[Curcumol reverses temozolomide resistance in glioma cells by regulating the UTX/MGMT axis].

OBJECTIVE: To explore the mechanism through which curcumol reverses primary drug resistance in glioma cells. METHODS: The inhibitory effect of 10, 20, and 40 µg/mL curcumol were observed in human glioma cell lines A172 and U251. UTX-overexpressing glioma cells constructed by lentiviral transfection were treated with curcumol (40 µg/mL), temozolomide (TMZ; 10 µg/mL), or both, and the changes in cell viability, clone formation capacity and apoptosis were assessed using MTT assay, cell clone formation experiment, and flow cytometry; UTX activity in the cells was determined using a UTX detection kit, and the enrichment of UTX and H3K27me3 in the MGMT promoter region was detected with ChiP-qPCR. The protein expressions in glioma cells were detected using Western blotting and immunohistochemistry. In a nude mouse model bearing glioma xenografts, the effects of curcumol (20 mg/kg), TMZ (20 mg/kg) and their combination on tumor growth and expressions of UTX, H3K27me3 and MGMT were evaluated. RESULTS: Curcumol significantly inhibited the proliferation (P<0.05) and promoted apoptosis of cultured glioma cells (P<0.01). Curcumol, but not TMZ, produced significant inhibitory effect on tumor growth in the tumor-bearing mice (P<0.01). Curcumol significantly inhibited UTX activity and increased the expression level of H3K27me3 protein in the glioma cells. UTX overexpression obviously decreased H3K27me3 protein expression and reversed the effects of curcumol on glioma cell proliferation and apoptosis (P<0.01). Curcumol reduced the enrichment of UTX and H3K27me3 in the MGMT promoter region (P<0.05) and decreased MGMT protein expression, which was reversed by UTX overexpression. In both the in vivo and in vitro experiments, curcumol combined with TMZ significantly increased H3K27me3 protein expression in the glioma cells, reduced the expression of its downstream target gene MGMT, and enhanced TMZ sensitivity of the glioma cells. CONCLUSION: Curcumol can enhance glioma cell sensitivity to TMZ by regulating the UTX/MGMT axis.

[A Meta-analysis of the predictive value of peripheral blood neutrophil to lymphocyte ratio in mortality of patients with acute paraquat poisoning].

Objective: To evaluate the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) in mortality of patients with acute paraquat poisoning. Methods: In March 2022, all literatures about the studies on NLR assessing the mortality of patients with acute paraquat poisoning were searched in the National Library of Medicine PubMed, Embase, Cochrane Library Database, Web of Science, CNKI, Wanfang Medicine Database, Weipu Database, China Biology Medicine disc (SinoMed). The data updated by March 2022, without the limitation of languages. Two researchers extracted literature information independently and conducted literature quality evaluation using QUADAS-2. And the data extracted from the literatures were analyzed with Stata 16 software. Results: A total of 9 studies were included in this Meta-analysis, including 967 patients. And the Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 0.77 (95%CI: 0.72-0.82, P<0.05), 0.83 (95%CI: 0.74-0.90, P<0.05), 4.63 (95%CI: 2.99-7.15, P<0.05), 0.27 (95%CI: 0.22-0.34, P<0.05) and 17.06 (95%CI: 10.22-28.48, P<0.05), and the area under the curve (AUC) of the summary receiver operator characteristics curve (SROC) was 0.85 (95%CI: 0.81-0.88) . Conclusion: NLR has predictive value in 30-day mortality of patients with acute paraquat poisoning.

Insulin Resistance-Varying Associations of Adiposity Indices with Cerebral Perfusion in Older Adults: A Population-Based Study.

OBJECTIVES: Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance. DESIGN: This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study. SETTING AND PARTICIPANTS: The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans. METHODS: We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis. RESULTS: Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted ß-coefficients and 95%CI: -1.76; -3.25, -0.27 and -1.77; -3.25, -0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05). CONCLUSION: Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.

[Smith-Kingsmore syndrome caused by MTOR gene variation: 2 cases and literature review].

