Association between visceral adipose tissue area and infertility: a cross-sectional analysis.

RESEARCH QUESTION: Is intra-abdominal fat obesity associated with infertility? DESIGN: This study analysed data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women enrolled. The participants were divided into two groups: infertility and non-infertility. Differences between the two groups were analysed using a weighted Student's t-test or Mann-Whitney U-test for continuous variables, or a weighted chi-squared test for categorical data. Visceral adipose tissue area (VATA) was assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility. RESULTS: Log VATA was significantly higher in the infertility group compared with the non-infertility group (P < 0.001). After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with increased prevalence of female infertility (OR = 2.453, 95% CI 1.278-4.792). Subgroup analyses showed this association in individuals aged <35 years (P = 0.002), Mexican-Americans (P = 0.033), non-hypertensive individuals (P = 0.013) and non-diabetic individuals (P = 0.003). CONCLUSIONS: An enlarged VATA is associated with increased risk of infertility. The direct effect of VATA on female infertility needs to be clarified further to provide a basis for future prevention and treatment of female infertility.

Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer.

Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

Axial Symptoms and Spinal-pelvic Parameters After Degenerative Lumbar Spondylolisthesis.

Context: Degenerative spondylolisthesis (DS) is a prevalent degenerative condition affecting the lumbar spine. Local spinal parameters play a pivotal role in surgical complications and in the QoL that adults with spinal deformities experience. Treatment can effectively alleviate radicular symptoms, but it doesn't significantly mitigate postoperative axial symptoms (AS). Objective: The study intended to investigate the correlation between postoperative axial symptoms (AS) and spinal-pelvic parameters for patients with DS of the lumbar spine. Design: The research team conducted a prospective cohort study. Setting: The study took place at the Huai'an Hospital of Huai'an City in the Huai'an District of Huai'an City in JiangSu Province, China. Participants: Participants were 120 patients with DS who had been admitted to the department of orthopedics at the hospital between January 2016 and December 2022 and 120 healthy volunteers during the same period. Intervention: The research team created two groups, each with 120 participants: (1) the intervention group with DS who received posterior laminar decompression + pedicle-screw internal fixation + intervertebral-space bone grafting and fusion, and (2) the control group, the healthy volunteers. Outcome Measures: The research team: (1) measured both group's spinal-pelvic parameters at baseline and at 6 months postintervention, (2) evaluated both group's motor functions at baseline and at 6 months postintervention, using the Japanese Orthopedic Association (OAS) scale and the Oswestry Disability Index (ODI), (3) examined the intervention group's postoperative AS, and (4) analyzed the correlation between the intervention group's spinal-pelvic parameters and its postoperative AS and motor function. Results: At 6 months postintervention, the intervention group's spinal-pelvic parameters-lumbar lordosis (LL) and sacral slope (SS) were significantly lower-and-pelvic incidence (PI), pelvic tilt (PT), thoracic kyphosis (TK), segmental lumbar lordosis (SLL), and sagittal vertical axis (SVA) were significantly higher than those of the control group (all P = .000). The intervention group's JOA and ODI scores were significantly lower than those of the control group postintervention (both P = .000). Postintervention compared to the non-AS group, the AS group's LL (P = .000), PI (P = .000), and SS (P = .020) were significantly lower and PT (P = .002), TK (P = .000), SLL (P = .002), and SVA (P = .000) were significantly higher. Postoperative AS was negatively correlated with LL, PI, SS, and positively correlated with PT, TK, SLL, and SVA (all P = .000). The JOA and ODI scores were positively correlated with LL, PI, and SS, and negatively correlated with PT, TK, SLL, and SVA (all P = .000). Conclusions: Postoperative AS in patients with DS is significantly correlated with spinal-pelvic parameters, providing convincing evidence for the evaluation of postoperative dysfunction. However, generalizing to other patients is limited due to the small sample size, which might have resulted in bias in spinal-pelvic parameters. Hence, ongoing trials with large samples are warranted.

Prospects of marine-derived compounds as potential therapeutic agents for glioma.

CONTEXT: Glioma, the most common primary malignant brain tumour, is a grave health concern associated with high morbidity and mortality. Current treatments, while effective to some extent, are often hindered by factors such as the blood-brain barrier and tumour microenvironment. This underscores the pressing need for exploring new pharmacologically active anti-glioma compounds. METHODS: This review synthesizes information from major databases, including Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer Link and relevant books. Publications were selected without date restrictions, using terms such as 'Hymenocrater spp.,' 'phytochemical,' 'pharmacological,' 'extract,' 'essential oil' and 'traditional uses.' General web searches using Google and Yahoo were also performed. Articles related to agriculture, ecology, synthetic work or published in languages other than English or Chinese were excluded. RESULTS: The marine environment has been identified as a rich source of diverse natural products with potent antitumour properties. CONCLUSIONS: This paper not only provides a comprehensive review of marine-derived compounds but also unveils their potential in treating glioblastoma multiforme (GBM) based on functional classifications. It encapsulates the latest research progress on the regulatory biological functions and mechanisms of these marine substances in GBM, offering invaluable insights for the development of new glioma treatments.

