Downregulation of HHLA2 inhibits ovarian cancer progression via the NF-κB signaling pathway and suppresses the expression of CA9.

HHLA2 has been recently demonstrated to play multifaceted roles in several types of cancers. However, its underlying mechanism in the progression of human ovarian cancer (OC) remains largely unexplored. In the present study, we aimed to determine whether downregulation of HHLA2 inhibited malignant phenotypes of human OC cells and explore its specific mechanism. Our results revealed that downregulation of HHLA2 by transfection with a lentiviral vector significantly suppressed the viability, invasion, and migration of OC cells. Interaction study showed that downregulation of HHLA2 in OC cells reduced the expression of CA9 and increased the expressions of p-IKKß and p-RelA. Conversely, the viability, invasion, and migration of HHLA2-depleted OC cells were increased when CA9 was upregulated. In vivo, we found that downregulation of HHLA2 significantly inhibited tumor growth, which was reversed by CA9 overexpression. In addition, downregulation of HHLA2 inhibited the OC progression via activating the NF-κB signaling pathway and decreasing the expression of CA9. Collectively, our data suggested a link between HHLA2 and NF-κB axis in the pathogenesis of OC, and these findings might provide valuable insights into the development of novel potential therapeutic targets for OC.

Ibrutinib versus bendamustine plus rituximab for first-line treatment of 65 or older patients with untreated chronic lymphocytic leukemia without del(17p)/TP53 mutation in China: a lifetime economic research study.

BACKGROUND: The incidence and mortality rates of patients with chronic lymphocytic leukemia (CLL) in China have recently increased. This study performed a long-term economic evaluation of the first-line treatment strategies ibrutinib (IB) or bendamustine (BE) plus rituximab (RI) for previously untreated older patients with CLL without the del(17p)/TP53 mutation in China. METHODS: Based on clinical data from large, randomized trials, a Markov model including four disease states (event-free survival, treatment failure, post-treatment failure, and death) was used to estimate the incremental costs per quality adjusted-life year (QALY) gained from the first-line IB strategy versus the BE plus RI strategy over a 10-year period. All costs were adjusted to 2022 values based on the Chinese Consumer Price Index, and all costs and health outcomes were discounted at an annual rate of 5%. Sensitivity analysis was performed to confirm the robustness of base-case results. RESULTS: Compared to the first-line BE plus RI strategy, first-line IB treatment achieved 1.17 additional QALYs, but was accompanied by $88,046.78 (estimated in 2022 US dollars) in decremental costs per patient over 10 years. Thus, first-line treatment with IB appeared to have absolute dominance compared to the BE plus RI strategy. Sensitivity analysis confirmed the robustness of these results. CONCLUSIONS: The first-line treatment with IB is absolutely cost-effective compared to the first-line BE plus RI treatment strategy for 65 or older patients with CLL without the del (17p)/TP53 mutation from the Chinese payer perspective. Therefore, it is strongly recommended that Chinese health authorities select the former strategy for these CLL patients.

Selfie behavior and cosmetic surgery consideration in adolescents: the mediating roles of physical appearance comparisons and facial appearance concern.

Selfie activity may contribute to the acceptance of cosmetic surgery in adolescents, although few empirical studies exist. Based on social comparison theory, this study examined the association between selfie behavior and cosmetic surgery consideration among Chinese adolescents and further tested the possible mediating roles of social comparison and facial appearance concern in this relationship. A sample of 537 adolescents (339 girls and 198 boys) were recruited voluntarily to complete questionnaires on selfie behavior, upward physical appearance comparison, facial appearance concern and cosmetic surgery consideration. Linear regression and mediation analyses were conducted. The results showed that selfie behavior predicted higher level of adolescents' cosmetic surgery consideration. Moreover, this relationship was sequentially mediated through upward physical appearance comparison and facial appearance concern. These findings expand the existent literature by suggesting that selfie behavior may trigger upward social comparison in adolescents, which in turn increase their acceptance of cosmetic surgery.

The economic research of arsenic trioxide for the treatment of newly diagnosed acute promyelocytic leukemia in China.