Objective: To investigate the clinical manifestations and genetic features of 2 children with Smith-Kingsmore syndrome caused by MTOR gene variation and review the literature. Methods: The clinical data of 2 children carrying MTOR gene variant, diagnosed at Xi'an Children's Hospital from April 2018 to April 2021, were retrospectively summarized."MTOR"and"Smith-Kingsmore syndrome"were used as key words to search at China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and OMIM up to August 2021. The characteristics of MTOR gene variation and the clinical phenotype of children with Smith-Kingsmore syndrome were summarized. Results: Two children were both females, aged 1.5 years and 2 years respectively, the onset age were both in infancy. They both had developmental delay, megalencephaly and abnormal face. Both whole exome sequencing revealed a de novo heterozygous missense variant in MTOR gene. One case carried c.5395G>A (p.Glu1799Lys) and the other case carried c.7234G>C (p.Asp2412His). There was no literature of MTOR gene variation in Chinese. So far, a total of 45 cases were reported worldwide with detailed clinical information. Eleven variations in MTOR gene were involved, which were all heterozygous missense mutations. Among them, p.Glu1799Lys was the most common sites (28 cases,62%). Another case carried c.7234G>C (p.Asp2412His) was not reported before. Summarizing the 47 cases (including these 2 cases), 46 cases had developmental delay or intellectual disability, 9 cases had developmental regression,42 cases had megalencephaly, 30 cases had facial malformation,16 cases had hypotonia, 17 cases had autism spectrum disorders, 3 cases had hyperactivity, 3 cases had obsessive compulsive disorder, 13 cases had eye diseases, 11 cases had cutaneous vascular malformation, and 9 cases had hypoglycemia. Conclusions: The main clinical features of Smith-Kingsmore syndrome include megalencephaly, developmental delay or intellectual disability, and facial malformation, which can be combined with epilepsy, autism spectrum disorder, hypotonia, hypoglycemia and so on. The variation of MTOR gene is the cause of Smith-Kingsmore syndrome.

Standard diffusion-weighted, intravoxel incoherent motion, and dynamic contrast-enhanced MRI of musculoskeletal tumours: correlations with Ki67 proliferation status.

AIM: To determine whether quantitative parameters derived from conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlate with the Ki67 proliferation status in musculoskeletal tumours. MATERIALS AND METHODS: Twenty-eight patients with musculoskeletal tumours diagnosed via surgical specimen histological analysis who underwent standard DWI, IVIM, and DCE were reviewed retrospectively. The mean standard DWI (apparent diffusion coefficient [ADC]), IVIM (pure diffusion coefficient [D], pseudo-diffusion coefficient [D∗] and perfusion fraction [ƒ]), and DCE (volume transfer constant [Ktrans], rate constant [Kep], and extravascular extracellular volume fraction [Ve]) parameters were measured and correlated with the Ki67 index. The Ki67 value was categorised as high (>20%) or low (≤20%). RESULTS: The ADC and D values correlated negatively with the Ki67 index (r=-0.711∼-0.699, p<0.001), whereas the Ktrans and Kep values correlated positively with the Ki67 index (r=0.389-0.434, p=0.021, 0.041). The ADC and D values were lower (p<0.001), whereas the Ktrans and Kep values were higher (p=0.011, 0.005) in musculoskeletal tumours with a high Ki67 status than in those in a low status. The ADC and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.953), which is statistically bigger than the AUC of Ktrans and Kep (0.784 and 0.802, respectively). CONCLUSION: ADC, D, Ktrans, and Kep correlate with the Ki67 index. ADC and D are the strongest quantitative parameters for predicting Ki67 status.

[Effects of climate changes on the distribution of Rhipicephalus microplus in China].

