/T 27404-2008) and examined limits of detection, limits of quantification, matrix effects, linearity, intraday, and interday precision. Average recovery rates ranged from 71.6% to 82.2%, with relative standard deviations less than 15%. Limits of detection and limits of quantification ranged from 0.09 to 0.39 and 0.27 to 0.99 µg/kg, respectively. The new method identified positive samples more accurately than the current National Standard GB/T 31658.22-2022 and demonstrated its potential for routine assessment and regulatory compliance in the detection of ß-agonists in pork.

Network pharmacology to unveil the mechanism of suanzaoren decoction in the treatment of alzheimer's with diabetes.

BACKGROUND: Suanzaoren Decoction (SZRD), a well-known formula from traditional Chinese medicine, has been shown to have reasonable cognitive effects while relaxing and alleviating insomnia. Several studies have demonstrated significant therapeutic effects of SZRD on diabetes and Alzheimer's disease (AD). However, the active ingredients and probable processes of SZRD in treating Alzheimer's with diabetes are unknown. This study aims to preliminarily elucidate the potential mechanisms and potential active ingredients of SZRD in the treatment of Alzheimer's with diabetes. METHODS: The main components and corresponding protein targets of SZRD were searched on the TCMSP database. Differential gene expression analysis for diabetes and Alzheimer's disease was conducted using the Gene Expression Omnibus database, with supplementation from OMIM and genecards databases for differentially expressed genes. The drug-compound-target-disease network was constructed using Cytoscape 3.8.0. Disease and SZRD targets were imported into the STRING database to construct a protein-protein interaction network. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on the intersection of genes. Molecular docking and molecular dynamics simulations were conducted on the Hub gene and active compounds. Gene Set Enrichment Analysis was performed to further analyze key genes. RESULTS: Through the Gene Expression Omnibus database, we obtained 1977 diabetes related genes and 622 AD related genes. Among drugs, diabetes and AD, 97 genes were identified. The drug-compound-target-disease network revealed that quercetin, kaempferol, licochalcone a, isorhamnetin, formononetin, and naringenin may be the core components exerting effects. PPI network analysis identified hub genes such as IL6, TNF, IL1B, CXCL8, IL10, CCL2, ICAM1, STAT3, and IL4. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that SZRD in the treatment of Alzheimer's with diabetes is mainly involved in biological processes such as response to drug, aging, response to xenobiotic, and enzyme binding; as well as signaling pathways such as Pathways in cancer, Chemical carcinogenesis - receptor activation, and Fluid shear stress and atherosclerosis. Molecular docking results showed that licochalcone a, isorhamnetin, kaempferol, quercetin, and formononetin have high affinity with CXCL8, IL1B, and CCL2. Molecular dynamics simulations also confirmed a strong interaction between CXCL8 and licochalcone a, isorhamnetin, and kaempferol. Gene Set Enrichment Analysis revealed that CXCL8, IL1B, and CCL2 have significant potential in diabetes. CONCLUSION: This study provides, for the first time, insights into the active ingredients and potential molecular mechanisms of SZRD in the treatment of Alzheimer's with diabetes, laying a theoretical foundation for future basic research.

Analysis of melanoma tumor antigens and immune subtypes for the development of mRNA vaccine.

Melanoma has a high degree of malignancy and mortality. While there are some hopeful clinical trials for melanoma treatment in progress, they have not yet to yield significant long-term cure rates. Cancer vaccines including mRNA are currently one of the most promising strategy for tumor immunotherapy. The aim of this study was to analyze the potential tumor antigens in melanoma that could be used to develop mRNA vaccines and identify suitable vaccine populations. The gene expression data and complete clinical information of 471 melanoma samples and 1 normal tissue were retrieved from TCGA. Then, 812 samples of normal skin and their corresponding gene expression data were obtained from GTEx. Overexpressed genes, mutated genes and IRDEGs are used to identify potential tumor antigens. The relationship between the expression level of potential antigen and prognosis was analyzed in GEPIA, and then the immune cell infiltration was estimated based on TIMER algorithm. The expression profiles of IRDEGs were used to identify consensus clusters and immune subtypes of melanoma. Finally, mutational status and immune microenvironment characterization in immune subtypes were analyzed. Five tumor antigens (PTPRC, SIGLEC10, CARD11, LILRB1, ADAMDEC1) were identified as potential tumor antigens according to overexpressed genes, mutated genes and immune-related genes. They were all associated with OS, DFS and APCs. We identified two immune subtypes of melanoma, named IS1 and IS2, which exhibit different clinical features and immune landscapes. Based on the different immune landscape, we may conclude that IS1 is immunophenotypically "cold", while IS2 is "hot". The present research implicates that PTPRC, SIGLEC10, CARD11, LILRB1 and ADAMDEC1 may be the antigenic targets for melanoma mRNA vaccines and IS2 patients may be more effective to these vaccines.

