CT-based radiomics prediction of CXCL13 expression in ovarian cancer.

BACKGROUND: Ovarian cancer, the most common malignancy in the female reproductive system, and patients tend to be at middle and advanced clinical stages when diagnosed. Therefore, early detection and early diagnosis have important clinical significance for the treatment of ovarian cancer patients. CXCL13, a chemokine with the ligands CXCR3 and CXCR5, is involved in the tumor metastasis process. PURPOSE: This study aimed to predict mRNA expression of CXCL13 in ovarian cancer tissues noninvasively. METHODS: Medical imaging data and transcriptomic sequencing data of the 343 ovarian cancer patients were downloaded from the TCIA and TCGA databases, respectively. Seventy-six radiomics features were extracted from the CT data. Seven features were selected for model construction by using logistic regression. Accuracy, specificity, sensitivity, positive predictive value, and negative predictive value were used to evaluate the radiomics model. RESULTS: High CXCL13 expression was found to be a significant protective factor for OS [HR (95% CI) = 0.755 (0.622-0.916), p = 0.004]. There was a significant positive correlation between CXCL13 and the degree of eosinophil infiltration. A calibration curve and the Hosmer-Lemeshow goodness-of-fit test showed that the prediction probability of the radiomics prediction model for high expression of CXCL13 was consistent with the true value. The AUC value of the nomogram model's ability to predict OS (12 months) was 0.758. The calibration plot and DCA both showed high clinical applicability for the nomogram model. CONCLUSION: CXCL13 is a candidate predictive biomarker for OC and correlates with the degree of plasma cell and eosinophil infiltration.

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic.

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in ß-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD.

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications.

Ezrin, a plasma membrane-microfilament linker, is a cytoskeletal organizer involved in many cellular activities by binding to the membrane protein-ezrin-cytoskeletal protein complex and regulating downstream signal transduction. Increasing evidence demonstrates that ezrin plays an important role in regulating cell polarity, proliferation and invasion. In this study, we analyzed the effects of ezrin on oocytes, follicle development, embryo development and embryo implantation. We reviewed the recent studies on the modalities of ezrin regulation and its involvement in the biological processes of female reproductive physiology and summarized the current research advances in ezrin inhibitors. These studies will provide new strategies and insights for the treatment of diseases.

Neogenin suppresses tumor progression and metastasis via inhibiting Merlin/YAP signaling.

From in situ growth to invasive dissemination is the most lethal attribute of various tumor types. This transition is majorly mediated by the dynamic interplay between two cancer hallmarks, EMT and cell cycle. In this study, we applied nonlinear association analysis in 33 cancer types and found that most signaling receptors simultaneously associating with EMT and cell cycle are potential tumor suppressors. Here we find that a top co-associated receptor, Neogenin (NEO1), inhibits colorectal cancer (CRC) and Glioma in situ growth and metastasis by forming a complex with Merlin (NF2), and subsequent simultaneous promoting the phosphorylation of YAP. Furthermore, Neogenin protein level is associated with good prognosis and correlates with Merlin status in CRC and Glioma. Collectively, our results define Neogenin as a tumor suppressor in CRC and Glioma that acts by restricting oncogenic signaling by the Merlin-YAP pathway, and suggest Neogenin as a candidate therapeutic agent for CRC and Glioma.

The effect of antidepressant therapy on a patient with progressive supranuclear palsy accompanied by depression, anxiety and fluctuating dementia.

Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease which can only be definitively confirmed at autopsy. It belongs to a family of conditions exhibiting Parkinson's syndrome, including Lewy body dementia (LBD) or dementia with Lewy body (DLB), and Parkinson's disease dementia (PDD). In regards to clinical manifestations, these two dementias have many overlapping characteristics. The declines of cognition in older patients of dementia are generally accompanied by depression, anxiety, hallucinations, delusions, eating and sleep disorders. This can lead to the difficulty in distinguishing the types of dementia and accurately diagnosing the disease. Herein, we present a complex case of PSP with depression, anxiety, and fluctuating dementia in which DLB was initially suspected. Before antidepressant therapy, the patient showed extrapyramidal symptoms as well as major depression, which lead to greatly impaired movement. Moreover, this patient was an older person with depression disorders, implicating further complexities of late life depression. After two weeks of therapy with antidepressants, the patient had reduced depressive symptoms, and even the somatic symptoms were improved. This case demonstrated that antidepressant therapy can be effective in improving emotion and cognition among patients with late life depression.

Global Research Trends on Infertility and Psychology From the Past Two Decades: A Bibliometric and Visualized Study.

Objectives: The aim of this study was to evaluate the global scientific output of research on infertility and psychology; explore the current status and trends in this field through the cooperation of authors, countries, and institutions; shed light on the direction of clinical infertility research in the future, and provide inspiration for targeted diagnosis and treatment of infertility. Methods: Research publications on infertility and psychology from the past two decades were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analyses were performed using VOSviewer software and the bibliometrix R package. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. Results: A total of 151 articles related to the study of infertility and psychology were identified. We observed a gradual increase in the number of publications from 2001 to 2021, and the trend has been relatively stable in the past eight years. Human Reproduction (England), as the leading journal publishing the most papers (29 articles), was cited in the most journals (1208 times). Boivin J was the most prolific author (16 articles), with the largest number of citations (890 times) and the highest h-index (14) during the past decades. Boivin J was also the leader with the highest publication frequency and more active cooperation with other top authors. The United Kingdom (34 papers) and Cardiff University (25 articles) contributed the most publications and were the leading contributors in this field. Active cooperation between countries and between institutions was observed, and analyses of articles and references were also shown. The main hot topics included matters related to women (39 times), in-vitro salt (31 times), infertility (30 times), couples (25 times), and impact (24 times). Conclusion: Our study results provide a comprehensive overview of the development of scientific literature, allowing relevant authors and research teams to recognize the current research status in this field. At the same time, infertility and psychology may soon become hotspots and should be closely monitored.

Comparison of a Small Dose of Oxycodone and Sufentanil for the Prevention of Sufentanil-Induced Cough during General Anesthesia Induction: A Prospective Randomized Controlled Trial.

Background: Sufentanil is widely used during anesthesia induction. However, it can cause coughing via different mechanisms. This study is aimed at evaluating the effectiveness of a small dose of oxycodone and sufentanil in suppressing sufentanil-induced cough (SIC) during general anesthesia induction. Methods: Of the 174 patients scheduled for elective surgery, 144 were eligible and randomly divided into 3 groups (n = 48). Five minutes before sufentanil bolus (0.4 µg/kg), patients in group O received 0.02  mg/kg oxycodone intravenously within 5 s, those in group S received 0.02 µg/kg sufentanil within 5 s, and those in group N received an equal volume of 0.9% normal saline within 5 s. Sufentanil was diluted to 5 µg/ml and administered within 5  s after pretreatment. The incidence and severity of cough in the three groups were evaluated within 1 minute after sufentanil injection during the anesthesia induction. Their mean arterial pressure (MAP) and heart rate (HR) were recorded at T0 (after entering the operation), T1 (3 minutes after pretreatment), T2 (before intubation), and T3 (1 minute after intubation). Results: The incidences of cough in group N, group O, and group S were 20 (41.6%), 7 (14.5%), and 6 (12.5%), respectively. Compared with group N, patients from group O and group S exhibited significantly reduced incidence and severity of cough, and the severity of cough in group O and group S was significantly reduced compared with group N (P < 0.05). No significant differences in the rangeability of MAP and HR were noted at the four time points in the three groups (P > 0.05). Conclusion. Preconditioning using intravenous oxycodone (0.02 mg/kg) or sufentanil (0.02 µg/kg) could represent an effective approach to reducing SIC in anesthesia induction and was associated with relatively stable hemodynamic state during general anesthesia. This trial is registered at Chinese Clinical Trial Registry with registration number ChiCTR1900021087.