OBJECTIVE: To identify the environmental factors affecting the geographical distribution of Rhipicephalus microplus in China, and to examine the impact of climate changes on the distribution of R. microplus in China. METHODS: The national and international publications pertaining to the geographical distribution of R. microplus in China were retrieved, and the geographical location was extracted. The suitable habitats of R. microplus and the dominant environmental factors affecting the distribution of suitable habitats of R. microplus were predicted in China based on the geographical data and environmental variables using the ArcGIS 10.7 software and the maximum entropy model. RESULTS: Among the main climatic factors affecting the geographical distribution of R. microplus in China, the factors contributing more than 10% to the suitable habitats of R. microplus mainly include the annual mean precipitation (38.2%), the average temperature of the coldest quarter (28.4%) and the precipitation of the driest month (14.2%). The current suitable habitats of R. microplus were mainly found in southern China, and the high-, medium- and low-suitable areas accounted for 8.6%, 13.1% and 10.5% of the total land area of China, respectively. The suitable habitats of R. microplus were predicted to increase by 399 800 km2 in China using the maximum entropy model under the RCP 4.5 emissions scenario in 2070, and the emerging suitable habitats were mainly distributed in Gansu Province, Ningxia Hui Autonomous Region, Qinghai Province, Hebei Province, Shaanxi Province, Liaoning Province, Inner Mongolia Autonomous Region, Shandong Province, Sichuan Province and Tibeten Autonomous Region. In addition, the suitable habitats of R. microplus were predicted to show an overall expansion towards northward from present to 2070. CONCLUSIONS: Climate changes affect the distribution of suitable habitats of R. microplus in China, and annual mean precipitation may be a key factor affecting the distribution of suitable habitats of R. microplus.

Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis.

OBJECTIVE: Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. METHODS: Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by CCK-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. RESULTS: In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1ß-treated NPCs. Mechanistically, QUE suppressed IL-1ß induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. CONCLUSIONS: Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

CT and MRI features of giant cell tumours with prominent aneurysmal bone cysts in the extremities: a comparison with primary aneurysmal bone cysts.

AIM: To test the hypothesis that computed tomography (CT) and magnetic resonance imaging (MRI) could help distinguish between giant cell tumours with prominent aneurysmal bone cysts (GABCs) and primary aneurysmal bone cysts (PABCs) of the extremities. MATERIALS AND METHODS: CT and MRI features of 13 patients with GABCs and 13 patients with PABCs in the extremities were analysed retrospectively. The ages and sex of the patients were also recorded. Independent-samples t-tests were used for continuous variables and Fisher's exact tests were used for categorical variables to compare the differences between the two groups. Diagnostic accuracy, sensitivity, and interobserver agreement were calculated. RESULTS: The average age of patients with GABCs (38.2±15.8 years) was higher than that of patients with PABCs (19.3±12.7 years; p=0.003). The transverse/longitudinal diameter ratio was different between GABCs (0.8±0.3) and PABCs (0.6±0.2; p=0.007). Subchondral bone involvement (92.3% versus 30.8%, p=0.004) and deep lobulation (38.5% versus 0%, p=0.039) were more likely to be noted in patients with GABCs. Surrounding blood vessels were identified in six cases of PABCs (6/13), but not in GABCs (p=0.015). The following characteristics were suggestive of GABCs, older patient age, higher transverse/longitudinal diameter ratio, subchondral bone involvement, and deep lobulation indicated a sensitivity of 84.6%, 76.9%, 75%, and 100%, and a specificity of 84.6%, 69.2%, 90%, and 61.9%, respectively. Conversely, surrounding blood vessels were suggestive of PABCs, with a sensitivity of 46.2% and specificity of 100%. The concordance between the two readers was moderate to nearly perfect. CONCLUSION: Age, subchondral bone involvement, lobulation, transverse/longitudinal diameter ratio, and surrounding blood vessels can be used to distinguish GABCs from PABCs.

Follow-up management strategy for patients undergoing peritoneal dialysis during novel coronavirus pneumonia epidemic.