Preparation and characterization of lutein loaded folate conjugated polymeric nanoparticles.

AIM: To prepare and characterise lutein-loaded polylactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. METHODS: Nanoparticles were prepared using O/W emulsion solvent evaporation and characterised using DLS, SEM, DSC, FTIR and in-vitro release. Lutein-uptake in SK-N-BE(2) cells was determined using flow-cytometry, confocal-microscopy and HPLC. Control was lutein PLGA nanoparticles. RESULTS: The size of lutein-loaded PLGA and PLGA-PEG-FOLATE nanoparticles were 189.6 ± 18.79 nm and 188.0 ± 4.06 nm, respectively. Lutein entrapment was ∼61%(w/w) and ∼73%(w/w) for PLGA and PLGA-PEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies showed ∼1.6 and ∼2-fold enhanced uptake of lutein from PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein, respectively. Cumulative release of lutein was higher in PLGA nanoparticles (100% (w/w) within 24 h) compared to PLGA-PEG-FOLATE nanoparticles (∼80% (w/w) in 48 h). CONCLUSION: Lutein-loaded PLGA-PEG-FOLATE nanoparticles could be a potential treatment for hypoxic ischaemic encephalopathy.

MEF2 transcription factors in human placenta and involvement in cytotrophoblast invasion and differentiation.

Development of the human placenta and its trophoblast cell types is critical for a successful pregnancy. Defects in trophoblast invasion and differentiation are associated with adverse pregnancy outcomes, including preeclampsia. The members of myocyte enhancer factor-2 (MEF2) family of transcription factors are key regulators of cellular proliferation, differentiation, and invasion in various cell types and tissues and might play a similarly important role in regulating trophoblast proliferation, invasion, and differentiation during human placental development. In the present study, using human cytotrophoblast cell lines (HTR8/SVneo and BeWo) and primary human cytotrophoblasts (CTBs), we show that members of the MEF2 family are differentially expressed in human placental CTBs, with MEF2B and MEF2D being highly expressed in first trimester extravillous CTBs. Overexpression of MEF2D results in cytotrophoblast proliferation and enhances the invasion and migration of extravillous-like HTR8/SVneo cells. This invasive property is blocked by overexpression of a dominant negative MEF2 (dnMEF2). In contrast, MEF2A is the principal MEF2 isoform expressed in term CTBs, MEF2C and MEF2D being expressed more weakly, and MEF2B expression being undetected. Overexpression of MEF2A induces cytotrophoblast differentiation and syncytium formation in BeWo cells. During in vitro differentiation of primary CTBs, MEF2A expression is associated with CTB differentiation into syncytiotrophoblast. Additionally, the course of p38 MAPK and ERK5 activities parallels the increase in MEF2A expression. These findings suggest individual members of MEF2 family distinctively regulate cytotrophoblast proliferation, invasion, and differentiation. Dysregulation of expression of MEF2 family or of their upstream signaling pathways may be associated with placenta-related pregnancy disorders.

Involvement of NAC transcription factor SiNAC1 in a positive feedback loop via ABA biosynthesis and leaf senescence in foxtail millet.