BACKGROUND: The objective of this study was to conduct the first systematic evaluation of the long-term economic impact of arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) from the perspective of the Chinese health care system. METHODS: On the basis of clinical data from a randomized phase 3 trial, a time-dependent Markov model with 4 health states (complete remission, relapse or treatment failure, post-treatment failure, and death) was used to evaluate the incremental costs per quality-adjusted life-year (QALY) gained from the ATO plus ATRA regimen compared with the ATRA plus chemotherapy (CT) regimen over a 30-year period. All costs were adjusted to 2018 levels based on the Chinese Consumer Price Index. Both costs and health outcomes were discounted by 3% annually. One-way sensitivity analysis and probability sensitivity analysis were performed. RESULTS: Compared with the ATRA plus CT strategy, the ATO plus ATRA strategy was associated with 1.38 additional QALYs gained and $392.05 (estimated in 2018 US dollars) in incremental costs per patient over 30 years. Consequently, the incremental cost-effectiveness ratio was $284.02 per QALY gained, which was far below the Chinese willingness-to-pay threshold of $29,306 per QALY gained. Sensitivity analyses demonstrated the robustness of these results. CONCLUSIONS: From the perspective of the Chinese health care system, the ATO plus ATRA strategy is cost-effective for patients with newly diagnosed APL compared with the ATRA plus CT strategy. Therefore, the authors strongly suggest that China's health authorities choose the former strategy for these patients, whether for the elderly or for young people.

Effects of trait fear of pain on event-related potentials during word cue presentations that signal potential pain.

People who are especially afraid of pain may display attention biases that increase their risk for developing chronic pain following an injury. However, specific neurophysiological mechanisms underlying associations between elevated trait fear of pain levels and environmental cues that signal potential pain experiences are not well understood. To address this gap, event-related potentials (ERPs) were recorded among 39 high pain-fearful (H-FOP) and 36 low pain-fearful (L-FOP) adults exposed to potentially painful somatosensory stimulation cued by sensory pain words versus non-painful stimulation cued by neutral words. H-FOP group members displayed slower reaction times in judging somatosensory stimulation and rated stimulation to be more intense than L-FOP group members did. H-FOP group members also exhibited comparatively earlier peak latencies of P2 and N2 components during word cue presentations as well as weaker P3 amplitudes in processing non-painful stimulation cued by sensory pain words. These findings suggested that, among the high trait pain-fearful, exposure to word cues signaling potential pain results in the allocation of fewer cognitive resources toward processing somatosensory stimuli that are not actually painful.

Association of functional variant in GDF1 promoter with risk of congenital heart disease and its regulation by Nkx2.5.

GDF1 plays an important role in left-right patterning and genetic mutations in the coding region of GDF1 are associated with congenital heart disease (CHD). However, the genetic variation in the promoter of GDF1 with sporadic CHD and its expression regulation is little known. The association of the genetic variation in GDF1 promoter with CHD was examined in two case-control studies, including 1084 cases and 1198 controls in the first study and 582 cases and 615 controls in the second study. We identified one single nucleotide polymorphism (SNP) rs181317402 and two novel genetic mutations located in the promoter region of GDF1. Analysis of combined samples revealed a significant association in genotype and allele frequencies of rs181317402 T/G polymorphism between CHD cases in overall or ventricular septal defects or Tetralogy of Fallot and the control group. rs181317402 allele G polymorphism was significantly associated with a decreased risk of CHD. Furthermore, luciferase assay, chromatin immunoprecipitation and DNA pulldown assay indicated that Nkx2.5 transactivated the expression of GDF1 by binding to the promoter of GDF1. Luciferase activity assay showed that rs181317402 allele G significantly increased the basal and Nkx2.5-mediated activity of GDF1 promoter, while the two genetic mutations had the opposite effect. rs181317402 TG genotype was associated with significantly increased mRNA level of GDF1 compared with TT genotype in 18 CHD individuals. Our results demonstrate for the first time that Nkx2.5 acts upstream of GDF1 and the genetic variants in GDF1 promoter may confer genetic susceptibility to sporadic CHD potentially by altering its expression.

Approach and inhibition responses to external food cues among average-weight women who binge eat and weight-matched controls.

