Emergence of aztreonam/avibactam and tigecycline-resistant Pseudomonas putida group Co-producing blaIMP-1, blaAFM-4 and blaOXA-1041 with a novel sequence type ST268 in Southwestern China.

OBJECTIVES: The emergence of carbapenem-resistant Pseudomonas putida (CRPP) has raised public awareness. This study investigated two strains from the Pseudomonas putida group that were resistant to carbapenem, tigecycline, and aztreonam-avibactam (ATM-AVI), with a focus on their microbial and genomic characteristics. METHODS: We assessed the antibiotic resistance profile using broth dilution, disk diffusion, and E-test methods. Efflux pump phenotype testing and real-time quantitative PCR were employed to evaluate efflux pump activity in tigecycline resistance, while polymerase chain reaction was utilized to detect common carbapenem genes. Additionally, whole-genome sequencing was performed to analyze genomic characteristics. The transferability of blaIMP-1 and blaAFM-4 was assessed through a conjugation experiment. Furthermore, growth kinetics and biofilm formation were examined using growth curves and crystal violet staining. RESULTS: Both strains demonstrated resistance to carbapenem, tigecycline, and ATM-AVI. Notably, NMP can restore sensitivity to tigecycline. Subsequent analysis revealed that they co-produced blaIMP-1, blaAFM-4, tmexCD-toprJ, and blaOXA-1041, belonging to a novel sequence type ST268. Although they were closely related on the phylogenetic tree, they exhibited different levels of virulence. Genetic environment analysis indicated variations compared to prior studies, particularly regarding the blaIMP-1 and blaAFM-4 genes, which showed limited horizontal transferability. Moreover, it was observed that temperature exerted a specific influence on their biological factors. CONCLUSION: We initially identified two P. putida ST268 strains co-producing blaIMP-1, blaAFM-4, blaOXA-1041, and tmexCD-toprJ. The resistance to tigecycline and ATM-AVI can be attributed to the presence of multiple drug resistance determinants. These findings underscore the significance of P. putida as a reservoir for novel antibiotic resistance genes. Therefore, it is imperative to develop alternative antibiotic therapies and establish effective monitoring of bacterial resistance.

Carbapenem-Resistant Enterobacter cloacae Complex in Southwest China: Molecular Characteristics and Risk Factors Caused by NDM Producers.

Purpose: The isolation rate of carbapenem-resistant Enterobacter cloacae complex (CREC) is continuously increasing. The aims of this study were to investigate the molecular characteristics and risk factors associated with CREC infections. Methods: Bacterial species were identified using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonik GmbH, Bremen, Germany), and the hsp60 gene was utilized for further typing. Antimicrobial susceptibilities were assessed through the MicroScan WalkAway 96 Plus system (Siemens, Germany) and the microbroth dilution method. Antimicrobial resistance genes were screened through polymerase chain reaction (PCR), while the homologous relationship was assessed using multilocus sequence typing (MLST). Conjugation experiments were performed to verify whether the plasmid could be transferred. Additionally, logistic regression model was employed to analyze risk factors for CREC infections. Results: 32 strains of CREC bacteria were isolated during the study, yet only 20 were retained for preservation. While the isolates demonstrated resistance to the majority of antibiotics, they exhibited high sensitivity to polymyxin B and tigecycline. All isolates carried the blaNDM resistance gene, including 13 blaNDM-1 isolates and 7 blaNDM-5 isolates. MLST homology analysis revealed the presence of seven known ST types and one new ST type. Conjugation experiments confirmed that 13 isolates were capable of transferring the blaNDM resistance gene to Escherichia coli strain EC600. Single-factor analysis identified multiple primary risk factors for CREC infection, but multivariate analysis did not reveal independent risk factors. Conclusion: This study investigates the molecular characteristics and risk factors associated with CREC infections. The detection rate of CREC strains in our hospital is continuously rising and homology analysis suggested that strains might spread in our hospital, emphasizing the importance of implementing effective preventive measures to control the horizontal transmission of plasmid-mediated antimicrobial resistance genes.

OCT imaging of endolymphatic hydrops in mice: association with hearing loss.