MAIN CONCLUSION: The foxtail millet NAC transcription factor NAC1, an ortholog of Arabidopsis NAP, is induced by ABA and senescence and accelerates leaf senescence by promoting ABA biosynthesis. Leaf senescence, a unique developmental stage involving macromolecule degradation and nutrient remobilization, is finely tuned and tightly controlled by different gene families. NO APICAL MERISTEM, ARABIDOPSIS ATAF1, and CUP-SHAPED COTYLEDON (NAC) transcription factors have been demonstrated to be involved in the modulation of leaf senescence in many land plant species. Foxtail millet (Setaria italica L.), an important food and fodder crop, has been studied for its strong stress tolerance and potential to be a biofuel model plant. However, the functional roles of senescence-associated NACs in foxtail millet are still unknown. In this study, we characterized a nuclear localized NAC transcription factor, SiNAC1, which is induced by senescence and concentrated in senescent leaves in foxtail millet. SiNAC1 also positively responds to abscisic acid (ABA) treatment in foxtail millet. Moreover, SiNAC1 promotes the natural and dark-induced leaf senescence by an ABA-dependent manner in Arabidopsis thaliana. NCED2 and NCED3 are elevated by SiNAC1 overexpression, which subsequently promotes ABA biosynthesis in Arabidopsis. Finally, as a homolog of AtNAP, SiNAC1 can partially rescue the delayed leaf senescence phenotype in atnap mutants. Overall, our results demonstrate that SiNAC1 functions as a positive regulator of leaf senescence and is involved in a positive feedback loop via ABA biosynthesis and leaf senescence.

Carotenoid Lutein Selectively Inhibits Breast Cancer Cell Growth and Potentiates the Effect of Chemotherapeutic Agents through ROS-Mediated Mechanisms.

Increasing evidence suggests that dietary carotenoids may reduce the risk of breast cancer. However, anti-breast cancer effects of carotenoids have been controversial, albeit understudied. Here, we investigated the effects of specific carotenoids on a wide range of breast cancer cell lines, and found that among several carotenoids (including ß-carotene, lutein, and astaxanthin), lutein significantly inhibits breast cancer cell growth by inducing cell-cycle arrest and caspase-independent cell death, but it has little effect on the growth of primary mammary epithelial cells (PmECs). Moreover, lutein-mediated growth inhibition of breast cancer cells is quantitatively similar to that induced by chemotherapeutic taxanes, paclitaxel and docetaxel, and exposure to lutein plus taxanes additively inhibits breast cancer cell growth. Analysis of mechanisms showed that lutein treatment significantly increases the intracellular reactive oxygen species (ROS) production in triple-negative breast cancer (TNBC) cells, but not in normal PmECs. Lutein-induced growth inhibition is also attenuated by the radical oxygen scavenger N-acetyl cysteine, suggesting a role for ROS generation in the growth inhibitory effect of lutein on TNBC cells. Additionally, we found that the p53 signaling pathway is activated and HSP60 levels are increased by lutein treatment, which may contribute partly to the induction of growth inhibition in TNBC cells. Our findings show that lutein promotes growth inhibition of breast cancer cells through increased cell type-specific ROS generation and alternation of several signaling pathways. Dietary lutein supplementation may be a promising alternative and/or adjunct therapeutic candidate against breast cancer.

[Effects of virtual reality training on limb movement in children with spastic diplegia cerebral palsy].

OBJECTIVE: To study the effects of virtual reality (VR) training on the gross motor function of the lower limb and the fine motor function of the upper limb in children with spastic diplegia cerebral palsy. METHODS: Thirty-five children with spastic diplegia cerebral palsy were randomly assigned to VR training group (n=19) and conventional training group (n=16). The conventional training group received conventional physical therapy and occupational therapy for three months. The VR training group received VR training and occupational therapy for three months. Grip and visual-motor integration subtests in Peabody Developmental Motor Scales-2 were used to evaluate the fine movement in patients before and after treatment. The D and E domains of the 88-item version of the Gross Motor Function Measure (GMFM-88), Modified Ashworth Scale (MAS), and Berg Balance Scale (BBS) were used to evaluate the gross movement in patients before and after treatment. RESULTS: Before treatment, there were no significant differences in grip, visual-motor integration, fine motor development quotient, scores of D and E domains of GMFM-88, MAS score, or BBS score between the two groups (P>0.05). After treatment, all the indices were significantly improved in the VR training group compared with the conventional training group (P<0.05). CONCLUSIONS: VR training can effectively improve the gross motor function of the lower limb and the fine motor function of the upper limb in children with spastic diplegia cerebral palsy.

Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy.

Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are important causes of blindness among children and working-age adults, respectively. The development of both diseases involves retinal microvascular degeneration, vessel loss and consequent hypoxic and inflammatory pathologic retinal neovascularization. Mechanistic studies have shown that oxidative stress and subsequent derangement of cell signaling are important factors in disease progression. In eye and vision research, role of the dietary xanthophyll carotenoids, lutein and zeaxanthin, has been more extensively studied in adult onset macular degeneration than these other retinopathies. These carotenoids also may decrease severity of ROP in preterm infants and of DR in working-age adults. A randomized controlled clinical trial of carotenoid supplementation in preterm infants indicated that lutein has functional effects in the neonatal eye and is anti-inflammatory. Three multicenter clinical trials all showed a trend of decreased ROP severity in the lutein supplemented group. Prospective studies on patients with non-proliferative DR indicate serum levels of lutein and zeaxanthin are significantly lower in these patients compared to normal subjects. The present review describes recent advances in lutein and zeaxanthin modulation of oxidative stress and inflammation related to ROP and DR and discusses potential roles of lutein/zeaxanthin in preventing or lessening the risks of disease initiation or progression.

[Laparoscopic high uterosacral ligament suspension combined with cervical amputation in treatment of women severe uterine prolapsed at child-bearing period].

OBJECTIVE: To evaluate clinical and sexual outcomes in women with severe uterine prolapsed at child-bearing period undergoing laparoscopic high uterosacral ligament suspension combined with cervical amputation. METHODS: From November 2007 to March 2010, 34 patients ( ≤ 50 years old) with severe uterine prolapse (prolapse group) who had already given birth and underwent laparoscopic high uterosacral ligament suspension combined with cervical amputation in Peking Union Medical College Hospital were enrolled in this retrospective study. All patients were defined as Pelvic Organ Prolapse Quantification (POP-Q) stage III. Follow-up was performed at 1, 6, and 12 months, and then annually. Anatomic failure was defined as ≥ 1 pelvic compartment classified as POP-Q ≥ stage II.Sexual outcomes were assessed at baseline and 3-year follow-up according to validated Short-Form Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Thirty one age-matched women who underwent health examinations during the same time period were selected as a healthy control group. RESULTS: Mean age of women at prolapse group were (39 ± 5) years and average surgery time were (51 ± 8) minutes. No severe intraoperative complications occurred, including urethral twist, bladder and rectum injury, pelvic hemotoma. All patients were followed up for more than 3 years, the mean following up period was 40 months (36-64 months). Based on stage II of POP-Q as recurrence criteria, the anatomical success and patient satisfaction rates were both 100% (34/34). POP-Q point C and D measurements were significantly higher after surgery then those at preoperative values [C:(-5.4 ± 0.6) cm versus (2.2 ± 0.7) cm, D:(-6.7 ± 0.4) cm versus (-4.0 ± 0.7) cm; P < 0.01 for all]. Three years postoperatively, 33 patients were sexually active. Among the 94% (31/33) patients who answered the PISQ-12 questionnaire, there was significant improvement in post- and preoperative total PISQ-12 scores (38 versus 26, P < 0.01) and in all three subscale PISQ-12 domains (P < 0.01 for all). The postoperative PISQ-12 score was similar to that of the control group (38 ± 6 versus 37 ± 3, P > 0.05). CONCLUSION: Laparoscopic high uterosacral ligament suspension combined with cervical amputation conferred satisfying long-term anatomic and sexual function outcomes in women at child-bearing age.

Bioinformatics analysis highlights CCNB1 as a potential prognostic biomarker and an anti-kidney renal papillary cell carcinoma drug target.