Phenols and terpenoids: natural products as inhibitors of NLRP3 inflammasome in cardiovascular diseases.

Inflammatory infiltration has been implicated in the pathogenesis of cardiovascular diseases (CVDs). The NLRP3 inflammasome is involved in the development of several types of CVDs, including myocardial infarction, myocardial ischemia-reperfusion damage, heart failure, atrial fibrillation, and hypertension. Inhibiting the activity of NLRP3 inflammasome can inhibit the progress of CVDs. However, there is no NLRP3 inflammasome inhibitor in clinic, and it is very important to find a safe and effective NLRP3 inhibitor. Phenols and terpenoids are naturally natural products that have many anti-inflammatory effects in CVDs by modulating the NLRP3 inflammatory pathway. Thus, 20 natural products from phenols and terpenoids for the treatment of cardiovascular disease based on the inhibition of NLRP3 inflammasome were summarized and screened. Docking results showed salvianolic acid B and ellagic acid in phenols, and oridonin and triptolide in terpenoids had a better binding activity with NLRP3, which can provide theoretical support for finding novel NLRP3 inflammasome inhibitors or lead compounds in the future.

An innovative experimental apparatus for the analysis of sand production during natural gas hydrate exploitation.

Natural gas hydrate (NGH) will become a significant potential energy source in the post-oil era due to its large reserves, wide distribution, high energy density, and low pollution. Sand production is one of the main problems that cause the impossible long-term production of NGH. This paper presents an experimental apparatus that was developed to synthesize NGH and hydrate-bearing sediments and was applied to analyze the sand production and sand control mechanism during hydrate exploitation. The sand production and sand control tests of NGH can be conducted over a temperature range varying from 253.15 to 323.15 K and the maximum chamber pressure and overlying pressure up to 30 MPa. This apparatus is mainly composed of the simulated sand production system, the temperature and pressure control system, and the measurement control system. The simulated sand production system consists of a movable overlying pressure loader, a strain sensor, a simulated reservoir chamber, a sand control system, and a sand production monitoring system. A visual gas-liquid-solid separation tank is applied to observe the gas, water, and sand production. The basic principles of this apparatus are discussed, and a series of experiments were performed to verify that sand production and sand control can be practically applied in the exploitation of NGH reservoirs.

A Novel Drug Delivery System: the Encapsulation of Naringenin in Metal-Organic Frameworks into Liposomes.

Poorly water-soluble naringenin (NAR) was selected as a model drug and loaded into the porous MOFs for the construction of NAR@ZIF-8 inclusion complex. By film dispersion method, NAR@ZIF-8 was further encapsulated into liposomes to fabricate a novel drug delivery system. Liposomes and a novel drug delivery system were established. Subsequently, the lipid-drug ratio, phospholipid-cholesterol ratio, and hydration temperature were investigated using the Box-Behnken design based the single factor experiment. The prepared liposomes system showed spherical or quasi-spherical shape, uniform particle size distribution, and complete structure. More specifically, the average particle size was 113.2 ± 1.4 nm, and zeta potential was - 7.536 ± 0.264 mV. Moreover, the drug release behaviors of NAR, NAR@ZIF-8, and NAR@ZIF-8 liposomes were explored in vitro. Compared with free NAR and NAR@ZIF-8 which exhibited a burst drug release, NAR@ZIF-8 liposomes showed a more sustained release behavior with 79.86% drug release in 72 h. In vitro cytotoxicity experiments showed that, compared with free NAR and NAR@ZIF-8, NAR@ZIF-8 liposomes exhibited higher inhibition efficiency on lung adenocarcinoma A549 cells and gastric cancer SGC-7901 cells in a concentration-dependent manner.

Phytochemicals as potential IKK-ß inhibitor for the treatment of cardiovascular diseases in plant preservation: terpenoids, alkaloids, and quinones.