Integrated single-cell and bulk RNA sequencing analysis identifies a cancer-associated fibroblast-related gene signature for predicting survival and therapy in gastric cancer.

As the dominant component of the tumor microenvironment, cancer-associated fibroblasts (CAFs), play a vital role in tumor progression. An increasing number of studies have confirmed that CAFs are involved in almost every aspect of tumors including tumorigenesis, metabolism, invasion, metastasis and drug resistance, and CAFs provide an attractive therapeutic target. This study aimed to explore the feature genes of CAFs for potential therapeutic targets and reliable prediction of prognosis in patients with gastric cancer (GC). Bioinformatic analysis was utilized to identify the feature genes of CAFs in GC by performing an integrated analysis of single-cell and transcriptome RNA sequencing using R software. Based on these feature genes, a CAF-related gene signature was constructed for prognostic prediction by LASSO. Simultaneously, survival analysis and nomogram were performed to validate the prognostic predictive value of this gene signature, and qRT-PCR and immunohistochemical staining verified the expression of the feature genes of CAFs. In addition, small molecular drugs for gene therapy of CAF-related gene signatures in GC patients were identified using the connectivity map (CMAP) database. A combination of nine CAF-related genes was constructed to characterize the prognosis of GC, and the prognostic potential and differential expression of the gene signature were initially validated. Additionally, three small molecular drugs were deduced to have anticancer properties on GC progression. By integrating single-cell and bulk RNA sequencing analyses, a novel gene signature of CAFs was constructed. The results provide a positive impact on future research and clinical studies involving CAFs for GC.

Geographic and Sociodemographic Variations in Prevalence of Mental Health Symptoms Among US Youths, 2022.

Objectives. To assess geographic and sociodemographic variations in prevalence of mental health symptoms among US youths. Methods. We analyzed data from the Household Pulse Survey, phases 3.5 and 3.6, between June 1 and November 14, 2022. The sample included 103 296 households with an estimated 190 017 youths younger than 18 years. We defined mental health symptoms based on parental responses and estimated prevalence by state and subgroups, including race/ethnicity, parental education, household income, housing tenure, household food sufficiency, and health insurance coverage. All analyses incorporated sampling weight. Results. An estimated 34.5% (95% confidence interval [CI] = 33.7%, 35.3%) of youths had parent-reported mental health symptoms. The prevalence of symptoms varied across states, ranging from 27.9% (95% CI = 23.8%, 32.0%) in Florida to 46.4% (95% CI = 41.9%, 50.9%) in New Hampshire. We observed variations by subgroup, with youths in households that did not pay rent reporting a prevalence of 43.8% (95% CI = 39.3%, 48.4%) and those experiencing food insufficiency reporting a prevalence of 56.0% (95% CI = 50.9%, 61.2%). Conclusions. There is an urgent need for attention to mental health challenges among youths, taking into account geographic and sociodemographic variations. (Am J Public Health. 2023;113(10):1116-1119. https://doi.org/10.2105/AJPH.2023.307355).

Comparison of State-of-the-Art Neural Network Survival Models with the Pooled Cohort Equations for Cardiovascular Disease Risk Prediction.

BACKGROUND: The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown. METHODS: In this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models' internal and external discrimination power and calibration. RESULTS: The training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD. CONCLUSIONS: We demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs.

Large scale rice germplasm screening for identification of novel brown planthopper resistance sources.

Rice (Oryza sativa L.) is a staple food crop globally. Brown planthopper (Nilaparvata lugens Stål, BPH) is the most destructive insect that threatens rice production annually. More than 40 BPH resistance genes have been identified so far, which provide valuable gene resources for marker-assisted breeding against BPH. However, it is still urgent to evaluate rice germplasms and to explore more new wide-spectrum BPH resistance genes to combat newly occurring virulent BPH populations. To this end, 560 germplasm accessions were collected from the International Rice Research Institute (IRRI), and their resistance to current BPH population of China was examined. A total of 105 highly resistant materials were identified. Molecular screening of BPH resistance genes in these rice germplasms was conducted by developing specific functional molecular markers of eight cloned resistance genes. Twenty-three resistant germplasms were found to contain none of the 8 cloned BPH resistance genes. These accessions also exhibited a variety of resistance mechanisms as indicated by an improved insect weight gain (WG) method, suggesting the existence of new resistance genes. One new BPH resistance gene, Bph44(t), was identified in rice accession IRGC 15344 and preliminarily mapped to a 0-2 Mb region on chromosome 4. This study systematically sorted out the corresponding relationships between BPH resistance genes and germplasm resources using a functional molecular marker system. Newly explored resistant germplasms will provide valualble donors for the identification of new resistance genes and BPH resistance breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01416-x.

