RACGAP1 knockdown synergizes and enhances the effects of chemotherapeutics on ovarian cancer.

Among the three most prevalent cancers affecting the female reproductive system, ovarian cancer (OV) ranks as the second most frequently diagnosed. It is important to investigate the genomic complexity of OV to develop diagnostic and therapeutic strategies. Through the utilization of bioinformatics analysis, it was determined that RacGTPase Activating Protein 1 (RACGAP1) holds significant significance in the field of OV chemotherapeutics, an aspect that has not been thoroughly explored in prior investigations. In our study, a notable increase in RACGAP1 expression was detected in ovarian cancer, demonstrating a robust association with clinicopathological features and patient prognosis. In vivo and in vitro testing revealed that RACGAP1 acts synergistically with chemotherapeutics to enhance their effects on ovarian cancer. Furthermore, an interaction between RACGAP1 and the subunit G2 of the condensin II complex, known as non-SMC condensin II complex subunit G2 (NCAPG2), has been identified. Our findings may provide new insight for improving therapeutic strategies for OV.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

A Social Media-Based Mindfulness Psycho-Behavioral Intervention (MCARE) for Patients With Acute Coronary Syndrome: Randomized Controlled Trial.

BACKGROUND: Psychological distress is common among patients with acute coronary syndrome (ACS) and has considerable adverse impacts on disease progression and health outcomes. Mindfulness-based intervention is a promising complementary approach to address patients' psychological needs and promote holistic well-being. OBJECTIVE: This study aims to examine the effects of a social media-based mindfulness psycho-behavioral intervention (MCARE) on psychological distress, psychological stress, health-related quality of life (HRQoL), and cardiovascular risk factors among patients with ACS. METHODS: This study was a 2-arm, parallel-group randomized controlled trial. We recruited 178 patients (mean age 58.7, SD 8.9 years; 122/178, 68.5% male) with ACS at 2 tertiary hospitals in Jinan, China. Participants were randomly assigned to the MCARE group (n=89) or control group (n=89). The 6-week intervention consisted of 1 face-to-face session (phase I) and 5 weekly WeChat (Tencent Holdings Ltd)-delivered sessions (phase II) on mindfulness training and health education and lifestyle modification. The primary outcomes were depression and anxiety. Secondary outcomes included psychological stress, HRQoL, and cardiovascular risk factors (ie, smoking status, physical activity, dietary behavior, BMI, blood pressure, blood lipids, and blood glucose). Outcomes were measured at baseline (T0), immediately after the intervention (T1), and 12 weeks after the commencement of the intervention (T2). RESULTS: The MCARE group showed significantly greater reductions in depression (T1: ß=-2.016, 95% CI -2.584 to -1.449, Cohen d=-1.28, P<.001; T2: ß=-2.089, 95% CI -2.777 to -1.402, Cohen d=-1.12, P<.001) and anxiety (T1: ß=-1.024, 95% CI -1.551 to -0.497, Cohen d=-0.83, P<.001; T2: ß=-0.932, 95% CI -1.519 to -0.346, Cohen d=-0.70, P=.002). Significantly greater improvements were also observed in psychological stress (ß=-1.186, 95% CI -1.678 to -0.694, Cohen d=-1.41, P<.001), physical HRQoL (ß=0.088, 95% CI 0.008-0.167, Cohen d=0.72, P=.03), emotional HRQoL (ß=0.294, 95% CI 0.169-0.419, Cohen d=0.81, P<.001), and general HRQoL (ß=0.147, 95% CI 0.070-0.224, Cohen d=1.07) at T1, as well as dietary behavior (ß=0.069, 95% CI 0.003-0.136, Cohen d=0.75, P=.04), physical activity level (ß=177.542, 95% CI -39.073 to 316.011, Cohen d=0.51, P=.01), and systolic blood pressure (ß=-3.326, 95% CI -5.928 to -0.725, Cohen d=-1.32, P=.01) at T2. The overall completion rate of the intervention (completing ≥5 sessions) was 76% (68/89). Positive responses to the questions of the acceptability questionnaire ranged from 93% (76/82) to 100% (82/82). CONCLUSIONS: The MCARE program generated favorable effects on psychological distress, psychological stress, HRQoL, and several aspects of cardiovascular risk factors in patients with ACS. This study provides clues for guiding clinical practice in the recognition and management of psychological distress and integrating the intervention into routine rehabilitation practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033526; https://www.chictr.org.cn/showprojEN.html?proj=54693.

