Research of the dynamic regulatory mechanism of Compound Danshen Dripping Pills on myocardial infarction based on metabolic trajectory analysis.

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PURPOSE: It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. METHODS: The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. RESULTS: CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. CONCLUSION: The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.

Renal toxicity of Aconitum plants? A study based on a new mass spectrometry scanning strategy and computer virtual screening.

BACKGROUND: Radix Aconiti Lateralis (Fuzi), a mono-herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining-virtual multi-target screening-active component prediction-literature verification" to screen potential nephrotoxic substances rapidly. METHOD: The UHPLC-Q-Exactive-Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro-in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein-protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi-induced nephrotoxicity was screened. RESULTS: Eighty-one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. CONCLUSIONS: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi.

IL-4-induced decrease in both the number and CTLA-4 expression of Treg impairs suppression of Th2 type inflammation in severe atopic dermatitis.

BACKGROUND: Treg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of Treg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. OBJECTIVE: This study aims to investigate the molecular mechanism underlying quantitative and functional changes of Treg in AD. METHODS: The molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD. RESULTS: Increased proportion of Treg was detected in mild and moderate AD. Conversely, characteristic decrease in both the number and CTLA-4 expression of Treg was relevant to serum IL-4 level in severe AD patients, which was verified under a high concentration of IL-4 treatment in vitro. The underlying mechanism is that IL-4/pSTAT6 pathway recruits DNMT1 and HDAC2 to inhibit transcriptional regulation of Foxp3 and CTLA-4 loci. High level of IL-4 impaired the suppression of Treg against Th2 cell differentiation mediated by CTLA-4, and blockade of IL-4Rα signaling in Treg restored Treg number and suppression of Th2 cell in AD model mice and patients with AD. CONCLUSION: The number of Treg is relevant to stratification of severity and serum IL-4 level in patients with AD. Abnormal high level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of Treg. The reduced expression of CTLA-4 on Treg induced by IL-4 impairs suppression of Th2 cell differentiation.

Media representations of China's inclusive education: A corpus-assisted critical discourse analysis.

The Chinese government aspires for inclusive education to serve as an exemplary model in addressing educational inequity issues and establishing a responsible global image as a major power. Nevertheless, there has been limited focus on China's news media coverage concerning its inclusive education initiatives aimed at international audiences. To bridge this gap, this study employed a corpus-assisted critical discourse analytic approach to examine China's self-image in relation to its inclusive education endeavours. Seventy-three English-language news articles from the official channel were retrieved for meticulous line-by-line concordance analysis. The results indicate that out of the 520 co-occurring instances, they can be broadly categorised into four groups: efforts to develop inclusive education (65.4%); consensus on benefits of inclusive education (24.5%); challenges faced by inclusive education (4.8%); and others (5.4%). This study illuminates the effective utilisation of official media in the image construction of inclusive education in China.

A bibliometric analysis of literatures on uterine leiomyosarcoma in the last 20 years.

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS. Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed us to pinpoint research hotspots and create visual representations, resulting in the retrieval of 2489 pertinent articles. Results: This literature review covers 2489 articles on uterine leiomyosarcoma (uLMS) from the past 20 years. Key findings include an average annual publication rate of 8.75, with a 6.07% yearly growth rate and an average citation count of 17.22. Core+Zone 2 sources contributed 1079 articles and 207 reviews, displaying a 4.98% annual growth rate. The analysis identified top journals, influential authors, and core sources, such as the prevalence of publications from the United States and the dominance of GYNECOLOGIC ONCOLOGY and HENSLEY ML. Bradford's Law and Lotka's Law highlighted core sources and author productivity, respectively. Thematic mapping and factorial analysis revealed research clusters, including etiology, diagnosis, treatment advancements, and surgical approaches, with prominent themes such as gemcitabine and docetaxel. Overall, this comprehensive analysis provides insights into uLMS literature trends and influential factors. Conclusion: This thorough bibliometric analysis, in its whole, illuminates the field's guiding principles while also revealing the subtle patterns within the uLMS literature. The knowledge gained here contributes to the current discussion in uLMS and related scientific fields and provides a solid basis for future research paths.

Arecoline-Induced Hepatotoxicity in Rats: Screening of Abnormal Metabolic Markers and Potential Mechanisms.

Arecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.

A retrospective observational study on maternal and neonatal outcomes of COVID-19: Does the mild SARS-CoV-2 infection affect the outcome?