Kidney renal papillary cell carcinoma (KIRP) is a common urinary tumor that causes lymph node invasion. Once metastatic, the prognosis is poor and there is a lack of effective early diagnostic markers for this tumor. The expression of CCNB1 in KIRP tumor tissues was significantly higher than that in normal tissues in The Cancer Genome Atlas database with or without the genotype-tissue expression database, and a consistent result was obtained in 32 paired tissues. In addition, CCNB1 expression increased remarkably with the progression of the T and M stages. Moreover, using the online HPA database, we verified that the immunohistochemical scores of CCNB1 in KIRP were higher than those in the normal kidney tissues. The higher expression group of CCNB1 showed a worse prognosis in KIRP. Moreover, the receiver operating characteristic curve, univariate and multivariate analyses, and construction of the column diagram further illustrated that CCNB1 was an independent prognostic factor for KIRP. Meanwhile, CCNB1 could better predict the 1- and 3-year survival rates of KIRP. Six genes were significantly and positively co-expressed with CCNB1. We also found that the CCNB1 high-expression group was enriched in the ECM_RECEPTOR_INTERACTION and FOCAL_ADHESION pathways. Finally, drug sensitivity analysis combined with molecular docking identified 5 targeting drugs with the strongest binding activity to CCNB1. CCNB1 is a potential and reliable biomarker for KIRP diagnosis and can be used to predict the survival of patients with KIRP. The 5 selected drugs targeting CCNB1 may provide new hopes for patients with KIRP metastasis.

Development of a bioluminescent immunoassay based on Fc-specific conjugated antibody-nanoluciferase immunoreagents for determining aflatoxin B1.

Aflatoxin B1 (AFB1) is a potent carcinogen, and is among the most hazardous mycotoxins in agricultural products. Therefore, the development of sensitive and convenient detection methods for AFB1 is significant for food safety against mycotoxins. Herein, a bioluminescent enzyme immunoassay (BLEIA) was developed for ultrasensitive detection of AFB1, based on the novel Fc-specific antibody-nanoluciferase (Ab-Nluc) conjugates which were fabricated using an IgG-binding protein-assisted photo-conjugation strategy. In indirect competitive immunoassay format, the proposed BLEIA exhibited the detection limit of 0.0232 ng mL-1, which was 37.4-fold lower than that obtained using the classical enzyme-linked immunosorbent assay (ELISA) based on Ab-horseradish peroxidase (Ab-HRP) chemical conjugates (0.868 ng mL-1). Meanwhile, the BLEIA exhibited high accuracy and precision. Thus, the proposed Fc-specific Ab-Nluc conjugates-based BLEIA provides an ultrasensitive and reliable method for detecting toxins and has potential for use in food safety monitoring.

Utilizing noncatalytic ACE2 protein mutant as a competitive inhibitor to treat SARS-CoV-2 infection.

Introduction: Angiotensin converting-enzyme 2 (ACE2) is an enzyme catalyzing the conversion of angiotensin 2 into angiotensin 1-7. ACE2 also serves as the receptor of several coronaviruses, including SARS-CoV-1 and SARS-CoV-2. Therefore, ACE2 could be utilized as a therapeutic target for treating these coronaviruses, ideally lacking enzymatic function. Methods: Based on structural analysis, specific mutations were introduced to generate mutants of ACE2 and ACE2-Fc (fusion protein of ACE2 and Fc region of IgG1). The enzyme activity, binding affinity, and neutralization abilities were measured. Results and discussion: As predicted, five mutants (AMI081, AMI082, AMI083, AMI084, AMI090) have completely depleted ACE2 enzymatic activities. More importantly, enzyme-linked receptor-ligand assay (ELRLA) and surface plasmon resonance (SPR) results showed that 2 mutants (AMI082, AMI090) maintained binding activity to the viral spike proteins of SARS-CoV-1 and SARS-CoV-2. In An in vitro neutralization experiment using a pseudovirus, SARS-CoV-2 S1 spike protein-packed lentivirus particles, was also performed, showing that AMI082 and AMI090 significantly reduced GFP transgene expression. Further, in vitro virulent neutralization assays using SARS-CoV-2 (strain name: USA-WA1/2020) showed that AMI082 and AMI090 had remarkable inhibitory effects, indicated by comparable IC50 to wildtype ACE2 (5.33 µg/mL). In addition to the direct administration of mutant proteins, an alternative strategy for treating COVID-19 is through AAV delivery to achieve long-lasting effects. Therefore, AAV5 encoding AMI082 and AMI090 were packaged and transgene expression was assessed. In summary, these ACE2 mutants represent a novel approach to prevent or treat COVID-19 and other viruses with the same spike protein.