OBJECTIVE: The study aimed to explore the best follow-up management strategy for patients undergoing peritoneal dialysis (PD) during the novel coronavirus pneumonia (NCP) epidemic. PATIENTS AND METHODS: Patients undergoing PD who were followed up during the NCP epidemic by our hospital were enrolled in this study. Because of the need to control the epidemic, a follow-up system was established during the epidemic period, with WeChat, QQ, and the telephone as the main methods of communication. Outpatient and emergency follow-ups were carried out to ensure the safety of dialysis and the prevention and control of the epidemic. The follow-up strategy included response measures related to the epidemic situation, prevention of peritonitis related to PD, water and salt control, exercise guidance, and psychological care. According to the patient's condition, the appointment system was implemented, with one consulting room and one process for each patient. The emergency patients were isolated in accordance with the epidemic situation. RESULTS: Since January 2020, among the 580 patients undergoing PD who were followed up in our department and their families, none had NCP infection. During the epidemic period, the standard hemoglobin level and the inpatient rate decreased. Complications related to PD, such as peritonitis, cardiovascular complications caused by volume overload, and pulmonary infection, did not significantly increase, and the withdrawal rate and mortality rate decreased compared with those in the same period last year. CONCLUSIONS: The patient follow-up strategy during the epidemic period had a significant positive effect on preventing and controlling the epidemic. Furthermore, during the epidemic period, encouraging patients and caregivers to pay attention to protection at home, avoid going out, strengthen self-management, and other measures were beneficial to the control of kidney disease itself, which is worth promoting. The close relationship between doctors and patients during the epidemic had a positive effect on the occurrence of complications related to patients undergoing PD.

Supracondylar humeral fractures in children: American Academy of Orthopaedic Surgeons appropriate use criteria versus actual management in a teaching hospital.

PURPOSE: The objective of this study was to explore whether there were any differences between the theoretical recommendations for children's supracondylar humeral fractures (CSHF) according to the American Academy of Orthopaedic Surgeons (AAOS) guidelines and the treatments they actually received in our institution. METHODS: We retrospectively reviewed the medical charts and radiographs of all CSHFs at our hospital between January 2015 and December 2018. In all, 301 children meeting our inclusion criteria were identified and evaluated using the AAOS-Appropriate Use Criteria (AUC) application for supracondylar humerus fractures. Actual treatment was then compared with the treatment recommended by the AUC. RESULTS: Actual operative management was undertaken in 0/58 (0%) Gartland type I fractures, 61/108 (56.5%) type II fractures and 98/135 (72.6%) type III fractures. Actual nonoperative management was undertaken in 58/58 (100%) Gartland type I fractures, 47/108 (43.5%) type II fractures and 37/135 (27.4%) type III fractures. Surgeon decisions for nonoperative treatment were in agreement with the AUC recommendations 100% of the time, whereas surgeon decisions for surgery matched the AUC recommendations 65.4% of the time. Predictors of actual operative management were age (p =0.003), fracture classification (p =0.000), associated orthopaedic injury requiring surgery (p =0.025) and anterior humeral line (AHL) not intersecting the capitellum (p =0.008). CONCLUSION: We found low agreement between actual treatments and the AUC-recommended 'appropriate' treatments. The AUC favoured operative intervention more frequently largely on the basis of fracture classification while we emphasized age, fracture classification, associated orthopaedic injury requiring surgery and alignment of the AHL with the capitellum in our operative decision-making process. LEVEL OF EVIDENCE: Therapeutic Level II.

LncRNAp21 promotes osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis by the Wnt/ß-catenin signaling pathway.