Nurse-to-patient ratios and readiness for hospital discharge: A moderated mediation model.

AIM: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model. DESIGN: A cross-sectional study was carried out from March 2021 to December 2022. METHODS: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist. RESULTS: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.

Clinical significance of episcleral venous fluid wave in gonioscopy-assisted transluminal trabeculotomy.

AIM: To evaluate the clinical significance of checking episcleral venous fluid wave (EVFW) during gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open angle glaucoma (OAG). METHODS: This retrospective case series study comprised 30 patients (45 eyes) with OAG underwent GATT. The location and extent of EVFW were examined and graded after intraoperative compression flushing of the anterior chamber angle during the operation. Patients were followed up for 1y. A complete success for surgery is defined as a postoperative intraocular pressure (IOP) <18 mm Hg without any anti-glaucoma medication. IOP<18 mm Hg with less than two anti-glaucoma medications is defined as qualified success, while the control of IOP requiring three anti-glaucoma medications is considered as unsuccess. RESULTS: The mean IOP was 35.38±7.16 mm Hg before surgery and 15.52±4.22 mm Hg 1y after surgery (P<0.01). The average number of anti-glaucoma medication was 2.8±1.2 (2-4) preoperation and 0.6±1.3 (0-3) 1y postoperation (P<0.01). The success rate of the operation was 93.33%. Complete success rate was 66.67%, qualified success rate was 26.67%, and 6.66% of unsuccessful cases required reoperation. EVFW of all cases was grade 2-4, and the percentages of grade 2, 3 and 4 were 33.33%, 40.0% and 26.67%, respectively. The distribution and percentage of EVFW were inferior (36%), nasal (28%), superior (20%), and temporal (16%). The EVFW grade of complete success patients was 3.4±0.6 (3-4), and that of qualified success patients was 2.6±1.0 (2-4). The larger the range of EVFW, the lower the IOP, and the better the IOP reduction effect. CONCLUSION: During GATT surgery, pressurized irrigation of anterior chamber to check EVFW can reduce the outflow resistance of aqueous humor and increase the effect of postoperative IOP. The range of EVFW is negatively correlated with postoperative IOP. Therefore, EVFW may be a valuable prognostic indicator for the success of GATT surgery.

Shikonin prevents mice from heat stroke-induced death via suppressing a trigger IL-17A on the inflammatory and oxidative pathways.

Heat stroke (HS) is the deadliest disease. Due to the complex pathogenesis of HS, lack of effective therapeutic drugs for clinical treatment. Shikonin (SK) is the main active compound of Radix Arnebiae, which was evaluated on the HS model (temperature: (41 ± 0.5) ℃, relative humidity: (60 ± 5) %) via pathological and biochemical approaches in vivo and in vitro. Upon the dose of 10 mg.kg-1, SK delays the rising rate of core temperature, prolongs the survival time of mice, and improves organ injury and coagulation function markedly. Serum HS biomarkers interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were decreased significantly by SK, which contribute to liver and lung protection in the models. Three pathways' responses to heat-stress were found to have a close connection with the IL-17 pathway via RNA sequencing and network analysis. WB and IHC results showed that the nuclear factor-κB (NF-κB) p65 in the SK group was down-regulated (P < 0.05). The expressions of nuclear factor erythroid 2 like 2 (NFE2L2/Nrf2) and heat shock protein 70 (HSP70) were up-regulated (P < 0.05). Additional administration of recombinant IL-17A protein on the HS model up-regulated the expression level of NF- κB p65 in the liver and lung tissue, additional intraperitoneal injection of IL-17A antibody in mice has a synergistic effect with SK in inhibiting tissue inflammatory response and protecting HS. In summary, SK was proved an effective compound for fulfilling the anti-inflammatory and antioxidative capacity of the HS model by reducing the production and inhibiting the expression of IL-17A.