Differential effects of polystyrene microplastics on the adsorption of cadmium and ciprofloxacin by tea leaf litter-derived magnetic biochar: Influencing factors and mechanisms.

Water pollution involves the coexistence of microplastics (MPs) and traditional pollutants, and how can MPs influence the adsorption of other pollutants by biochar during the treatment process remains unclear. This study aimed to investigate the influence of polystyrene microplastics (PS MPs) on the adsorption of cadmium (Cd) and ciprofloxacin (CIP) by magnetic biochar (MTBC) in the single and binary systems. MTBC was prepared using tea leaf litter; the effects of time, pH, and salt ions on the adsorption behaviors were investigated; and X-ray photoelectronic spectroscopy (XPS) and density flooding theory analysis were conducted to elucidate the influence mechanisms. Results indicated that PS MPs reduced the pollutants adsorption by MTBC due to the heterogeneous aggregation between PS MPs and MTBC and the surface charge change of MTBC induced by PS MPs. The effects of PS MPs on heavy metals and antibiotics adsorption were distinctly different. PS MPs reduced Cd adsorption on MTBC, which were significantly influenced by the solution pH and salt ions contents, suggesting the participation of electrostatic interaction and ion exchange in the adsorption, whereas the effects of PS MPs on CIP adsorption were inconspicuous. In the hybrid system, PS MPs reduced pollutants adsorption by MTBC with 66.3% decrease for Cd and 12.8% decrease for CIP, and the more remarkable reduction for Cd was due to the predominated physical adsorption, and CIP adsorption was mainly a stable chemisorption. The influence of PS MPs could be resulted from the interaction between PS MPs and MTBC with changing the functional groups and electrostatic potential of MTBC. This study demonstrated that when using biochar to decontaminate wastewater, it is imperative to consider the antagonistic action of MPs, especially for heavy metal removal. PRACTITIONER POINTS: Magnetic biochar (MTBC) was prepared successfully using tea leaf litter. MTBC could be used for cadmium (Cd) and ciprofloxacin (CIP) removal. Polystyrene microplastics (Ps MPs) reduced Cd/CIP adsorption by MTBC. Ps MPs effects on Cd adsorption were more obvious than that of CIP. Ps MPs changed the functional groups and electrostatic potential of MTBC, thus influencing MTBC adsorption.

ß-carotene regulates expression of ß-carotene 15,15'-monoxygenase in human alveolar epithelial cells.

ß-Carotene 15,15'-monooxygenase (CMO1, BCMO1) converts ß-carotene to retinaldehyde (retinal) and is a key enzyme in vitamin A metabolism. CMO1 activity is robust in the intestine and liver, where cmo1 gene transcription may be subject to negative feedback by accumulation of its metabolic products. Evidence from CMO1 null animals also indicates that non-gastrointestinal CMO1 may be required for tissue-specific conversion of ß-carotene into vitamin A. The aim of this study was to investigate the effects of the enzymatic substrate, ß-carotene, on regulation of CMO1 in a cell model of human alveolar pneumocytes. We demonstrate that CMO1 is expressed in human alveolar epithelial (A549) cells and converts ß-carotene into retinal and biologically active retinoic acids (RA). Exposure to ß-carotene suppresses CMO1 expression at both mRNA and protein levels. ß-Carotene, but not all-trans RA, decreases CMO1 promoter activity in a time- and dosage-dependent manner. This ß-carotene-mediated inhibition of CMO1 expression results from decreased binding of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RXRα) in the CMO1 promoter. ß-Carotene treatment also antagonizes PPARγ activity in HEK293 cells that stably express CMO1 wild-type, but not in cells that express the CMO1 mutant or vector alone. These findings have implications for local vitamin A synthesis in the lung, especially during systemic vitamin A insufficiency and may also help to explain, in part, the mechanism underlying the increased lung cancer risk upon ß-carotene supplementation in smokers.

[Prospective study on magnetic resonance-guided focused ultrasound surgery for symptomatic uterine fibroid: short-term follow up].