BACKGROUND: The etiology of Ménière's disease (MD) is still not completely clear, but it is believed to be associated with endolymphatic hydrops (EH), which is characterized by auditory functional disorders. Vasopressin injection in C57BL/6J mice can induce EH and serve as a model for MD. Optical Coherence Tomography (OCT) has shown its advantages as a non-invasive imaging method for observing EH.AimInvestigating the relationship between hearing loss and EH to assist clinical hearing assessments and indicate the severity of hydrops. METHODS: C57BL/6J mice received 50 µg/100g/day vasopressin injections to induce EH. Auditory function was assessed using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE). OCT was used to visualize the cochlea. RESULT: OCT observed accumulation of fluid within the scala media in the cochlear apex. ABR showed significant hearing loss after 4 weeks. DPOAE revealed low-frequency hearing loss at 2 weeks and widespread damage across frequencies at 4 weeks. CONCLUSION: The development of hearing loss in mouse models of MD is consistent with EH manifestations.SignificanceThis study demonstrates the possibility of indirectly evaluating the extent of EH through auditory assessment and emphasizes the significant value of OCT for imaging cochlear structures.

Role of efflux pumps, their inhibitors, and regulators in colistin resistance.

Colistin is highly promising against multidrug-resistant and extensively drug-resistant bacteria clinically. Bacteria are resistant to colistin mainly through mcr and chromosome-mediated lipopolysaccharide (LPS) synthesis-related locus variation. However, the current understanding cannot fully explain the resistance mechanism in mcr-negative colistin-resistant strains. Significantly, the contribution of efflux pumps to colistin resistance remains to be clarified. This review aims to discuss the contribution of efflux pumps and their related transcriptional regulators to colistin resistance in various bacteria and the reversal effect of efflux pump inhibitors on colistin resistance. Previous studies suggested a complex regulatory relationship between the efflux pumps and their transcriptional regulators and LPS synthesis, transport, and modification. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), 1-(1-naphthylmethyl)-piperazine (NMP), and Phe-Arg-ß-naphthylamide (PAßN) all achieved the reversal of colistin resistance, highlighting the role of efflux pumps in colistin resistance and their potential for adjuvant development. The contribution of the efflux pumps to colistin resistance might also be related to specific genetic backgrounds. They can participate in colistin tolerance and heterogeneous resistance to affect the treatment efficacy of colistin. These findings help understand the development of resistance in mcr-negative colistin-resistant strains.

Analysis of characteristic features in ultrasound diagnosis of fetal limb body wall complex during 11-13+6 weeks.

BACKGROUND: Limb body wall complex (LBWC) is a fatal malformation characterized by major defects in the fetal abdominal or thoracic wall, visceral herniation, significant scoliosis or spina bifida, limb deformities, craniofacial deformities, and umbilical cord abnormalities (short or absent umbilical cord). Early diagnosis of this condition is of great clinical significance for clinical intervention and pregnancy decision-making. With the rapid development of fetal ultrasound medicine, early pregnancy (11-13+6 wk) standardized prenatal ultrasound examinations have been widely promoted and applied. AIM: To explore the value of prenatal ultrasound in the diagnosis of fetal LBWC syndrome during early pregnancy. METHODS: The ultrasonographic data and follow-up results of 18 cases of fetal LBWC diagnosed by prenatal ultrasound during early pregnancy (11-13+6 wk) were retrospectively analyzed, and their ultrasonographic characteristics were analyzed. RESULTS: Among the 18 fetuses with limb wall abnormalities, there were spinal dysplasia (18/18, 100%), varying degrees of thoracoschisis and gastroschisis (18/18, 100%), limb dysplasia in 6 cases (6/18, 33%), craniocerebral malformations in 4 cases (4/18, 22%), thickening of the transparent layer of the neck in 5 cases (5/18, 28%), and umbilical cord abnormalities in 18 cases (18/18, 100%), single umbilical artery in 5 cases. CONCLUSION: Prenatal ultrasound in early pregnancy can detect LBWC as early as possible, and correct prenatal evaluation provides important guidance value for pregnancy decision-making and early intervention.

Ultrasonic visualization technique for anatomical and functional analyses of the sciatic nerve in rats.