Despite laboratory evidence linking impulsivity to binge-eating (BE) among people with obesity, it is unclear whether such inhibitory control deficits extend to average-weight persons who binge eat or influence actual calories consumed when such opportunities present. Towards clarifying these issues, women with higher (n = 31) and lower (n = 31) BE levels engaged in a visual Go/No-Go task comprising images of high-calorie foods, low-calorie foods, and household objects, after which they completed a self-report battery in an environment conducive to snacking. Analyses indicated these groups did not differ in task-based false alarm rates (i.e., responding when response inhibition was required) but the higher BE group reported more trait-based impulsivity, was faster and more accurate in responding to "Go" trials involving high-calorie food images, and was more likely to eat at least one snack during post-task questionnaire completion. Within the entire sample, faster "Go" trial reaction times and higher false alarm rates across image types predicted higher post-task calorie intake levels while BE status and trait impulsivity did not. In sum, average weight women who binge eat were more responsive to high calorie food cues but showed no evidence of behavioral inhibitory control deficits compared to weight-matched controls.

High-Sensitivity Encoder-Like Micro Area-Changed Capacitive Transducer for a Nano-g Micro Accelerometer.

Encoder-like micro area-changed capacitive transducers are advantageous in terms of their better linearity and larger dynamic range compared to gap-changed capacitive transducers. Such transducers have been widely applied in rectilinear and rotational position sensors, lab-on-a-chip applications and bio-sensors. However, a complete model accounting for both the parasitic capacitance and fringe effect in area-changed capacitive transducers has not yet been developed. This paper presents a complete model for this type of transducer applied to a high-resolution micro accelerometer that was verified by both simulations and experiments. A novel optimization method involving the insertion of photosensitive polyimide was used to reduce the parasitic capacitance, and the capacitor spacing was decreased to overcome the fringe effect. The sensitivity of the optimized transducer was approximately 46 pF/mm, which was nearly 40 times higher than that of our previous transducer. The displacement detection resolution was measured as 50 pm/√Hz at 0.1 Hz using a precise capacitance detection circuit. Then, the transducer was applied to a sandwich in-plane micro accelerometer, and the measured level of the accelerometer was approximately 30 ng/√Hz at 1Hz. The earthquake that occurred in Taiwan was also detected during a continuous gravity measurement.

Attention Disengagement Difficulties among Average Weight Women Who Binge Eat.

In this study, we assessed biases in attention disengagement among average-weight women with binge-eating (n = 33) and non-eating disordered controls (n = 31). Participants engaged in a spatial cueing paradigm task wherein they first observed high-calorie food, low-calorie food, or neutral images and then had to quickly locate targets in either the same or a different location. Within both groups, reaction times (RTs) were longer to valid-cued trials (i.e. target appearing in location of preceding cue) than to invalid-cued trials (i.e. targets appearing in location different from initial location), reflecting a general inhibition of return (IOR) effect. However, RT findings also indicated that women with BE had significantly more difficulty disengaging from high-calorie food images than did controls, even though neither group had disengagement problems related to other image types. Selective attention disengagement difficulties related to high-calorie food images suggested that increased reward sensitivity to such cues is related to binge eating risk. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Efficacy of kidney-tonifying traditional Chinese medicine prescriptions in hypoplastic uterus treatment: a systematic review and meta-analysis.

AIM: To review and evaluate the efficacy of kidney-tonifying traditional Chinese medicine prescriptions (KT-TCMP) in hypoplastic uterus (HU) treatment. METHODS: We searched MEDLINE, the Cochrane Library, CNKI (China National Knowledge Infrastructure), WANFANG and VIP databases until 14 December 2013 independently with two investigators. Randomized controlled trials (RCT) involving KT-TCMP as a combined or monotherapy in the treatment of HU were reviewed and analyzed. Meta-analysis was performed by Review Manager (version 5.2). RESULTS: Nine RCT of 1745 patients were eligible for this review and meta-analysis, of which eight RCT described the primary outcome of clinical efficacy and three RCT drew the secondary outcome of uterine size. Meta-analyzed 'recovery' clinical efficacy of KT-TCMP in seven RCT was conducted which considered diethylstilbestrol therapy alone as control, as well as three RCT that meta-analyzed the effect of KT-TCMP on uterine diameter enlargement. As a result, KT-TCMP therapy had a significantly improved difference in increasing 'recovery' clinical efficacy (risk ratio, 2.34; 95% confidence interval [CI], 1.90-2.89) and enlarging the uterine diameter (standardized mean difference, 1.62; 95% CI, 1.39-1.84). One study reported adverse reactions as an important outcome and found it was safe during KT-TCMP therapy. CONCLUSION: The therapy of applying KT-TCMP as a combined or monotherapy in the treatment of HU may be more efficacious. However, these RCT were of moderate methodological quality and small sample size; thus, the results should be confirmed with more rigorously controlled further studies.