Intestinal fibrosis classification in patients with Crohn's disease using CT enterography-based deep learning: comparisons with radiomics and radiologists.

OBJECTIVES: Accurate evaluation of bowel fibrosis in patients with Crohn's disease (CD) remains challenging. Computed tomography enterography (CTE)-based radiomics enables the assessment of bowel fibrosis; however, it has some deficiencies. We aimed to develop and validate a CTE-based deep learning model (DLM) for characterizing bowel fibrosis more efficiently. METHODS: We enrolled 312 bowel segments of 235 CD patients (median age, 33 years old) from three hospitals in this retrospective study. A training cohort and test cohort 1 were recruited from center 1, while test cohort 2 from centers 2 and 3. All patients performed CTE within 3 months before surgery. The histological fibrosis was semi-quantitatively assessed. A DLM was constructed in the training cohort based on a 3D deep convolutional neural network with 10-fold cross-validation, and external independent validation was conducted on the test cohorts. The radiomics model (RM) was developed with 4 selected radiomics features extracted from CTE images by using logistic regression. The evaluation of CTE images was performed by two radiologists. DeLong's test and a non-inferiority test were used to compare the models' performance. RESULTS: DLM distinguished none-mild from moderate-severe bowel fibrosis with an area under the receiver operator characteristic curve (AUC) of 0.828 in the training cohort and 0.811, 0.808, and 0.839 in the total test cohort, test cohorts 1 and 2, respectively. In the total test cohort, DLM achieved better performance than two radiologists (*1 AUC = 0.579, *2 AUC = 0.646; both p < 0.05) and was not inferior to RM (AUC = 0.813, p < 0.05). The total processing time for DLM was much shorter than that of RM (p < 0.001). CONCLUSION: DLM is better than radiologists in diagnosing intestinal fibrosis on CTE in patients with CD and not inferior to RM; furthermore, it is more time-saving compared to RM. KEY POINTS: • Question Could computed tomography enterography (CTE)-based deep learning model (DLM) accurately distinguish intestinal fibrosis severity in patients with Crohn's disease (CD)? • Findings In this cross-sectional study that included 235 patients with CD, DLM achieved better performance than that of two radiologists' interpretation and was not inferior to RM with significant differences and much shorter processing time. • Meaning This DLM may accurately distinguish the degree of intestinal fibrosis in patients with CD and guide gastroenterologists to formulate individualized treatment strategies for those with bowel strictures.

COM33 suppresses carboplatin-induced epithelial-mesenchymal transition via inhibition of Twist1 in ovarian cancer.

Despite favorable responses to platinum-based chemotherapy in ovarian cancer (OC), chemoresistance is still a major cause of treatment failure. Hence, we develop a novel synthetic agent, COM33, to relieve the chemoresistance caused by carboplatin. The anti-cancerous effects of the combination of COM33 and carboplatin on OC are evaluated by cell viability, wound healing, and transwell invasion assays. A mechanistic investigation is carried out by using RNA-Seq analysis and then verified by western blot analysis and immunofluorescence microscopy. The safety and efficacy in vivo are evaluated using SKOV3 tumor-bearing nude mice. Results show that the co-administration of COM33 enhances the inhibitory effects of carboplatin on cancer cell viability, migration, and invasion in vitro and tumor growth in vivo. Furthermore, COM33 suppresses the carboplatin-induced epithelial-mesenchymal transition (EMT) by inhibiting the ERK signaling pathway. Additionally, we show that Twist1, the effector of the ERK signaling pathway, participates in carboplatin-induced EMT and is also inhibited by COM33. Our data show that the combination of carboplatin with COM33 is beneficial for chemotherapy against OC, which may be a potential novel anti-tumor strategy.

Modified FOLFOXIRI With or Without Cetuximab as Conversion Therapy in Patients with RAS/BRAF Wild-Type Unresectable Liver Metastases Colorectal Cancer: The FOCULM Multicenter Phase II Trial.