Semaphorin 3A inhibits tumor progression via the downregulation of Lin28B in ovarian cancer.

Semaphorin 3A (Sema3A) has recently been proven to play an essential role in tumorigenesis. Here, the role of Sema3A in ovarian cancer is explored. The prognostic value of Sema3A was evaluated using the Kaplan-Meier plotter database, and stable expression cells were established by the delivery of lentivirus harboring SEMA3A cDNA or shRNA into OVCA433 and SKOV3 cells, respectively. Then CCK-8 assay, colony-formation assay, wound-healing assay, and Transwell assay were utilized to verify the effect of Sema3A on tumorigenesis. Co-cultures of ovarian cancer cells (OVCA433 and SKOV3) with a conditional medium collected from the established cells were further utilized to confirm the function of Sema3A. Then, the RNA-seq assay was adopted to explore the underlying mechanism. The results demonstrated that low expression of Sema3A was predictive of poor overall survival in patients with ovarian cancer. Functional experiments revealed that Sema3A inhibited proliferation, migration, and invasion in ovarian cancer cells. Secreted Sema3A in a conditioned culture medium also exhibited an anti-tumor effect in ovarian cancer cells. RNA-seq assay suggested that focal adhesion and Lin28B were involved in regulating Sema3A. Rescue assays further verified that Lin28B/ROCK1 axis was vital in the regulation of Sema3A and Lin28B significantly upregulated ROCK1 through let-7g microRNA. The presented data indicate that Sema3A inhibits proliferation and metastasis via the downregulation of Lin28B/ROCK1 in ovarian cancer.

eHealth Literacy of Chinese Residents During the Coronavirus Disease 2019 Pandemic: A Cross-sectional Survey.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a leading societal concern. eHealth literacy is important in the prevention and control of this pandemic. The purpose of this study is to identify eHealth literacy of Chinese residents about the COVID-19 pandemic and factors influencing eHealth literacy. A total of 15 694 individuals clicked on the link to the questionnaire, and 15 000 agreed to participate and completed the questionnaire for a response rate of 95.58%. Descriptive statistics, χ 2 test, and logistic regression analysis were conducted to analyze participants' level of eHealth literacy about COVID-19 and its influencing factors. The results showed 52.2% of participants had relatively lower eHealth literacy regarding COVID-19 (eHealth literacy score ≤ 48). The scores of the information judgment dimension (3.09 ± 0.71) and information utilization dimension (3.18 ± 0.67) of the eHealth literacy scale were relatively lower. The logistics regression showed that sex, age, education level, level of uncertainty, having people around the respondent diagnosed with COVID-19, relationship with family, and relationship with others were associated to eHealth literacy (χ 2 = 969.135, P < .001). The public's eHealth literacy about COVID-19 needs to be improved, especially the ability to judge and utilize online information. Close collaboration among global health agencies, governments, healthcare institutions, and media is needed to provide reliable online information to the public. Interventions to improve eHealth literacy should take into account and accentuate the importance of sex, age, educational background, level of uncertainty, exposure to disease, and social support.

The combined analgesic, sedative, and anti-gastric cancer mechanisms of Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo based on integrated ethnopharmacological data.

ETHNOPHARMACOLOGY RELEVANCE: As a Yi medicine for eliminating wind to relieve pain, Tinospora sagittata var. yunnanensis (S. Y. Hu) H. S. Lo (TSY) is widely used to treat sore throat, stomach pain, bone and muscle injuries, and tumors; however, the material basis and mechanism of action remain unclear. AIM OF THE STUDY: This study aims to investigate the potential active compounds of TSY and related pharmacological mechanisms against gastric cancer using a multitarget strategy. MATERIALS AND METHODS: The main chemical components of TSY were collected through a literature review and database searches. The components were further screened for ADMET properties, and their targets were predicted using network pharmacology (admetSAR) and substructure-drug-target network-based inference (SDTNBI) approaches in silico. The pharmacological mechanism of action of TSY extract for pain relief, sedation, and anti-gastric cancer activities were identified via in vivo and in vitro biochemical analyses. RESULTS: Here, 28 chemical components were identified, 7 active compounds were selected, and 75 targets of TSY extract were predicted. A compound-target-disease network topological approach revealed that the predicted targets are highly related to the digestive system and nervous system. Network pharmacology results suggested that the anti-gastric cancer activity of TSY was highly correlated with its analgesic and sedative targets and MAPK. In vivo experiments confirmed that TSY extract not only reduced the number of voluntary activities in the mouse model but also exhibited a synergistic effect on sodium pentobarbital-induced sleep, reduced the number of mice exhibiting writhing responses to acetic acid, and increased the hot plate pain threshold of mice. Thus, TSY extract exhibits good analgesic and sedative effects. The TSY extract inhibited HGC-27 cell proliferation and induced apoptosis by regulating apoptotic proteins (BAX, BCL-2 and BCL-XL) in vitro. CONCLUSIONS: TSY exhibits combined analgesic, sedative, and anti-gastric cancer activities.