Expression of Glutathione Peroxidase4 in Patients with Esophageal Squamous Carcinoma and Its Impact on the Radiosensitivity of Esophageal Squamous Carcinoma.

OBJECTIVE: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity. METHOD: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC. RESULTS: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure. CONCLUSION: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.

Single-cell RNA sequencing indicates cordycepin remodels the tumor immune microenvironment to enhance TIGIT blockade's anti-tumor effect in colon cancer.

Both preclinical and clinical studies have extensively proven the effectiveness of TIGIT inhibitors in tumor immunotherapy. However, it has been discovered that the presence of CD226 on tumor-infiltrating lymphocytes is crucial for the effectiveness of both anti-TIGIT therapy alone and when combined with anti-PD-1 therapy for tumors. In our investigation, we observed that cordycepin therapy significantly augmented the expression of the Cd226 gene. As a result, it was hypothesized that cordycepin therapy could enhance the effectiveness of anti-TIGIT therapy. By employing single-cell RNA sequencing analysis of immune cells in the MC38 tumor model, we discovered that cordycepin combined with anti-TIGIT therapy led to a significant increase in the proportion of NK cells within the tumor immune microenvironment. This increased NK cell activity and decreased the expression of inhibitory receptors and exhaustion marker genes. In the combination therapy group, CD8+ T cells had lower exhaustion state scores and increased cytotoxicity, indicating a better immune response. The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4+ T cell and CD8+ T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.

Visual conservation treatment dilemmas in neuroblastoma with bilateral blindness.

OBJECTIVE: To investigate the clinical features, treatment strategies, and prognosis of neuroblastoma with bilateral blindness. METHODS: The clinical data of five patients with bilateral blindness neuroblastoma admitted to Beijing Children's Hospital from April 2018 to September 2020 were retrospectively collected to summarize their clinical characteristics. RESULTS: All patients were female and the median age at presentation was 25 (23, 41) months. The median intervention time from the onset of symptoms of bilateral blindness to the start of treatment was 10 (10, 12) days. All five cases were staged as stage M and grouped as high risk. Four cases were MYCN gene amplification and one case was MYCN acquisition. Five children were treated according to a high-risk neuroblastoma treatment protocol. Four children did not recover their vision after treatment, and one case improved to have light perception. All patients were effectively followed up for a median of 20 (12, 31) months, with three deaths, one tumor-free survival, and one recurrent tumor-bearing survival. CONCLUSION: Neuroblastoma with bilateral blindness is rare in the clinic, mostly in children of young age, and is often associated with MYCN amplification and multiple metastases. Early hormone shock therapy and optic nerve decompression are beneficial for preserving the child's vision. A joint multi-disciplinary treatment may help in the formulation of treatment decisions. Achieving a balance between good visual preservation and survival within the short optic nerve neurotherapeutic window is extremely challenging.

Social Comparison and Female Adolescents' Selfie Behaviors: Body Surveillance as the Mediator and Self-Esteem as the Moderator.

The current study aimed to examine whether body surveillance mediated the relation between social comparison and selfie behaviors, and whether this mediating process was moderated by self-esteem. A sample of 339 female adolescents were recruited to participate in the present study and completed self-report measures of selfie behaviors, upward and downward appearance comparisons with peers, self-objectification and self-esteem. Results indicated that body surveillance mediated the association between upward physical appearance comparison and selfie behaviors. In addition, self-esteem moderated the relation between body surveillance and selfie behaviors. These findings add to the extant literature by suggesting that selfies may be some new ways of body surveillance and physical appearance comparison, which have some theoretical and practical implications.

The role of AIM2 in human hepatocellular carcinoma and its clinical significance.