Background and objective: Ultrasound has been widely used in the diagnosis and minimally invasive treatment of peripheral nerve diseases in the clinic, but there is still a lack of feasibility analysis in rodent models of neurological disease. The purpose of this study was to investigate the changes in the cross-sectional area of the sciatic nerve of different genders and body weights and to explore the effectiveness and reliability of an ultrasound-guided block around the sciatic nerve in living rats. Methods: Using ultrasound imaging anatomy of the sciatic nerve of rats, the cross-sectional area of the sciatic nerve in rats of different genders from 6 to 10 weeks old was calculated, and then analyzed its correlation with body weight. Further analyses were conducted through behavioral and cadaveric studies to evaluate the feasibility of ultrasound-guided perineural injection of the sciatic nerve in rats. Results: We first reported that the sciatic nerve cross-sectional area of rats was increased with age (F = 89.169, P < 0.001), males had a higher sciatic nerve cross-sectional area than females (F = 60.770, P < 0.001), and there was a positive correlation with body weight (rMale = 0.8976, P < 0.001; rFemale = 0.7733, P < 0.001). Behavioral observation of rats showed that the lower extremity complete block rate was 80% following the administration of drugs around the sciatic nerve under ultrasound guidance and staining with methylene blue occurred in all sciatic nerves and surrounding muscles and fascia using 20 ultrasound-guided injections. Conclusions: Ultrasound visualization technology can be used as a new auxiliary evaluation and intervention therapy for animal models of peripheral nerve injury, and will provide overwhelming new references for the basic research of neurological diseases.

Epidemiology, antifungal susceptibility, risk factors, and mortality of persistent candidemia in adult patients in China: a 6-year multicenter retrospective study.

BACKGROUND: Data on persistent candidemia (PC), a recognized complication of candidemia, are lacking in China. This study aimed to investigate the clinical characteristics and risk factors for the mortality of PC among adults in China. METHODS: This 6-year retrospective study analyzed the prevalence, species distribution, antifungal susceptibility, risk factors, and patient mortality of PC among adults in three regional tertiary teaching hospitals in China from 2016 to 2021. We collected electronic laboratory records data of PC and non-PC patients and used the Student test or Mann-Whitney U test for a retrospective study. Logistic regression was used to identify risk factors associated with persistent candidemia. RESULTS: The definition of PC was fulfilled by 36 patients (13.7%, 36/263). The mean age of the patients was 59.9 years (60 years for patients with PC; 59.8 years for those with non-PC; P > 0.05) and 131 (60.1%) were men [16 with PC (44.4%), 115 with non-PC (63.2%), P < 0.05]. The mean annual incidence was 0.15/1000 admissions (including PC 0.03/1000 admissions vs. non-PC 0.12/1000 admissions, P < 0.05). Candida parapsilosis (14/36, 38.9%) and Candida albicans (81/182, 44.5%) were the predominant pathogens in patients with PC and non-PC, respectively. Most isolates were susceptible to flucytosine (99.0%) and amphotericin B (99.5%), and the activity of antifungal agents against Candida species was not statistically significantly different between patients with PC and non-PC (P > 0.05). The 30-day mortality rate was 20.2% (16.7% with PC vs. 20.9% with non-PC, P > 0.05). Multivariable regression analysis showed that use of broad-spectrum antibiotics (odds ratio (OR), 5.925; 95% confidence interval (CI), 1.886-18.616, P = 0.002), fluconazole (OR, 3.389; 95% CI, 1.302-8.820, P = 0.012) and C. parapsilosis infection (OR, 6.143; 95% CI, 2.093-18.031, P = 0.001) were independent predictors of PC, sex (male) (OR, 0.199; 95% CI, 0.077-0.518, P = 0.001) was the protective factor for PC. Respiratory dysfunction (OR, 5.763; 95% CI, 1.592-20.864, P = 0.008) and length of hospital stay(OR, 0.925; 95% CI, 0.880-0.973, P = 0.002) were independent predictors of 30-day mortality in patients with non-PC. C. tropicalis bloodstream infection (OR, 12.642; 95% CI, 1.059-150.951; P = 0.045) was an independent predictor of 30-day mortality in patients with PC. CONCLUSIONS: The epidemiological data of patients with PC and non-PC were different in the distribution of Candida species, the mean annual incidence and independent predictors of 30-day mortality. Flucytosine and amphotericin B could be used as first-choice drugs in the presence of PC infections.

Neural basis of the attention bias during addiction stroop task in methamphetamine-dependent patients with and without a history of psychosis: an ERP study.