PURPOSE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI (mFOLFOXIRI: 5-fluorouracil/folinic acid, oxaliplatin, irinotecan) as conversion therapy in a two-group, nonrandomized, multicenter, phase II trial in patients with initially technically unresectable colorectal liver-limited metastases (CLM) and BRAF/RAS wild-type. PATIENTS AND METHODS: Patients were enrolled to receive cetuximab (500 mg/m2 ) plus mFOLFOXIRI (oxaliplatin 85 mg/m2 , irinotecan 165 mg/m2 , folinic acid 400 mg/m2 , 5-fluorouracil 2,800 mg/m2 46-hour infusion, every 2 weeks) (the cetuximab group) or the same regimen of mFOLFOXIRI alone (the control group), in a 2:1 ratio allocation. The primary endpoint was the rate of no evidence of disease (NED) achieved. Secondary endpoints included resection rate, objective response rate (ORR), survival, and safety. RESULTS: Between February 2014 and July 2019, 117 patients were registered for screening at six centers in China, and 101 of these were enrolled (67 cetuximab group, 34 control group). The rate of NED achieved was 70.1% in the cetuximab group and 41.2% in the control group (difference 29.0%; 95% confidence interval [CI], 9.1%-48.8%; p = .005). Patients in the cetuximab group had improved ORR (95.5% vs. 76.5%; difference 19.1%; 95% CI, 17.4%-36.4%; p = .010) compared with those in control group. Progression-free survival and overall survival showed the trend to favor the cetuximab group. The incidence of grade 3 and 4 adverse events was similar in the two groups. CONCLUSION: Addition of cetuximab to mFOLFOXIRI improved the rate of NED achieved. This combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable CLM. IMPLICATIONS FOR PRACTICE: This trial evaluated the addition of cetuximab to a modified FOLFOXIRI as conversion therapy in a phase II trial in patients with initially technically unresectable colorectal liver-limited metastases and BRAF/RAS wild-type. The rate of no evidence of disease achieved was 70.1% in the cetuximab plus modified FOLFOXIRI group and 41.2% in the modified FOLFOXIRI group. Objective response rates, overall survival, and progression-free survival were improved in the cetuximab group when compared with the modified FOLFOXIRI group. Addition of cetuximab to modified FOLFOXIRI increased the rate of no evidence of disease achieved, and this combination could be an option of conversion regimen for molecularly selected patients with initially technically unresectable colorectal liver-limited metastasis.

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception.

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

Using 17ß-estradiol heparin-poloxamer thermosensitive hydrogel to enhance the endometrial regeneration and functional recovery of intrauterine adhesions in a rat model.

Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E2-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E2-HP hydrogel on the recovery of IUA. Our results showed that E2-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E2-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E2-HP hydrogel can effectively transfer E2 into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.

Impact of pelvic dimensions on anastomotic leak after anterior resection for patients with rectal cancer.

AIM: The impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL. METHODS: A total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans. RESULTS: Univariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67-0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65-0.74]), but didn't reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A. CONCLUSION: Pelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

Elevated ovarian pentraxin 3 in polycystic ovary syndrome.

PURPOSE: Pentraxin 3 (PTX3) plays a crucial role in cumulus expansion and fertilization. The ovarian PTX3 level in polycystic ovary syndrome (PCOS) remains uncertain. In the present study, we investigated the follicular PTX3 levels and found the influence of reproductive hormones on ovarian PTX3 concentration. METHODS: This study was based on 204 healthy-weight women (102 PCOS and 102 normal ovulating subjects) undergoing in vitro fertilization (IVF). Follicular fluid (FF) was collected during oocyte retrieval. The PTX3 levels and other hormone levels in FF samples were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The PTX3 level in the follicle was significantly higher in the healthy-weight PCOS women than controls. Positive correlations were found between ovarian PTX3 level and the existence of PCOS, cycle length, basal LH to FSH ratio and TT in serum, antral follicle count, and ovarian insulin and androgen level, and inverse correlations with the basal serum PRL and ovarian SHBG. In multivariant linear regression analysis, the presence of PCOS diagnosis, participants' basal LH to FSH ratio, and ovarian androstenedione level were the main predictors of ovarian PTX3 level among the enrolled subjects. CONCLUSION: Elevated ovarian PTX3 level supports the low-grade chronic inflammatory state in the follicles of PCOS. The existence of PCOS, disturbed pituitary gland, and ovarian hyperandrogenism might also be related to this state of low-grade chronic inflammation and could be a subject of further study.

The casein kinase 2α promotes the occurrence polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment.

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis.

BACKGROUND: As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism. METHODS: MIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. RESULTS: MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. CONCLUSIONS: MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.