Background: Currently, several SARS-CoV-2 variants, including Omicron, are still circulating globally. This underscores the necessity for a comprehensive understanding of their impact on obstetric and neonatal outcomes in pregnant women, even in cases of mild infection. Methods: We conducted a retrospective, single-center observational study to investigate the association between gestational SARS-CoV-2 infection and maternal-fetal outcomes in the Chinese population. The study enrolled 311 pregnant patients with SARS-CoV-2 infection (exposure group) and 205 uninfected pregnant patients (control group). We scrutinized the hospital records to collect data on demographics, clinical characteristics, and maternal and neonatal outcomes for subsequently comparison. Results: Similar characteristics were observed in both groups, including maternal age, height, BMI, gravidity, parity, and comorbidities (p > 0.05). A majority (97.4%) of pregnant women in the exposure group with COVID-19 experienced mild clinical symptoms, with fever (86.5%) and cough (74.3%) as the primary symptoms. The exposure group exhibited significantly higher incidences of cesarean section and fetal distress compared to the control group (p < 0.05). Furthermore, pregnant women in the exposure group showed reduced levels of hemoglobin and high-sensitivity C-reactive protein, while experiencing significantly increased levels of lymphocytes, prothrombin time, alanine aminotransferase, and aspartate aminotransferase (p < 0.05). Notably, recent SARS-CoV-2 infection prior to delivery appeared to have an adverse impact on liver function, blood and coagulation levels in pregnant women. When comparing the two groups, there were no significant differences in the postpartum hemorrhage rate, premature birth rate, birth weight, neonatal asphyxia rate, neonatal department transfer rate, and neonatal pneumonia incidence. Conclusions: Our study suggests that mild COVID-19 infection during pregnancy does not have detrimental effects on maternal and neonatal outcomes. However, the increased risks of events such as fetal distress and cesarean section, coupled with potential alterations in physical function, reveal the consequences of SARS-CoV-2 infection during pregnancy, even in mild cases. These findings emphasize the importance of proactive management and monitoring of pregnant individuals with COVID-19.

Imaging analysis of the biological parameters of the lens in patients with cortical age-related cataracts using ultrasound biomicroscopy.

BACKGROUND: The spatial position of the lens in patients with cortical age-related cataract (CARC) is unclear. We investigated a basis for the assessment of visual quality after cataract surgery by analysing the ultrasound biomicroscopic characteristics of the biological parameters of the lens in patients with CARC. METHODS: In this retrospective study, 119 patients (50 males and 69 females, totalling 238 eyes) with CARC who underwent simple cataract surgery were selected. The lens thickness (LT), axial length (AL), anterior chamber depth (ACD), lens vault (LV), trabecular-iris angle (TIA), iris-lens angle (ILA), iris-lens contact distance (ILCD) were measured by A-scan ultrasound and ultrasound biomicroscopy. The corresponding lens position (LP) and relative lens position (RLP) were calculated. RESULTS: LP was greater in men than in women (P < 0.05), LV was smaller in men than in women (P = 0.002), ILA and ILCD were not statistically significant (P = 0.072 and P = 0.854, respectively). There were significant differences in TIA, ILA, and ILCD in the four quadrants (all P < 0.05), with a trend in the distribution of TIA: superior < inferior < nasal < temporal, ILA: nasal < inferior < temporal < superior, and ILCD: superior < temporal < inferior < nasal. CONCLUSIONS: The lens protrudes more obviously in females than in males and the lens tilts to a certain extent with the increase of age and tends to be more upward and temporal in the supine position. Therefore, trends in lens-related parameters in patients with CARC should be taken seriously.

Turnover intention and coping strategies among older nursing assistants in China: a qualitative study.

Introduction: With the increasing aging population, older nursing assistants have made significant contributions to institutional eldercare. However, there is a high turnover rate among these workers, and it is crucial to address this issue and find ways to stabilize the workforce. This study aimed to explore the factors influencing turnover intention and coping strategies among older nursing assistants, in order to provide targeted assistance and guidance to reduce their intention to resign and ultimately lower the turnover rate. Methods: Qualitative research methods were employed to conduct semi-structured interviews with older nursing assistants in Changsha. The data obtained from these interviews were then analyzed using a phenomenological analysis approach and NVIVO (QSR International, Doncaster, Australia) software version 11.0. Results: It is found that several factors influence turnover intention among older nursing assistants. Which include work pay, work environment, professional identity, external motivation, and work pressure. Additionally, the coping strategies employed by these individuals in relation to their intention to resign include self-regulation, seeking support, self-improvement, and exploring motivation. Discussion: It is also evident from our study that reducing the turnover intention of older nursing assistants requires a collaborative effort from older adult care institutions, functional departments, and eldercare nursing assistants themselves. By addressing the factors influencing turnover intention and providing support and resources for coping strategies, we can work towards stabilizing the workforce and improving institutional eldercare.