Background: Attentional bias plays an important role in sustaining various types of drug addiction. No prior studies examined methamphetamine (MA)-associated psychosis (MAP) relationships between ERP time course and performance on an addiction Stroop task in MA abusers. The aim of the present study was to determine whether MA abusers with (MAP+) or without (MAP-) psychosis exhibit alterations of the ERP during the addiction Stroop task. Methods: Thirty-one healthy controls (CTRL), 14 MAP-, and 24 MAP+ participants were recruited and completed the addiction Stroop task during EEG recording using 32 electrodes. Group variations were compared on measures of behavioral task performance and event-related potentials (ERP) of performance monitoring (N200, P300, N450). The Barratt impulsiveness scores were analyzed to investigate correlations with ERP changes. Results: MA-related word stimulus elicited a more negative N200 amplitude over left-anterior electrodes in MAP- abusers; furthermore, a positive association between the N200 amplitude and Barratt attentional scores and non-planning scores was observed, while no such differences were found in MAP+ abusers. There were no significant differences in reaction time (RT) and error rate between each group. Conclusion: This is the first study to examine psychosis relationships between ERP time course and performance on an addiction Stroop task in MA abusers with or without psychosis. These findings support the association between attentional bias measured by the MA addiction Stroop task and N200 component as well as indicate the possibility of using this cognitive task in combination with ERP technology to detect psychosis factors among abstinent MA abusers.

Corrigendum to 'Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/ß-catenin and MAPKs signaling pathways' [Genes & Diseases 9 (2022) 466-478].

[This corrects the article DOI: 10.1016/j.gendis.2020.07.014.].

Soil C, N and P stoichiometry in different forest stand types in the middle and lower reaches of the Beijiang River, China.

We examined the vertical distribution characteristics of soil organic carbon (C), total nitrogen (N), total phosphorus (P) and their ecological stoichiometric ratios in 0-80 cm soil profile under three forest stand types in the middle and lower reaches of the Beijiang River, including broad-leaved forest, coniferous forest, and mixed coniferous and broad-leaved forest. The results showed that soil C, N and P contents of the three forest stand types were 12.17-14.25, 1.14-1.31, and 0.27-0.30 g·kg-1, respectively. The contents of C and N decreased with the increases of soil depth. The content of C and N in each soil layer showed that coniferous and broad-leaved mixed forest > coniferous forest > broad-leaved forest. There was no significant difference in P content among the three stand types, and there was no obvious variation in the vertical profile. The soil C/N, C/P, and N/P of the three forest types were 11.2-11.3, 49.0-60.3, and 4.5-5.7, respectively. There was no significant difference in soil C/N among the three stand types. The highest soil C/P and N/P were found in the mixed forest. There was no interaction between soil depth and stand type in affecting soil C, N, P contents and their stoichiometric ratios. There was significant positive correlation between C and N, and between N and C/P in each stand type and soil layer. Soil C/P and N/P had stronger ecological indicating effects on stand types. The coniferous and broad-leaved mixed forest was strongly limited by P availability.

Comparisons of the diagnostic accuracy of the ultrasonic sign-score method and MRI for PA, PI and PP in high-risk gravid women: a retrospective study.

Background: The diagnosis and management of placenta accrete spectrum (PAS) is a great challenge to obstetricians. Ultrasound (US) and magnetic resonance imaging (MRI) are two main methods to detect PAS. MRI has high resolution, but the examination fee is expensive. US machine and examination fee is cheap, but the resolution is relatively low. Balancing the cost and accuracy for PAS diagnosis is very important. Methods: The ultrasonic sign-score method and MRI findings for 49 pregnant women at high risk of placental implantation were retrospectively analyzed. Inclusion criteria: (I) at high risk for PA as described in the Guidelines to Placenta Accreta Spectrum Disorders issued by the American College of Obstetricians and Gynecologists (ACOG) in 2018; (II) complete records of ultrasonic sign-scoring method and MRI data; (III) cesarean section; (IV) definite surgical and/or pathological findings. The results were validated by the gold-standard surgical or postoperative pathological findings, and the efficacy of the 2 imaging approaches in diagnosing placenta PAS was compared. Kappa test was used to analyze the consistency. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity. Results: The mean maternal age was 32.6±4.4 years. The mean gestational week was 35.9±2.0 weeks. The mean gravidity was 3.3±1.1. The surgical or histopathological findings revealed PA in 26, placenta increta (PI) in 19 and placenta percreta (PP) in 4 of the 49 women. The diagnosis accuracy of PA, PI, and PP was higher using the ultrasonic sign-scoring method than MRI (75.51%, 73.47%, and 97.96% vs. 61.22%, 57.14% and 91.84%, respectively). The areas under the ROC curve for the sensitivity and specificity of the ultrasonic sign-scoring method and MRI in the diagnosis of PA, PI, and PP were 0.757 [95% confidence interval (CI): 0.613, 0.868], 0.725 (95% CI: 0.579, 0.843), 0.989 (95% CI: 0.907, 1.000), and 0.607 (95% CI: 0.457, 0.743), 0.544 (95% CI: 0.395, 0.687), 0.614 (95% CI: 0.464, 0.749), respectively. Conclusions: Although the sensitivity and specificity were lower than 0.8, the ultrasonic sign-scoring method was still superior to MRI in the detection of PI and PP. US can be used to help identify high-risk gravid women.