Alleviation of drought stress and the physiological mechanisms in Citrus cultivar (Huangguogan) treated with methyl jasmonate.

The role of exogenous methyl jasmonate (MeJA) in alleviating drought stress was investigated on Huangguogan. Except for intercellular CO2 concentration, MeJA had little effect on net photosynthetic rate, stomatal conductance, and transpiration rate under drought stress. Compared with drought stress, MeJA significantly alleviated the decrease of chlorophyll content. However, chlorophyll a/b ratio was significantly increased. MeJA significantly increased proline and soluble sugar contents, significantly decreased the O2 -· and H2O2 levels, and increased SOD and POD activities. In addition, the MDA content of drought stress was the highest of all treatments. MeJA significantly reduced MDA content in drought-stressed Huangguogan leaves. Although the Ascorbic acid (AsA) contents of 500 and 1000 mg L-1 MeJA treatments were lower than that of 250 mg L-1 MeJA, but all concentration of MeJA treatments delayed the decline of AsA content. Therefore, MeJA could induce drought stress tolerance by increasing the osmotic adjustment substances and antioxidant activities.

Baseline and early 3D-CUBE volume reconstruction of locally advanced rectal cancer to predict tumor response after neoadjuvant chemotherapy.

PURPOSE: To explore whether volumetric measurements of 3D-CUBE sequences based on baseline and early treatment time can predict neoadjuvent chemotherapy (NCT) efficacy of locally advanced rectal cancer (LARC). MATERIAL AND METHOD: 73 patients with LARC were enrolled from February 2014 to January 2018. All patients underwent MRIs during the baseline period before NCT (BL-NCT) and the first month of NCT (FM-NCT), and tumor volume (TV) was measured using 3D-CUBE, and tumor volume reduction (TVR) and tumor volume reduction rate (TVRR) were calculated. In addition, tumor invasion depth, tumor maximal length, range of tumor involvement in the circumference of intestinal lumen and distance from inferior part of tumor to the anal verge were measured using baseline high-spatial-resolution T2-weighted MRIs. All patients were categorized into sensitive and insensitive groups based on post-surgical pathology after completion of the full courses of NCT. The receiver operating characteristic (ROC) curve was used to analyze the value of different MRI parameters in predicting efficacy of NCT. RESULTS: Statistically significant differences in TV of BL-NCT, TVR and TVRR from BL-NCT to FM-NCT were detected between sensitive and insensitive groups (P < 0.05, respectively). The areas under the curves (AUC) of ROC of TVR and TVRR in predicting efficacy of NCT (0.890 [95% CI, 0.795∼0.951], 0.839 [95% CI, 0.735∼0.915]) were significantly better than that of TV (0.660 [95% CI, 0.540∼0.767]) (P < 0.05, respectively). CONCLUSION: Reconstruction of 3D-CUBE volume in the first month of NCT is necessary, and both TVR and TVRR can be used as early predictors of NCT efficacy.

Radiomics-Based Pretherapeutic Prediction of Non-response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

OBJECTIVE: The aim of this study was to investigate whether pretherapeutic, multiparametric magnetic resonance imaging (MRI) radiomic features can be used for predicting non-response to neoadjuvant therapy in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively enrolled 425 patients with LARC [allocated in a 3:1 ratio to a primary (n = 318) or validation (n = 107) cohort] who received neoadjuvant therapy before surgery. All patients underwent T1-weighted, T2-weighted, diffusion-weighted, and contrast-enhanced T1-weighted MRI scans before receiving neoadjuvant therapy. We extracted 2424 radiomic features from the pretherapeutic, multiparametric MR images of each patient. The Wilcoxon rank-sum test, Spearman correlation analysis, and least absolute shrinkage and selection operator regression were successively performed for feature selection, whereupon a multiparametric MRI-based radiomic model was established by means of multivariate logistic regression analysis. This feature selection and multivariate logistic regression analysis was also performed on all single-modality MRI data to establish four single-modality radiomic models. The performance of the five radiomic models was evaluated by receiver operating characteristic (ROC) curve analysis in both cohorts. RESULTS: The multiparametric, MRI-based radiomic model based on 16 features showed good predictive performance in both the primary (p < 0.01) and validation (p < 0.05) cohorts, and performed better than all single-modality models. The area under the ROC curve of this multiparametric MRI-based radiomic model achieved a score of 0.822 (95% CI 0.752-0.891). CONCLUSIONS: We demonstrated that pretherapeutic, multiparametric MRI radiomic features have potential in predicting non-response to neoadjuvant therapy in patients with LARC.