[Simultaneous determination of 36 mycotoxins in fruits by QuEChERS coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Mycotoxins are secondary metabolites produced by toxigenic fungi under specific environmental conditions. Fruits, owing to their high moisture content, rich nutrition, and improper harvest or storage conditions, are highly susceptible to various mycotoxins, such as ochratoxin A (OTA), zearalenone (ZEN), patulin (PAT), Alternaria toxins, etc. These mycotoxins can cause acute and chronic toxic effects (teratogenicity, mutagenicity, and carcinogenicity, etc) in animals and humans. Given the high toxicity and wide prevalence of mycotoxins, establishing an efficient analytical method to detect multiple mycotoxins simultaneously in different types of fruits is of great importance. Conventional mycotoxin detection methods rely on high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). However, fruit sample matrices contain large amounts of pigments, cellulose, and minerals, all of which dramatically impede the detection of trace mycotoxins in fruits. Therefore, the efficient enrichment and purification of multiple mycotoxins in fruit samples is crucial before instrumental analysis. In this study, a reliable method based on a QuEChERs sample preparation approach coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to determine 36 mycotoxins in fruits. In the optimal extraction method, 2.0 g of a sample was extracted with 10 mL of acetic acid-acetonitrile-water (1∶79∶20, v/v/v) in a 50 mL centrifuge tube, vortexed for 30 s, and ultrasonicated for 40 min. The mixture was then salted out with 2.0 g of anhydrous MgSO4 and 0.5 g of NaCl and centrifuged for 5 min. Next, 6 mL of the supernatant was purified using 85 mg of octadecylsilane-bonded silica gel (C18) and 15 mg of N-propylethylenediamine (PSA). After vigorous shaking and centrifugation, the supernatant was collected and dried with nitrogen at 40 ℃. Finally, the residues were redissolved in 1 mL of 5 mmol/L ammonium acetate aqueous solution-acetonitrile (50∶50, v/v) and passed through a 0.22 µm nylon filter before analysis. The mycotoxins were separated on a Waters XBridge BEH C18 column using a binary gradient mixture of ammonium acetate aqueous solution and methanol. The injection volume was 3 µL. The mycotoxins were analyzed in multiple reaction monitoring (MRM) mode under both positive and negative electrospray ionization. Quantitative analysis was performed using an external standard method with matrix-matched calibration curves. Under optimal conditions, good linear relationships were obtained in the respective linear ranges, with correlation coefficients (R2) no less than 0.990. The limits of detection (LODs) and quantification (LOQs) were 0.02-5 and 0.1-10 µg/kg, respectively. The recoveries of the 36 mycotoxins in fruits ranged from 77.0% to 118.9% at low, medium, and high spiked levels, with intra- and inter-day precisions in the range of 1.3%-14.9% and 0.2%-17.3%, respectively. The validated approach was employed to investigate mycotoxin contamination in actual fruit samples, including strawberry, grape, pear, and peach (15 samples of each type). Eleven mycotoxins, namely, altenuene (ALT), altenusin (ALS), alternariol-methyl ether (AME), tenuazonic acid (TeA), tentoxin (Ten), OTA, beauvericin (BEA), PAT, zearalanone (ZAN), T-2 toxin (T2), and mycophenolic acid (MPA), were found in the samples; three samples were contaminated with multiple mycotoxins. The incidence rates of mycotoxins in strawberry, grape, pear, and peach were 27%, 40%, 40%, and 33%, respectively. In particular, Alternaria toxins were the most frequently found mycotoxins in these fruits, with an incidence of 15%. The proposed method is simple, rapid, accurate, sensitive, reproducible, and stable; thus, it is suitable for the simultaneous detection of the 36 mycotoxins in different fruits.

The application of HER2 and CD47 CAR-macrophage in ovarian cancer.

BACKGROUND: The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer. METHODS: In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M. RESULTS: We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8+ cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8+ T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression. CONCLUSIONS: We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment.

Differences Between Angle Configurations in Different Body Positions by Ultrasound Biomicroscopy in Patients with Cortical Age-Related Cataract.