Laparoscopic single-layer running "trapezoid-shaped" suture versus mechanical stapling for esophagojejunostomy after total gastrectomy for gastric cancer: cost-effect analysis of propensity score-matched study cohorts.

OBJECTIVES: Totally laparoscopic total gastrectomy has been developed with difficulty in intracorporeal esophagojejunostomy. Although mechanical stapling has been widely used for intracorporeal esophagojejunostomy, manual suture holds great promise with the emergence of high-resolution 3D vision and robotic surgery. After exploration of how to improve the safety and efficiency of intracorporeal suture for esophagojejunostomy, we recommended the technique of single-layer running "trapezoid-shaped" suture. The cost-effectiveness was analyzed by comparing with conventional mechanical stapling. METHODS: The study retrospectively reviewed the patients undergoing laparoscopic gastrectomy for gastric cancer from January 2010 to December 2021. The patients were divided into two cohorts based on the methods of intracorporeal esophagojejunostomy: manual suture versus stapling suture. Propensity score matching was performed to match patients from the two cohorts at a ratio of 1:1. Then group comparison was made to determine whether manual suture was non-inferior to stapling suture in terms of operation time, anastomotic complications, postoperative hospital stay, and surgical cost. RESULTS: The study included 582 patients with laparoscopic total gastrectomy. The manual and stapling suture for esophagojejunostomy were performed in 50 and 532 patients, respectively. In manual suture cohort, the median time for the whole operation and digestive tract reconstruction were 300 min and 110 min. There was no anastomotic bleeding and stenosis but two cases of anastomotic leak which occurred at 3 days after surgery. The median length of postoperative hospital stay was 11 days. After propensity score matching, group comparison yielded two variables with statistical significance: time for digestive tract reconstruction and surgery cost. The manual suture cohort spent less money but more time for esophagojejunostomy. Intriguingly, the learning curve of manual suture revealed that the time for digestive tract reconstruction was declined with accumulated number of operations. CONCLUSIONS: Laparoscopic single-layer running "trapezoid-shaped" suture appears safe and cost-effective for intracorporeal esophagojejunostomy after total gastrectomy. Although the concern remains about prolonged operation time for beginners of performing the suture method, adequate practice is expected to shorten the operation time based on our learning curve analysis.

Serum calcium, albumin, globulin and matrix metalloproteinase-9 levels in acute cerebral infarction patients.

BACKGROUND: Hemorrhagic transformation (HT) is a common complication in patients with cerebral infarction. However, its pathogenesis is poorly understood. The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy. AIM: To investigate the predictive value of serum calcium, albumin, globulin and matrix metalloproteinase-9 (MMP-9) levels for HT after intravenous thrombolysis (IVT) in patients with acute cerebral infarction. METHODS: Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects. They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis. Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group. Serum calcium, albumin, globulin and MMP-9 levels were compared between the two groups. Regression analysis was used to discuss the relationship between these indices and HT. RESULTS: The previous history of hypertension, diabetes, atrial fibrillation, cerebrovascular diseases, smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction (all P > 0.05). The National Institutes of Health stroke scale (NHISS) score was associated with HT after IVT in patients with acute cerebral infarction (P < 0.05). The serum calcium and albumin levels were lower in the observation group than in the control group (all P < 0.05). The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group (all P < 0.05). Logistic regression analysis showed that NHISS score, serum calcium, albumin, globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction (P < 0.05). CONCLUSION: Serum calcium, albumin, globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction. Moreover, NHISS score can be used as a predictor of post-thrombolytic HT.