OBJECTIVE: To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS) in treatment of symptomatic uterine leiomyoma among Chinese reproductive age women. METHODS: From April 2010 to April 2012, 80 premenopausal women with symptomatic leiomyoma volunteered to participate in this prospective study in Department of Outpatient of Peking Union Medical College Hospital. Among 23 reproductive aged patients with size of uterus less than 16th gestational weeks, 2.5 to 10 cm of diameter of myoma, less than 10 myomas and expressing symptoms clearly were treated by MRgFUS. Treatment data, non-perfused volume ratio (NPVR) and adverse events were recorded. After treatment, patients were followed up at 1 week, 1, 3, 6, 12 and 24 months, respectively. Patients at initial screening and each time of the follow-up filled out uterine fibroid symptoms quality of life (UFS-QOL), which include symptoms severity score (SSS) and health-related quality of life (HRQL). The volumes of leiomyoma and uterine were evaluated on MRI before and after the treatment (at 6 and 12 months, respectively). Before operation, routine blood test were performed on all patients, anemia patients at 3 months and 1 year after treatment were checked with blood test. RESULTS: (1) Treatment data and adverse events: the mean therapeutic temperature was (69 ± 7)°C, the mean treatment time was (144 ± 62) min, the mean NPVR was (62 ± 23)%. Adverse events included mild erythema(1/23), abdominal cramp (8/23), vaginal discharge (5/23), and leg numbness (4/23). (2) The rate of secondary surgery: one patient was treated by myoectomy and hysterectomy within one year following up and 4 patients chose surgical treatment during the second-year follow-up. (3) Volume change:the volumes of leiomyoma before the treatment and 6, 12 months after the treatment are 75.6(P25 = 43.8, P75 = 128.9), 52.3(P25 = 23.8, P75 = 111.2), 45.9(P25 = 26.3, P75 = 71.7) cm(3), respectively; and the volumes of uterine before the treatment and 6, 12 months after the treatment are 270.0 (P25 = 208.4, P75 = 390.3), 216.4 (P25 = 151.1, P75 = 290.0), 200.0 (P25 = 149.1, P75 = 267.6) cm(3), respectively. Both leiomyoma and uterine volumes decreased significantly after treatments (P < 0.01). (4) UFS-QOL change:the symptoms severity score (SSS) before the treatment and 3, 12 months after the treatment are (34 ± 13), (22 ± 11), (19 ± 12), which decreased significantly (P < 0.01). The health-related quality of life (HRQL) before the treatment and 3, 12 months after the treatment are (74 ± 15), (82 ± 13), (89 ± 10), which increased dramatically (P < 0.01). (5) Hemoglobin (HGB) change: eleven patients suffered from anemia before treatments, the mean HGB before treatment was (87 ± 6) g/L and were (106 ± 14) g/L 3 months after treatment, (112 ± 10) g/L 12 months after treatment. The HGB was increased significantly after treatments (P < 0.01). CONCLUSIONS: MRgFUS is a safe and effective non-invasive management for symptomatic uterine leiomyoma in short-term follow up. But there is additional treatment ratio after MRgFUS.

Bioinformatics Analysis of the Prognostic Significance of VPS16 in Hepatocellular Carcinoma and Its Role in Drug Screening.

Background: Vacuolar protein sorting 16 (VPS16) overexpression was recently considered related to cancer growth and drug resistance; however, little is known about whether VPS16 plays a vital role in liver hepatocellular carcinoma (LIHC). Methods: The TIMER2 online database was used to analyze the expression of VPS16 in pancancer, and the Xena Browser was used to explore the correlation between VPS16 expression level and survival time. R language was used to test the survival data of 374 LIHC cases in the TCGA database. DESeq2 was used for differentially expressed gene (DEG) analysis. The HPA database was used to verify the expression level of VPS16 in LIHC. The clusterProfiler package was used to analyze functions and related signaling pathways via GO/KEGG enrichment analysis. Drug sensitivity analysis and molecular docking technology were used to screen the most sensitive drugs targeting VPS16 molecules. Results: Pancancer analysis showed that VPS16 was highly expressed in various tumors, especially in LIHC. With the increase in the T stage and grade of LIHC, the expression level of VPS16 was also increased. The expression of VPS16 was negatively correlated with the overall survival of LIHC patients. The stage can be used as an independent prognostic factor. A total of 63 sensitive drugs were found, and 19 drugs were displaying strong molecular binding energy with VPS16. Conclusion: VPS16 may be a potential biomarker for the diagnosis and prognosis of LIHC. Drugs targeting VPS16 may be used in the treatment of LIHC in the future.