Purpose: To investigate the differences in parameters related to angle configuration and lens position in patients with cortical age-related cataract by ultrasound biomicroscopy (UBM) in different body positions. Methods: Prospective study with 55 patients with cortical age-related cataract proposed for phacoemulsification, examined using a Compact Touch STS UBM (Quantel Medical, France). UBM bag/balloon technology was applied to measure the central anterior chamber depth (ACD) and lens vault (LV) in horizontal and vertical orientation in sitting and supine positions, angle opening distance (AOD500), trabecular iris angle (TIA) and iris lens angle (ILA) in four quadrants: superior, inferior, nasal, and temporal. Results: We found no significant difference in ACD between sitting and supine positions (p = 0.053); LV was significantly greater in the supine position (p < 0.001); AOD500 in superior and inferior quadrants were significantly longer in the sitting position (p = 0.001; p < 0.001); TIA in superior and inferior quadrants was significantly greater in the sitting position (p < 0.001; p < 0.001), and TIAmax-min was significantly smaller in the sitting position (p = 0.001); ILA in temporal quadrant was significantly larger in the sitting position (p = 0.015) and ILAmax-min was significantly smaller in the sitting position (p < 0.001). Conclusion: The anterior chamber angle was narrower and the lens was positioned more anteriorly in the supine than in the sitting position in cortical age-related cataract. Different positions may affect the angle configuration and the relative space of lens through different directions of mechanics and modes of action.

The Role of CTNNA1 in Malignancies: An Updated Review.

Catenin alpha 1 (CTNNA1), encoding α-catenin, is involved in several physiological activities, such as adherens junction synthesis and signal transduction. Recent studies have suggested additional functions for CTNNA1 malignancies. This review systematically summarizes the varying functions of CTNNA1 in different tumors and briefly describes the diverse pathways and mechanisms involved in different types of tumors. CTNNA1 is abnormally expressed in leukemia and solid tumor such as cancers of digestive system, genitourinary system and breast, and it's related to the occurrence, development, and prognosis of tumors. In addition, the possible physiological processes involving CTNNA1, such as methylation, miRNA interference, or regulatory axes, similar to those of CDH1, SETD2, and hsa-miR-30d-5p/GJA1 are also summarized here. The precise mechanism of CTNNA1 in most cancers remains uncertain; hence, additional pre-clinical studies of CTNNA1 are warranted for potential early tumor diagnosis, prognosis, and treatment.

Recent Updates on the Role of the MicroRNA-10 Family in Gynecological Malignancies.

The ever-increasing morbidity associated with gynecological malignancies constantly endangers the physical and psychological health of women. Since a long time, there has been an urgent need for a deeper understanding of the tumorigenesis and the development of gynecological cancer to identify new molecular markers for early diagnosis and metastatic disease prognosis and for the development of therapeutic targets. MicroRNAs are crucial cellular regulators. The microRNA-10 (miR-10) family has been found to play an integral role in the evolution of numerous cancer types. A comprehensive understanding of current studies on miR-10 could provide better insights into future research and clinical applications in related fields. This article reviews the latest research on the role of the miR-10 family in gynecological malignancies and the relevant molecular mechanism, mainly focusing on endometrial, cervical, and ovarian cancers.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

The role of a key transcription factor PU.1 in autoimmune diseases.

PU.1, a transcription factor member of the E26 transformation-specific family, affects the function of a variety of immune cells in several physiological and pathological conditions. Previous studies studying the role of PU.1 in pathological conditions have mainly focused on immune system-related cancers, and a series of articles have confirmed that PU.1 mutation can induce a variety of immune cell-related malignancies. The underlying mechanism has also been extensively validated. However, the role of PU.1 in other major immune system-related diseases, namely, systemic autoimmune diseases, is still unclear. It was only in recent years that researchers began to gradually realize that PU.1 also played an important role in a variety of autoimmune diseases, such as rheumatoid arthritis (RA), experimental autoimmune encephalomyelitis (EAE) and systemic lupus erythematosus (SLE). This review article summarizes the findings of recent studies that investigated the role of PU.1 in various autoimmune diseases and the related underlying mechanisms. Furthermore, it presents new ideas and provides insight into the role of PU.1 as a potential treatment target for autoimmune diseases and highlights existing research problems and future research directions in related fields.

[Meta analysis of acupuncture and moxibustion for anxiety and depression in irritable bowel syndrome].