The critical role of glutathione redox homeostasis towards oxidation in ermanin-induced melanogenesis.

Vitiligo is a depigmented disease featured as diagnosis simplicity and cure difficulty. Its occurrence and development are associated with a variety of factors, including oxidative stress, heredity and immunity, etc. Existing drugs for the treatment of vitiligo are to reduce the death of melanocytes and induce pigment accumulation as the main treatment strategy. Ermanin, a member of the flavonoids, is extracted from bee glue which is wildly used to treat vitiligo in traditional Chinese medicine. Therefore, this article discusses the relationship between melanogenesis and glutathione redox homeostasis by ermanin via biochemical and free radical approaches in vivo and in vitro. In this study, we found that ermanin effectively increased the melanin content at the in vivo model (zebrafish). Moreover, the melanin levels at the in vitro models (B16F10 cells and primary melanocytes) were also increased significantly accompanied with a shift of glutathione redox homeostasis towards oxidation. Ermanin also significantly enhanced the activity of tyrosinase. Meanwhile, ermanin increased the expression levels of TYR, TRP-1, and DCT genes, while ROS accumulation and glutathione depletion mediated the accumulation of pigments caused by ermanin, which increased the production of pigments and regulated the expression mRNA levels of TYR and DCT genes. From the perspective of pigment production regulation pathways, western blot showed that the pigment accumulation caused by ermanin was closely related to the CREB-MITF pathways, it activated CREB, TYR, TRP-1, and DCT proteins. The use of CREB specific inhibitor 666-15 and MITF inhibitor ML329 confirmed that the pigment accumulation caused by ermanin was positively correlated with CREB and MITF proteins. Our findings revealed the potential mechanisms by which ermanin promoted the production of melanin through activated CREB-MITF signaling pathway and glutathione redox homeostasis towards oxidation function as a signal are beneficial to melanin production and will help develop novel therapeutic approaches for vitiligo.

Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aß1-42 aggregation effectively ranged from 45.9-94.5 % at 20 µM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 µM, and it could disassemble the self-induced Aß1-42 aggregation fibrils with ratio of 57.1 % at 20 µM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aß aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aß1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

Hematopoietic Stem-Cell Transplantation versus Immunosuppressive Therapy in Patients with Adult Acquired Severe Aplastic Anemia: A Cost-Effectiveness Analysis.

OBJECTIVE: Controversy remains regarding which therapy to initially select for severe aplastic anemia (SAA) patients aged 35-50. This cost-effectiveness analysis aimed to use the Markov model to compare immunosuppressive therapy (IST) with hematopoietic stem-cell transplantation (HSCT) in age-stratified patients with SAA. METHODS: A cost-effectiveness analysis using a Markov model compared IST with HSCT in age-stratified patients with SAA. Baseline data were derived from a systematic literature review and collected from Huashan Hospital, Fudan University. The primary outcome was an incremental cost-effectiveness ratio (ICER). RESULTS: The HSCT strategy dominated in patients aged 18-35 even though it was $146,970 more expensive than IST, and the ICER of HSCT to IST was $14,054.19/quality-adjusted life-year (QALY), which was less than the willingness-to-pay value of $25,397.57/QALY. The IST strategy dominated in patients aged 35-50, because it was $72,009 less expensive than HSCT and yielded 3.24 QALYs more than HSCT. The model was vigorous in the sensitivity analyses of the key variables tested through the plausible ranges that were acquired from costing sources and previously published literature. CONCLUSION: The preferred induction strategy for patients aged 18-35 with SAA appears to be HSCT, and the preferred strategy for patients aged 35-50 is IST, which minimizes costs while maximizing QALYs.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

Active ingredients targeting Nrf2 in the Mongolian medicine Qiwei Putao powder: Systematic pharmacological prediction and validation for chronic obstructive pulmonary disease treatment.