[Study on ischiospinous ligament fixation in treatment of stage III pelvic organ prolapse].

OBJECTIVE: To evaluate the safety and efficacy of ischiospinous ligament fixation in treatment of stage III pelvic organ prolapse (POP). METHODS: Between March 2007 and December 2009, 65 patients with stage III POP who underwent ischiospinous ligament fixation in Peking Union Medical College Hospital were enrolled in this study. Among 21 cases complicated with stress urinary incontinence (SUI) underwent transobturator tension-free vaginal tape (TVT-O) concomitantly. Clinical parameter associated with perioperation, objective and subjective successful rate and complication were recorded. RESULTS: The mean operating time was (71 ± 22) min and the mean blood loss was (93 ± 40) ml. No intraoperative blood transfusion and viscera injury cases were observed. All patients were able to recover spontaneous micturition. Two cases experienced pelvic hematoma with diameter of 7 cm, after conservative treatment, they all recovered later. The objective success rate was 100% at 6 weeks follow-up by POP-Q scoring. And 46.2% (30/65) were followed up at range of 1 - 3 years, recurrence rate were 10% (3/30), and however, no operation were needed. At median of 20 months, all patients were followed up by telephone, the subjective successful rate was 95.4% (62/65). At 6 weeks after operation, 6.2% (4/65) patients suffered from lower back pain and right thigh pain, visual analogue scale of pain was at range of 3 to 5, which relieved gradually after treatment and disappeared totally within 2 years. The rate of suture exposure was 10% (3/30), the new urinary incontinence 4.6% (3/65), and the new dyspareunia 12.5% (3/24). CONCLUSIONS: Ischiospinous ligament fixation is a safe and efficacious management.

[Prospective study on total pelvic reconstruction surgery with Prosima in the treatment of pelvic organ prolapse stage III].

OBJECTIVE: To evaluate the safety and efficacy of total pelvic reconstruction surgery with Prosima in treatment of pelvic organ prolapse (POP) stage III. METHODS: From July 2010 to December 2011, 31 patients with POP stage III undergoing total pelvic reconstruction surgery with Prosima were enrolled in this prospective study. Among two cases complicated with stress urinary incontinence underwent transobturator tension-free vaginal tape concomitantly with total pelvic reconstruction surgery with Prosima. Clinical parameters during peri-operation were recorded and compared. Pelvic organ prolapse quantitative examination (POP-Q) and anatomic improvement in these patients after surgery were analyzed. Comparisons of pelvic floor impact questionnaire-short form 7 (PFIQ-7) and pelvic organ prolapse-urinary incontinence sexual questionnaire-short form 12 (PISQ-12) in these patients before and after surgery were used to evaluate quality of life and quality of sexual life. RESULTS: The mean operating time was (55 ± 13) minutes, mean blood loss was (66 ± 25) ml. No severe intraoperative complications were observed. All patients were able to recover spontaneous micturation within 5 days. Two cases experienced pelvic hematoma with diameters less than 7 cm, and resolved later. Another case was urinary tract infection. At the median follow-up 6 months (1 - 15 months), the rate of anatomic success defined as the leading vaginal edge above the hymen was 94% (29/31). There were significant improvements in Aa, Ba, Ap, Bp, and C (P < 0.01) by POP-Q. Two patients showed recurrent prolapse at 3 months and 1 year after surgery, without the need of further operation. The median score of post-operative PFIQ-7 was 0 point at 6 months and 0 point at 12 months after operation, respectively, which were significantly lower than that of 50 points pre-operation (P < 0.01). And there was no significant difference in the average score of PISQ-12 before and after surgery [(30 ± 6) points versus (31 ± 4) points] (P > 0.05). The rate of mesh exposure was 16% (5/31), all the 5 cases occurred within 6 months and was cut in clinic. There was no case of de novo urinary incontinence and de novo dyspareunia. CONCLUSIONS: Pelvic reconstruction surgery with Prosima is safe and efficacy in treatment of POP stage III. It could improve quality of life remarkably without influence on sexual quality of life.