BACKGROUND: AIM2 (absent in melanoma 2) was first discovered as the gene which was not expressed in melanoma cells. It is established that the AIM2 inflammasome function as the double-stranded DNA (dsDNA) sensor, and it plays a crucial role in infectious disorders and cancer. Little is known about the AIM2 expression pattern and its clinical significance in human hepatocellular carcinoma (HCC), understating how AIM2 altered the HCC cells is of high clinical interest. METHODS: Immunohistochemistry was performed to investigate the AIM2 expression in HCC tissues. Then we constructed the ectopic AIM2-expressed HCC cell line by lentiviral transduction. Biological functional assays were used to analyze the clinical significance of AIM2. RESULTS: AIM2 expression was significantly decreased in human HCC tissues compared with adjacent normal tissues, and the overall survival of HCC patients with higher AIM2 expression was significantly better. Ectopic expression of AIM2 in HCC cells significantly inhibited migration and promoted apoptosis. Furthermore, our study revealed that the notch signaling pathway could be involved in the regulation of AIM2 in the cellular network in HCC cells. AIM2 delayed the tumor progression and correlated with immune cell infiltration. CONCLUSION: In this study, we suggested AIM2 played an inhibitory role in regulating the growth and metastasis of HCC, which supported the notion that AIM2 could serve as a potential therapeutic target for HCC.

Small change for big improvement in the preparation of the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir.

In this study, the key intermediate N 1, N 3-disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from S-ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and N 1-alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key N 1, N 3-disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs.

DpdtpA, A Multi-metal Ion Chelator, Attenuates Tau Phosphorylation and Microglial Inflammatory Response via Regulating the PI3K/AKT/GSK-3ß Signal Pathways.

Tau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tau-induced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-κB and production of inflammatory cytokines, IL-1ß, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3ß (GSK-3ß) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3ß signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.

The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors.

As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency ablation (RFA) side by analyzing single-cell RNA sequencing (scRNA-seq) data of tumor-bearing mice compared with control tumors. We showed that ablation treatment could increase the proportion of CD8+T cells and the interaction between macrophages and T cells was altered. Another thermal ablation treatment, microwave ablation (MWA), increased the enrichment of signaling pathways for chemotaxis and chemokine response and was associated with the chemokine CXCL10. In addition, the immune checkpoint PD-1 was especially up-regulated in the infiltrating T cells of tumors on the non-ablation side after thermal ablation treatment. Combination therapy of ablation and PD-1 blockade had a synergistic anti-tumor effect. Furthermore, we found that the CXCL10/CXCR3 axis contributed to the therapeutic efficacy of ablation combined with anti-PD-1 therapy, and activation of the CXCL10/CXCR3 signaling pathway might improve the synergistic effect of this combination treatment against solid tumors.

Why do selfies increase young women's willingness to consider cosmetic surgery in China? The mediating roles of body surveillance and body shame.

The present study was designed to examine a possible two mediator model with both body surveillance and body shame mediating the association of selfie behavior with cosmetic surgery consideration in young adult women. A sample of 588 young adult women participated in this study and completed questionnaires regarding selfie behavior, body surveillance, body shame, and cosmetic surgery consideration. Results indicated that selfie behavior was positively related to cosmetic surgery consideration. In addition, the mediation analysis by PROCESS revealed that body surveillance and body shame mediated the relation between selfie behavior and cosmetic surgery consideration. These findings add to the extant literature by suggesting that selfie behavior may be a new experience of self-objectification, which provide new insights into the relation between selfie activities and cosmetic surgery consideration in young women.

Multi-Grid Capacitive Transducers for Measuring the Surface Profile of Silicon Wafers.

The measurements of wafers' surface profile are crucial for safeguarding the fabrication quality of integrated circuits and MEMS devices. The current techniques measure the profile mainly by moving a capacitive or optical spacing sensing probe along multiple lines, which is high-cost and inefficient. This paper presents the calculation, simulation and experiment of a method for measuring the surface profile with arrayed capacitive spacing transducers. The calculation agreed well with the simulation and experiment. Finally, the proposed method was utilized for measuring the profile of a silicon wafer. The result is consistent with that measured by a commercial instrument. As a movement system is not required, the proposed method is promising for industry applications with superior cost and efficiency to the existing technology.