ETHNOPHARMACOLOGY RELEVANCE: Qiwei Putao powder (Uzhumu-7 in Mongolian) is a traditional Mongolian medicine, which has been widely used for alleviating cough and dyspnea, especially in aged individuals in both Inner Mongolia Autonomous Region and Xinjiang Uygur Autonomous Region of China. However, the active ingredients and exact pharmacological mechanism remain unclear. MATERIALS AND METHODS: The protective effect of Qiwei Putao powder (QPP) on mice with cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced chronic obstructive pulmonary disease (COPD) was assessed by histopathological hematoxylin and eosin staining, lung coefficient determination and measurement of cytokine levels. The bioactive ingredients and potential targets of the QPP were screened and detected with network pharmacology method and ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The mechanism and efficacy of active ingredients were further validated in COPD mice with immunohistochemistry tests, cytokine level measurement and RT-PCR. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in the nucleus, interleukin (IL)-1ß, superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) kits to evaluate oxidative stress and inflammatory conditions in vivo after treatment. The expression of Nrf2 and downstream genes was detected by RT-PCR. RESULTS: QPP can alleviate pathological changes in the lung during COPD progression. Sixty-one bioactive molecules were identified in QPP, 42 candidate compounds present in UPLC-Q/TOF-MS and 30 predicted COPD-related targets were generated by in silico analysis. A therapeutic network was constructed with all potential targets to predict the preventive effects of the targets on respiratory disease as well as cardiovascular diseases, nervous system diseases, musculoskeletal diseases and bacterial infections. Targets related to inflammation, immunity and oxidative stress (prostaglandin-endoperoxide synthase 2, PTGS2; Nrf2; heat shock protein 90 alpha class A1, HSP90AA1; nitric oxide synthase, NOS2A; etc.) influenced COPD progression the most. We found that Nrf2 promotes a cell antioxidant response and is a key common target in the response to treatment with isoliquiritigenin (ISL), pterostilbene (PTE) and quercetin (QUE), the highly absorbed active ingredients in the formula. The data showed a strong synergistic protective role of these three molecules against the death of human type II alveolar adenocarcinoma (A549) cells through Nrf2 activation following H2O2 exposure and provide pharmacological mechanism of QPP in COPD treatment.

Comparison of Three Screening Methods for Sarcopenia in Community-Dwelling Older Persons.

OBJECTIVE: The 2019 Asian Working Group on Sarcopenia in Older People (AWGS 2019) recommends using either calf circumference or the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) or SARC-F combined with calf circumference (SARC-CalF) questionnaires for sarcopenia screening. The aim of this study was to compare the ability and applicability of calf circumference, SARC-F, and SARC-CalF for screening sarcopenia among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 1050 community-dwelling older people were enrolled. METHODS: Sarcopenia was diagnosed according to the AWGS 2019 criteria: bioimpedance analysis for appendicular skeletal muscle index, hand grip, and 6-m gait speed test. Participants also completed the SARC-F questionnaire and calf circumference measurement. The screening tools' performances were evaluated through receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and sensitivity/specificity analyses. RESULTS: Sarcopenia was identified in 263 (25.0%) participants by the AWGS 2019 criteria. Calf circumference had a sensitivity of 81.4% and a specificity of 77.0%. Sensitivity and specificity of SARC-F for screening sarcopenia were 17.9% and 93.7%, respectively. SARC-CalF improved the sensitivity of SARC-F (47.5%) while keeping similar specificity (92.0%). The AUCs of calf circumference, SARC-F, and SARC-CalF were 0.79 [95% confidence interval (CI), 0.77-0.82], 0.56 (95% CI, 0.52-0.59), and 0.70 (95% CI, 0.67-0.73), respectively. The differences across ROC curves were statistically significant among 3 screening tools (P < .001). CONCLUSIONS AND IMPLICATIONS: The overall screening ability of calf circumference was better than that of SARC-F and SARC-CalF for sarcopenia in community-dwelling older persons despite gender, age, and cognitive function. SARC-F and SARC-CalF have high specificity but are susceptible to the preceding factors.

[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen].

OBJECTIVE: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML). METHODS: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared. RESULTS: The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups. CONCLUSION: Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.