Common gray matter loss in the frontal cortex in patients with methamphetamine-associated psychosis and schizophrenia.

BACKGROUND AND HYPOTHESIS: Methamphetamine (MA)-associated psychosis has become a public concern. However, its mechanism is not clear. Investigating similarities and differences between MA-associated psychosis and schizophrenia in brain alterations would be informative for neuropathology. STUDY DESIGN: This study compared gray matter volumes of the brain across four participant groups: healthy controls (HC, n = 53), MA users without psychosis (MA, n = 22), patients with MA-associated psychosis (MAP, n = 34) and patients with schizophrenia (SCZ, n = 33). Clinical predictors of brain alterations, as well as association of brain alterations with psychotic symptoms and attention impairment were further investigated. STUDY RESULTS: Compared with the HC, the MAP and the SCZ showed similar gray matter reductions in the frontal cortex, particularly in prefrontal areas. Moreover, a stepwise extension of gray matter reductions was exhibited across the MA - MAP - SCZ. Duration of abstinence was associated with regional volumetric recovery in the MAP, while this amendment in brain morphometry was not accompanied with symptom's remission. Illness duration of psychosis was among the predictive factors of regional gray matter reductions in both psychotic groups. Volume reductions were found to be associated with attention impairment in the SCZ, while this association was reversed in the MAP in frontal cortex. CONCLUSIONS: This study suggested MA-associated psychosis and schizophrenia had common neuropathology in cognitive-related frontal cortices. A continuum of neuropathology between MA use and schizophrenia was tentatively implicated. Illness progressions and glial repairments could both play roles in neuropathological changes in MA-associated psychosis.

TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9.

Bone morphogenetic protein 9 (BMP9), also named as growth differentiation factor 2 (GDF-2), is the strongest cytokine that promotes osteogenic differentiation in the BMP family, and has broad clinical application value. Nevertheless, the mechanism of BMP9 promotes osteogenic differentiation remain unclear. TAZ, a transcriptional co-activator, has great effects on cell proliferation, differentiation, and stem cell self-renewal. In this research, we investigated the effects of TAZ in BMP9-induced osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 (MSCs) and murine multi-lineage cell lines C2C12 and MEFs (MMCs) and explored its possible mechanisms. This study has found that BMP9 induces the expression of TAZ and promotes its nuclear translocation. Meanwhile, our study found that Ad-TAZ and TM-25659, a TAZ agonist, can enhance the osteogenic differentiation of MSCs and MMCs induced by BMP9. Conversely, Ad-si-TAZ and verteporfin, an inhibitor of TAZ, have the contradictory effect. Likewise, the promotion of TAZ to the BMP9-induced ectopic bone formation in vivo was confirmed by the subcutaneous transplantation of MSCs in nude mice. Furthermore, we have detected that TAZ might increase the levels of the phosphorylation of Smad1/5/8, p38, ERK1/2, and JNK induced by BMP9. Additionally, we also found that TAZ increased the total protein level of ß-catenin induced by BMP9. In summary, our results strongly indicated that TAZ will promote the osteogenic differentiation in MSCs and MMCs induced by BMP9 through multiple signal pathways.

Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/ß-catenin, PI3K/AKT and NF-κB signaling pathways.

Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the activity of Wnt/ß-catenin, PI3K/AKT and NF-κB signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/ß-catenin, PI3K/AKT and NF-κB to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS.

Nitazoxanide inhibits osteosarcoma cells growth and metastasis by suppressing AKT/mTOR and Wnt/ß-catenin signaling pathways.

Osteosarcoma (OS) is the most prevalent malignant bone tumor with poor prognosis. Developing new drugs for the chemotherapy of OS has been a focal point and a major obstacle of OS treatment. Nitazoxanide (NTZ), a conventional anti-parasitic agent, has got increasingly noticed because of its favorable antitumor potential. Herein, we investigated the effect of NTZ on human OS cells in vitro and in vivo. The results obtained in vitro showed that NTZ inhibited the proliferation, migration and invasion, arrested cell cycle at G1 phase, while induced apoptosis of OS cells. Mechanistically, NTZ suppressed the activity of AKT/mTOR and Wnt/ß-catenin signaling pathways of OS cells. Consistent with the results in vitro, orthotopic implantation model of 143B OS cells further confirmed that NTZ inhibited OS cells growth and lung metastasis in vivo. Notably, NTZ caused no apparent damage to normal cells/tissues. In conclusion, NTZ may inhibit tumor growth and metastasis of human OS cells through suppressing AKT/mTOR and Wnt/ß-catenin signaling pathways.

A Novel Modification of Copper (II) Phthalocyanine Particles towards Electrophoretic Displays.

Electrophoretic display (EPD) is a popular display technology in recent years. The core of the EPD is electrophoretic particles, and its Zeta potential has an important impact on EPDs. In this work, a method using pyrrolidine mono ionic liquid was proposed to improve the Zeta potential of electrophoretic particles: Copper (II) phthalocyanine pigment was modified with mono ionic liquid 1-Butyl-1-methylpyrrolidinium bromide. The characterization results show that the mono ionic liquid had been successfully coated on pigment particles. At the same time, the dispersion and stability of particles were improved. The modified Copper (II) phthalocyanine pigment could be stably dispersed in tetrachloroethylene for more than 20 days. The Zeta potential increased from 32.42 mV to 49.91 mV, increasing by 53.95%. Finally, the prepared blue electrophoretic particles were compounded with white titanium dioxide to prepare blue and white dual-color electrophoretic dispersion, and then an EPD cell was designed to test its performance. The results show that the prepared electrophoretic dispersion can realize reversible reciprocating motion. Therefore, because of the unique structure and properties of pyrrolidine mono ionic liquids, the blue nanoparticles prepared with pyrrolidine ionic liquids as charge control agents in this study can be used as excellent candidate materials for EPD.

Clinical Value of Three-Dimensional Transvaginal Ultrasound in Diagnosis of Endometrial Receptivity and Ovarian Function in Patients with Infertility.