OBJECTIVE: The aim of this study was to explore the promoting effect of long non-coding ribonucleic acid p21 (lncRNAp21) on the osteogenic differentiation of mesenchymal stem cells in the rat model of osteoporosis (OP) through the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: A total of 30 healthy female rats were selected and randomly divided into three groups, including the lncRNAp21 group, OP model group (model group) and normal group. Rats in the lncRNAp21 group were given a certain quantity of lncRNAp21 inhibitors for gavage. Rats in the model group were regularly given 0.9% NaCl for gavage every day after the removal of bilateral ovaries. Meanwhile, rats in the normal group were fed normally without any changes. Bone mineral density (BMD) was measured after 12 weeks of modeling. The levels of procollagen type I N-terminal propeptide (PINP), serum estradiol (E2), osteocalcin (OC), bone alkaline phosphatase (BALP), C-terminal cross-linking telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the bone and serum of rats were measured by enzyme-linked immunosorbent assay (ELISA). Besides, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were adopted to detect the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues, respectively. RESULTS: Compared with the normal group and lncRNAp21 group, the serum level of E2 in the model group decreased significantly (p<0.05). BMD and phosphorus (P) content in the model group were both markedly lower than those of the normal group and lncRNAp21 group. However, calcium (Ca) content was remarkably higher than that of the normal group and lncRNAp21 group (p<0.05). The serum levels of bone resorption markers (including TRACP-5b and CTX) in the model group were prominently higher than those of the normal group (p<0.05). However, the levels of the two markers in the lncRNAp21 group were significantly lower than the model group (p<0.05). Additionally, bone formation markers (including OC, PINP and BALP) in the serum of rats in the model group were notably higher than those in the normal group and lncRNAp21 group (p<0.05). QRT-PCR and Western blotting results revealed that the mRNA and protein expressions of Wnt1 and ß-catenin in bone tissues of the model group were markedly lower than those of the normal group. However, the mRNA and protein expressions of Wnt1 and ß-catenin in the lncRNAp21 group were remarkably higher than the model group (p<0.05). CONCLUSIONS: Low expression of lncRNAp21 activates the Wnt/ß-catenin signaling pathway by increasing E2 secretion, eventually stimulating bone formation and increasing osteogenic differentiation of mesenchymal stem cells in OP model rats.

[Spontaneous focal lamina cribrosa defect in glaucoma and its relationship with nonprogressive glaucomatous neuropathy].

Objective: To investigate the relationship between the spontaneous focal lamina cribrosa (LC) defect and the progression of visual field defect (VFD) in primary open-angle glaucoma (POAG). Methods: Case-control study. The patients who were diagnosed as POAG with at least 5 visual field results had been collected from June 2018 to January 2019 at Beijing Tongren Hospital Affiliated to Capital Medical University. Serial imaging by swept source optical coherence tomography B-Scan of the optic discs were acquired at the end of the follow-up and LC defects status were reviewed. Intraocular pressure, mean defects of visual field, central corneal thickness and axis length were recorded in the follow-up duration. Eyes were classified as having either progressive or nonprogressive VFD, and associating factors were evaluated by χ(2) or Fisher's test, mixed-effect model analysis and multivariate Logistical regression analysis. Results: A total of 32 subjects (64 eyes) were enrolled in the study with mean age of (47±14) years, the group consisted of 17 males and 15 females. Fourty-five eyes showed nonprogressive VFD. LC defects were more common in eyes without (28/45) rather than with progressive VFD (5/19) (χ(2)=6.896, P=0.009). Eyes with nonprogressive VFD showed longer axis length[(26.82±1.34) mm vs. (25.79±1.44) mm; t=6.589, P=0.013] and wider LC defects diameter[211 (165-326) µm vs. 114 (106-156) µm; Z=4.797, P=0.042]. Multivariate Logistic regression analysis revealed that the presence of LC defect was significantly associated with nonprogressive VFD (odds ratio=0.217, P=0.012). There were 7 subjects with asymmetry VFD and the incedence of LC defects without progression (7/7) is higher than fellow eye with progression (1/7, P=0.002). There was only one patient with progressive VFD showed one LC defect with an smaller diameter (169 µm) than that in the contralateral eyes with stable VFD (269 µm). Conclusions: LC defects are more common in eyes with nonprogressive VFD. Spontaneous LC defects are associated with nonprogressive glaucomatous defects and could be a protective factor for POAG. (Chin J Ophthalmol, 2019, 55:338-346).

Chondrosarcoma in a paediatric population: a study of 247 cases.