Modulation of inhibitor kappa B kinase-beta (IKK-ß) kinase activity could be useful for preventing inflammation that serves an efficient role in protection against cardiovascular diseases (CVDs). IKK-ß induces inflammation by activating transcription factor NF-kappa B (NF-κB) through phosphorylation of IκB. Therefore, IKK-ß is considered an interesting target for protecting and treating CVDs. The cardioprotective potential of terpenoids, alkaloids and quinines may be related to modulating inflammatory responses. In this study, the interactions between different classes of inhibitors and IKK-ß were investigated, through the application of SystemsDock. Molecular docking results showed that Diosgenin and Ginsenoside Re were the top docking score compounds. Diosgenin and Ginsenoside Re are the most promising IKK-ß inhibitors in terpenoids, alkaloids, and quinones. Diosgenin and Ginsenoside Re could be helpful to find the lead compounds on designing and developing novel cardioprotective agents.

Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone.

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5-3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.

Ferromagnetic properties in low-doped zigzag graphene nanoribbons.

The temperature-dependent edge magnetic susceptibility [Formula: see text] and the uniform magnetic susceptibility χ in zigzag graphene nanoribbons is studied within the Hubbard model on a honeycomb lattice. By using the determinant quantum Monte Carlo (DQMC) method, it is found that the ferromagnetic fluctuations at the zigzag edge dominate around half-filling, and that the fluctuations are strengthened markedly by the on-site Coulomb interaction U, which may lead to a possible high-temperature edge ferromagnetic behaviour in low-doped zigzag graphene nanoribbons.

[Clinical research of lung resection surgery with microinjection acupuncture and drug anesthesia instead of traditional acupuncture anesthesia].

OBJECTIVE: To explore the feasibility and safety on lung resection surgery with the combined method of microinjection acupuncture (MIA) and intravenous anesthesia instead of compound traditional acupuncture and drug anesthesia (ADA). METHODS: Ninety cases of lung resection surgery were randomized into a general anesthesia group, a MIA group and a ADA group, 30 cases in each one. In the general anesthesia group, before surgery, the intramuscular injection of atropine 0. 5 mg was used; during surgery, the anesthesia induction was followed with intravenous injection of fentanyl citrate, propofol and rocuronium bromide and the dosage was increased accordingly; after surgery, the analgesia pump was applied. In the MIA group, on the basis of general anesthesia, before anesthesia induction, the acupoint catgut embedding was applied to Jiaji (EX-B 2) of T4 , T6 and T, , Feishui (BL 13), Xinshu (BL 15) and Geshu (BL 17) on the affected side and bilateral Quchi (LI 11) and Zusanli (ST 36); after surgery, the analgesia pump was applied. In the ADA group, on the basis of general anesthesia, before! anesthesia induction, electroacupuncture (EA) was applied to Hegu (LI 4), Neiguan (PC 6) , Houxi (SI 3) and Zhigou (TE 6) for 30 min; during surgery, EA and intravenous medication were combined at the same acupoints as those before surgery; after surgery, moxibustion and the analgesia pump were applied in combination for analgesia. In each group, the biological indices were monitored during surgery at 11 time points named T. (before anesthesia I induction), T1 (intubation in general anesthesia induction), T2 (skin incision), T3 (rib exposure in muscular incision) T. (chest open), T, (lung removal), T6 (drainage tube implantation), T7 (chest closure), T (muscular stitching), T, (skin stitching) and T0 (extubation). The actual dosage of anesthetics during surgery and the, dosage of fentanyl citrate in analgesia pump were quantified after surgery. Results (1) In the MIA group and ADA group, the increased dosage of fentanyl citrate was less than that in the general anesthesia group [(1. 23±0. 28) µg . kg-1 . h-1 vs (2. 4±0. 54µg. kg-1 . h-1, (1. 1±0. 38µg . kg-1 . h-1 vs (2. 4±0. 54µg. kg-1 . h-1 , both P<0. 05]. The increased dosage of propofol and rocuronium bromide was not different during surgery among the groups (all P>0. 05). (2) In the MIA group and ADA group, after surgery, the increased dosage of fentanyl citrate was less than that in the general anesthesia group [(11. 0±1. 04)µg/kg vs (15. 4±1. 52µg/kg, (11. 5±1. 38µg/kg vs (15. 4±1. 52µg/kg, both P<0. 05], reducing by 25% in comparison. (3) The differences in heart rate and blood pressure at 11 time points during surgery were not significant among the three groups (all P>0. 05). CONCLUSION: n The combined method of MIA and intravenous anesthesia significantly reduces the dosage of intravenous anesthetics during and after lung resection surgery as compared with ADA, presenting the similar analgesic effect as simple intravenous medication and the good safety. The combined method of MIA and intravenous anesthesia is much