Objective: A case-control study was conducted to explore the clinical value of three-dimensional transvaginal ultrasound in the diagnosis of endometrial receptivity (ER) and ovarian function in patients with infertility. Methods: A total of 308 infertile women treated in our hospital from March 2020 to June 2021 were enrolled as the observation group, and another 300 women of childbearing age who underwent physical examination in the same period were enrolled as the control group. The clinical value of three-dimensional transvaginal ultrasound in ER in patients with infertility was analyzed by comparing the classification of endometrial and subendometrial blood perfusion, endometrial AUC value and Pi value, and subendometrial AUC value and Pi value. According to the number of oocytes obtained, the patients were assigned into the normal response group (182 cases, ≥5 oocytes) and the low response group (126 cases, <5 oocytes). The levels of some hormones, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and FSH/LH, were measured. Transvaginal ultrasonography was performed to detect ovarian volume (OV), antral follicle count (AFC), and peak flow rate of the ovarian interstitial artery (PSV). The peak of end-diastolic flow velocity (EDV) and other indexes were analyzed. The correlation between FSH level, FSH/LH, and ultrasound indexes was analyzed, and the ROC curve was established to analyze the value of transvaginal Doppler ultrasound in evaluating ovarian reserve function and predicting ovulation. Results: There were significant differences in late proliferation type I and type III, ovulatory type II and type III (P < 0.05). There exhibited no significant difference in late proliferation type II, ovulation stage type I, and implantation window stage type I, type II, and type III (P > 0.05). Regarding the endometrial AUC and Pi values, the endometrial AUC and Pi values in the observation group were lower compared to the control group during late proliferation and ovulation (P < 0.05). There exhibited no significant difference in AUC and Pi (P > 0.05). Regarding the subintimal AUC and Pi values, the subintimal AUC and Pi values in the observation group were higher compared to the control group during late proliferation and ovulation (P < 0.05). There exhibited no significant difference in AUC and Pi during the implantation window (P > 0.05). There exhibited no significant difference in menarche age, age, body mass index, and menstrual cycle between the normal response group and the low response group (P > 0.05). The levels of EDV, OV, AFC, and PSV in the normal response group were higher compared to the low response group (P < 0.01). Compared with the low response group, the levels of FSH and FSH/LH in the normal response group were lower, but the levels of LH and E2 in the normal response group were higher (P < 0.05). The results of correlation analysis of FSH, FSH/LH, and ultrasound parameters between the normal response group and the low response group indicated that FSH was negatively correlated with E2, EDV, OV, AFC, and PSV in 308 infertile women (r = -0.817, -0.846, -0.707, -0.845, -0.911, P < 0.01), but it was positively correlated with FSH/LH (r = 0.714, P < 0.01). The ultrasound parameters of ovarian reserve function in the normal response group and the low response group were compared with the indexes that predicted ovulation. The results of ROC curve analysis indicated that the cutoff values of EDV, OV, AFC, and PSV were 4.141, 3.726, 4.106, and 13.944, respectively, the specificity of each index was higher than 90.00%, and the sensitivity was higher than 80.00% except PSV. Conclusion: Transvaginal ultrasound can not only accurately evaluate the ER of infertile women but also directly observe follicular development and monitor ovulation, which is of high value in evaluating ovarian reserve function and predicting ovulation.

Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/ß-catenin and MAPKs signaling pathways.

Although there are many therapeutic strategies such as surgery and chemotherapy, the prognosis of osteosarcoma (OS) is still far from being satisfactory. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. In the present study, we investigated the anti-OS activity of Alantolactone (ALT), a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium, and probed the possible mechanism involved. We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells. Then, we validated that ALT reduced migration, decreased invasion possibly through reversing epithelial mesenchymal transition (EMT) process and suppressing Matrix metalloproteinases (MMPs). Moreover, we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro. In addition, we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo. Mechanistically, ALT inhibited the activity of Wnt/ß-catenin and p38, ERK1/2 and JNK Mitogen Activated Protein Kinases (MAPKs) signal pathway. Notably, the combination of ALT and Wnt/ß-catenin inhibitor, as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation, migration and invasion of OS cells. Collectively, our results validate the ALT may inhibit proliferation, metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/ß-Catenin and MAPKs signaling pathways.

Schisandrin B suppresses osteosarcoma lung metastasis in vivo by inhibiting the activation of the Wnt/ß­catenin and PI3K/Akt signaling pathways.

Osteosarcoma (OS) is the most common malignant bone tumor worldwide and is associated with a poor prognosis, often being accompanied by lung metastasis at an early stage. At present, there are several side­effects associated with the OS clinical treatment of OS, with the treatment effects often being unsatisfactory. Thus, there is an urgent need for the development of safe and effective novel drugs for the treatment of OS. Schisandrin B (Sch B) has been previously demonstrated to exhibit antitumor properties. The present study was focused on the effects of Sch B on OS cells (143B, MG63, Saos2 and U2OS) in vitro and in vivo, and also on its possible antitumor mechanisms. In cell experiments, it was revealed that Sch B inhibited OS cell proliferation, migration and invasion, and increased OS cell apoptosis. As regards its biosafety, no notable effects of Sch B on the vitality of normal cells were observed. Mechanistically, it was demonstrated that Sch B blocked OS cell proliferation in the G1 phase. Subsequently, by using established animal models, it was revealed that Sch B significantly inhibited OS growth and lung metastasis in vivo. In summary, the results of the present study revealed that Sch B inhibited OS cell proliferation, migration and invasion, and promoted apoptosis via the inhibition of the Wnt/ß­catenin and PI3K/Akt signaling pathways, without causing any noticeable toxic effects on healthy cells at the therapeutic concentrations used. These findings suggest that Sch B has potential for use as a novel agent for the clinical treatment of OS.