PURPOSE: The aims of present study are to clarify the follow questions: 1) what constitutes paediatric chondrosarcoma?; 2) what are the effects of the demographic and tumour characteristics on survival in patients with paediatric chondrosarcoma?; 3) which prognostic factors of paediatric chondrosarcoma differ from those of the adult population, which have been reported previously? METHODS: Paediatric patients who were diagnosed with chondrosarcoma were searched for using the case listing session protocol of the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 databases (1973 to 2014). The extracted demographic information includes: age, race, gender, year of diagnosis, tumour sites, tumour histological subtype, grade, stage and treatment. RESULTS: A total of 247 paediatric chondrosarcoma patients were extracted and included in our present study. We find that the paediatric patients have significantly better survival rates than the adult patients. The year of diagnosis, tumour sites, tumour histological subtype, grade, stage and surgery received are independent prognostic factors for the survival rate of paediatric chondrosarcoma patients, but race, gender and age are not. CONCLUSION: The paediatric chondrosarcoma patients have better survival rates than the adults. Paediatric patients with a diagnosis at an early age, tumour site at the vertebral column and pelvis/sacrococcyx, myxoid variants, high grade, distant stage and who did not have surgery have a poorer prognosis than patients with a diagnosis at a later age, tumour site at limbs, head and base, chondrosarcoma not otherwise specified, lower grade, localized stage and who received surgery. LEVEL OF EVIDENCE: II -Prognostic Study.

Effects of methotrexate on the quality of oocyte maturation in vitro.

Methotrexate (MTX), an antifolate drug, is widely used for clinical treatment of malignancies and ectopic pregnancy. Many studies have documented that MTX has strong side-effects on rapidly dividing somatic cells. However, its side-effects on female reproductive cells have not been widely reported. Combined with in vitro culture, two-photon fluorescence imaging and three-dimensional reconstruction, this study analyzed the effects of MTX on oocyte maturation time, chromosome arrangement, karyotype, spindle morphology, and the localization of microtubule organizing centers (MTOCs). Compared with a control group (84%), the rate of germinal vesical breakdown in the MTX group dropped to 73% (P < 0.05). The rate of the first polar body extrusion in the MTX group (53%) was also below the control group (63%; P < 0.05). The rate of abnormal chromosomal arrangement in the MTX group was 60%, but 24% in the control group (P < 0.05). The matured oocyte karyotypes showed 20 univalents in both control and MTX groups, while point-shaped DAPI signals were detected in the MTX group. The rate of abnormal spindle in the MTX group was 49%, but 17% in the control group (P < 0.05). MTOCs in oocytes with normal spindles concentrated at the poles, while MTOCs in oocytes with abnormal spindles were scattered around the poles or in the ooplasm. MTX changes the structures of chromosomes and spindles, potentially by interfering with DNA methylation. The above results indicate a basis for understanding negative effects of MTX on oocyte maturation quality, and provide information for the clinical application of MTX in female patients.

Evaluation on the impact of spontaneous reperfusion on cardiac muscle of acute myocardial infarction by three-dimensional speckle tracking imaging.

OBJECTIVE: To explore the effect of spontaneous reperfusion (SR) on three-dimensional myocardial strain in patients with acute anterior myocardial infarction by three-dimensional speckle tracking imaging (3D-STI) technology. PATIENTS AND METHODS: Patients diagnosed with acute anterior myocardial infarction during 2013 to 2016 were consecutively selected and divided into SR group and non-spontaneous reperfusion (Non-SR) group based on whether there was SR. Patients in both groups received direct percutaneous coronary intervention (PCI) in time window. Baseline information, patency rates of culprit vessel, durations of operation, intraoperative non-reflow phenomenon ratios, and thrombolysis in myocardial infarction (TIMI) blood flows after reperfusion of patients in each group were recorded. Hospital stays of patients were compared between the two groups. Before discharge, left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) were measured. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of left ventricular (LV) were also detected by 3D-STI, so as to assess movement situations of ventricular wall and cardiac muscle in occlusive blood vessel distribution area. LVEF, LVEDd and various 3D-STI parameters were reexamined and compared one year after discharge. RESULTS: There were no significant differences between the Non-SR group and the SR group regarding the patency rate of culprit vessel, duration of operation, intraoperative non-reflow phenomenon ratio, TIMI blood flow after reperfusion, and LVEDd (p>0.05). Both LVEF before discharge and LV three-dimensional strain indexes of the SR group, were clearly higher than those of the Non-SR group (p<0.05). After one-year follow-up, the SR group had a remarkably lower LVEDd than the Non-SR group (p<0.05). LVEF of the SR group was overtly higher than that of the Non-SR group (p<0.05). LV three-dimensional strain indexes were also distinctly higher in the SR group than in the Non-SR group (p<0.05). There were good correlations between GLS, GRS, GCS and LVEF (r values were -0.620, -0.674 and 0.723, respectively). CONCLUSIONS: SR can improve nosocomial and long-term LV remodeling in patients with acute anterior myocardial infarction, and 3D-STI is able to assess ventricular remodeling after myocardial infarction.

NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of all-trans retinoic acid via targeting RDH16 in malignant glioma.

Polycomb group (PcG) proteins play an important role in development and stem cell maintenance, and their dysregulation have been closely linked to oncogenesis and cancer stem cell phenotypes. Here, we found that nervous system polycomb 1 (NSPc1) was highly expressed in stem cell-like glioma cells (SLCs). Knockdown of NSPc1 in SLCs resulted in impaired neurosphere formation and self-renewal abilities, down-regulated expression of stemness markers such as NESTIN, CD133 and SOX2, and decreased capacity to propagate subcutaneous xenografts. In contrast, glioma cells overexpressing NSPc1 exhibited a stem cell-like phenotype, up-regulated expression of stemness markers NESTIN, CD133 and SOX2, and an enhanced capacity to propagate subcutaneous xenografts. Furthermore, we identified that NSPc1 epigenetically repressed the expression of retinol dehydrogenase 16 (RDH16) by directly binding to a region upstream (-1073 to -823) of the RDH16 promoter. Next, we confirmed that RDH16 is a stemness suppressor that partially rescues SLCs from the NSPc1-induced increase in neurosphere formation. Finally, we showed that ATRA partly reversed the NSPc1-induced stemness enhancement in SLCs, through mechanisms correlated with an ATRA-dependent decrease in the expression of NSPc1. Thus, our results demonstrate that NSPc1 promotes cancer stem cell self-renewal by repressing the synthesis of ATRA via targeting RDH16 and may provide novel targets for glioma treatment in the future.

Comparative transcriptomic analysis of key genes involved in flavonoid biosynthetic pathway and identification of a flavonol synthase from Artemisia annua L.

The regulatory mechanism of flavonoids, which synergise anti-malarial and anti-cancer compounds in Artemisia annua, is still unclear. In this study, an anthocyanidin-accumulating mutant callus was induced from A. annua and comparative transcriptomic analysis of wild-type and mutant calli performed, based on the next-generation Illumina/Solexa sequencing platform and de novo assembly. A total of 82,393 unigenes were obtained and 34,764 unigenes were annotated in the public database. Among these, 87 unigenes were assigned to 14 structural genes involved in the flavonoid biosynthetic pathway and 37 unigenes were assigned to 17 structural genes related to metabolism of flavonoids. More than 30 unigenes were assigned to regulatory genes, including R2R3-MYB, bHLH and WD40, which might regulate flavonoid biosynthesis. A further 29 unigenes encoding flavonoid biosynthetic enzymes or transcription factors were up-regulated in the mutant, while 19 unigenes were down-regulated, compared with the wild type. Expression levels of nine genes involved in the flavonoid pathway were compared using semi-quantitative RT-PCR, and results were consistent with comparative transcriptomic analysis. Finally, a putative flavonol synthase gene (AaFLS1) was identified from enzyme assay in vitro and in vivo through heterogeneous expression, and confirmed comparative transcriptomic analysis of wild-type and mutant callus. The present work has provided important target genes for the regulation of flavonoid biosynthesis in A. annua.