Fluorine-18 labeling by click chemistry: multiple probes in one pot.

Click chemistry has been widely applied in drug development including radiopharmaceuticals and has shown great advantages. Here we reported a novel strategy for rapid preparation of multiple (18)F labeled PET probes in one pot using the 'Click Reaction' of Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of terminal alkynes and organic azides (CuAAC). Preliminary results showed its high efficiency and potential for speeding up the preclinical screening of PET probes.

Radiolabeling of RGD peptide and preliminary biological evaluation in mice bearing U87MG tumors.

2-[(18)F]Fluoroethyl azide ([(18)F]FEA) and terminal alkynyl modified propioloyl RGDfK were selected in this study. [(18)F]FEA was prepared by nucleophilic radiofluorination of 2-azidoethyl 4-toluenesulfonate with radiochemical yield of 71 ± 4% (n = 5, decay-corrected). We assessed the various conditions of the CuAAC reaction between [(18)F]FEA and propioloyl RGDfK, which included peptide concentration, reaction time, temperature and catalyst dosage. The (18)F-labeled-RGD peptide ([(18)F]F-RGDfK) could be obtained in 60 min by a two-step radiochemical synthesis route, with total radiochemical yield of 60 ± 2% (n = 3, decay-corrected) through click chemistry. [(18)F]F-RGDfK showed high stability in phosphate buffered saline and new-born calf serum. Micro-PET imaging at 1 h post injection of [(18)F]F-RGDfK showed medium concentration of radioactivity in tumors while much decreased concentration in tumors in the blocking group. These results showed that [(18)F]F-RGDfK obtained by click chemistry maintained the affinity and specificity of the RGDfK peptide to integrin α(v)ß(3). This study provided useful information for peptide radiofluorination by using click chemistry.

Preliminary biological evaluation of ¹²5I-labeled anti-carbonic anhydrase IX monoclonal antibody in the mice bearing HT-29 tumors.

OBJECTIVE: To evaluate ¹²5I-labeled anti-carbonic anhydrase IX monoclonal antibody (¹²5I-MAb) as a novel single-photon emission computed tomography tracer for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. METHODS: Anti-carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the iodogen method. The radiochemical purity of ¹²5I-MAb was measured by radio-thin-layer chromatography. The in-vitro stability of ¹²5I-MAb was determined in PBS (0.05 mol/l, pH 7.4) or new-born calf serum at 37°C, and analyzed by radio-thin-layer chromatography. A biodistribution study and planar imaging were carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29 tumors was analyzed by immunohistochemistry. RESULTS: ¹²5I-MAb was obtained with a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born calf serum. Furthermore, the biodistribution study showed specific tumor uptake in the mice bearing HT-29 tumors, and planar imaging with ¹²5I-MAb 48 h post injection showed a high concentration of radioactivity in tumors and a much decreased concentration in tumors in the blocking group. An immunohistochemical analysis showed the expression of CA IX in HT-29 tumors. CONCLUSION: The preliminary biodistribution study and results from planar imaging showed the potential of ¹²5I-MAb as an agent for tumor diagnosis and encouraged further investigation.