[Relationship between myocardial microRNA-30a expression and myocardial fibrosis in rats post myocardial infarction].

OBJECTIVE: To explore the potential role and mechanism of microRNA(miR)-30a in myocardial fibrosis after myocardial infarction (MI). METHODS: Rats were randomly divided into 1 week MI group (n=11), 2 weeks MI group (n=13) and 4 weeks MI group (n=15) by applying random number table after left anterior descending coronary artery ligation. Rats in Sham group were examined at respective time points (n=16). Heart function was monitored by echocardiography. Myocardial collagen volume fraction (CVF) was determined on Masson stained sections. Myocardial expression of collagen Ⅰ and Ⅲ was determined by immunohistochemistry. The myocardial mRNA level of miR-30a, TGF-ß1 and CTGF were detected by real time-quantitative PCR analysis. The myocardial protein levels of TGF-ß1 and CTGF were measured by Western blot analysis. RESULTS: The LVEDD ((8.37±0.58) mm) and LVESD ((6.12±0.82) mm) in 4 weeks MI group were significantly higher than those in Sham group ((6.08±0.57) mm, (4.17±0.60) mm), all P<0.01. The FS ((27.0±3.9) %) and LVEF ((51.0±6.3) %) in 4 weeks MI group were significantly lower than those in Sham group ((47.0±2.1) %, (82.0±2.3)%), all P<0.01. The level of myocardial CVF in 1 week MI group, 2 weeks MI group and 4 weeks MI group were significantly higher than in Sham group (all P<0.01) in a time-dependent manner. The level of myocardial collagen Ⅰ and Ⅲ was increased gradually from 1 week to 4 weeks post MI compared with Sham group (all P<0.01). The collagen Ⅰ/Ⅲ ratio was similar between 1 week MI group and Sham group (P=0.58), however, which was significantly higher in 2 weeks MI group and 4 weeks MI group compared with Sham group (all P<0.01), and the ratio was significantly higher in 4 weeks MI group than 2 weeks MI group (P<0.01). The level of miR-30a was significantly and gradually reduced in all MI groups compared with Sham group (all P<0.01). The mRNA and protein levels of TGF-ß1 and CTGF were significantly and gradually increased after MI compared with Sham group (all P<0.001). CONCLUSIONS: Our results indicate that overexpression of miR-30a after MI might be a potential strategy for suppressing myocardial fibrosis by modulating the mRNA and protein levels of TGF-ß1 and CTGF.

Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT

Purpose. To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). Methods. We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. Results. Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). Conclusion. DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness (AU)

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Early evaluation of targeted therapy effectiveness in non-small cell lung cancer by dynamic contrast-enhanced CT.

PURPOSE: To study the feasibility and clinical value of dynamic contrast-enhanced (DCE) computed tomography (CT) for early evaluation of targeted therapy efficacy in non-small cell lung cancer (NSCLC). METHODS: We measured tumor diameter, peak height (PH), time to peak (TP), tumor mass-aortic peak height ratio (M/A), and blood perfusion (BP) in 20 patients with advanced NSCLC using DCE-CT before and 7 days after treatment. Therapy efficacy was assessed with conventional CT 4-6 weeks post-treatment. RESULTS: Patients were grouped into those with partial response (PR), stable disease (SD), and progressive disease (PD) according to the therapy efficacy assessment at 4-6 weeks post-treatment. The PR group primary tumor diameter (P = 0.0007) and BP (P = 0.0225) were reduced at 7 days post-treatment; the SD group DCE-CT value changes were not significant. The PD group M/A (P = 0.0443) and BP (P = 0.0268) were increased 7 days post-treatment. The BP decrease group had significantly longer progression-free survival than the BP increase group (median, 54 vs. 6 weeks). CONCLUSION: DCE-CT can evaluate targeted therapy efficacy at 7 days post-treatment. Decreased primary tumor diameter and BP indicate tumor sensitivity to therapy; increased BP with unchanged tumor diameter suggests the tumor is not sensitive to therapy. Reduced BP suggests treatment effectiveness.