OBJECTIVE: To evaluate the effectiveness of acupuncture and moxibustion in the treatment of anxiety and depression in irritable bowel syndrome (IBS) by meta-analysis. METHODS: China National Knowledge Infrastructure (CNKI), Wanfang Data, China Scientific Journal Database (VIP), China Biomedical Literature Service System (SinoMed), PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) on acupuncture and moxibustion in the treatment of IBS anxiety and depression from database inception to June 30, 2021. RevMan5.3 and Stata16.0 were used to conduct Meta-analysis of relevant outcome indicators. RESULTS: A total of 11 RCTs were included in this study, involving 774 IBS patients (431 in the intervention group and 343 in the control group). Eight of them used manual acupuncture (MA) intervention, and the other three used electroacupuncture (EA) intervention. Meta-analysis showed that compared with the western medicine, MA improved the sedation-agitation scale (SAS) scores (MD=5.24, 95%CI=ï¼»3.49, 7.00ï¼½, P<0.000 01) and self-rating depression scale (SDS) scores (MD=8.50, 95%CI=ï¼»4.68, 12.32ï¼½, P<0.000 1) in IBS patients, and there was no significant difference between MA or EA and western medicine in the improvement of Hamilton anxiety rating scale (HAMA) scores (MD=1.10, 95%CI=ï¼»0.36, 2.56ï¼½, P=0.14) and Hamilton depression rating scale (HAMD) scores (MD=0.53, 95%CI=ï¼»0.89, 1.94ï¼½, P=0.47). In terms of total effective rates (RR=1.21, 95%CI=ï¼»1.12, 1.31ï¼½, P<0.000 01) and the irritable bowel syndrome severity scoring system (IBS-SSS) scores (MD=42.16, 95%CI=ï¼»27.40, 56.91ï¼½, P<0.000 01), both MA and EA therapy was superior to western medicine in alleviating gastrointestinal symptoms of IBS patients. CONCLUSION: MA and EA can improve the anxiety and depression of IBS patients, while the influence of other acupuncture and moxibustion interventions needs to be deeply explored with more high-quality RCTs.

ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer.

Adenosine (A)-to-inosine (I) RNA editing is the most prevalent RNA editing mechanism, in which adenosine deaminase acting on RNA 1 (ADAR1) is a major adenosine deaminase. Increasing evidence suggests that editing dysregulation of ADAR1 plays an important role in human tumorigenesis, while the underlying mechanism remains elusive. Here, we demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients. Importantly, silence of ADAR1 repressed ovarian cancer cell growth and colony formation in vitro and inhibited ovarian cancer cell tumorigenesis in vivo. Further cell cycle and transcriptome profile analysis revealed that silence of ADAR1 in ovarian cancer cells induced cell cycle arrest at G1/G0 stage. Mechanistically, loss of ADAR1 caused R-loop abnormal accumulation, thereby contributing to single stand DNA break and ATR pathway activation. Additionally, ADAR1 interacted with DHX9 to regulate R-loop complex formation, and A-to-I editing of nascent RNA repressed R-loop formation during co-transcriptional process. Together, our results identify a novel ADAR1/R-loop/ATR axis critical for ovarian cancer progression and a potential target for ovarian cancer therapy.

Comparison of Ocular Morphological Parameters Related to Lens Position by Anterior Segment Optical Coherence Tomography and Ultrasound Biomicroscopy.

Objective: The objective is to compare parameters related to lens position measured using anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in patients with senile cataract and perform a consistency analysis. Methods: This prospective study included 102 patients (102 eyes) scheduled for simple cataract surgery. Among the total patients, 44 were men, and 58 were women. AS-OCT (sitting) and UBM (lying) were used to measure the anterior chamber depth (ACD) in horizontal and vertical orientations and the iris-lens contact distance (ILCD) and iris-lens angle (ILA) in inferior, superior, nasal, and temporal quadrants. Paired-sample t-test was used to compare ACD, ILCD, and ILA measurements of the two methods, while Pearson's linear correlation and Bland-Altman analyses were used to analyze the correlation and consistency of the two results. Results: The horizontal (2.499 ± 0.464 mm) and vertical (2.531 ± 0.463 mm) ACD measured using AS-OCT and the horizontal (2.556 ± 0.467 mm) and vertical (2.563 ± 0.479 mm) ACD measured using UBM were significantly different (P < 0.001); moreover, the results showed good correlation and agreement. A significant difference was observed between the two methods in terms of ILCD measured in inferior, superior, nasal, and temporal quadrants (P < 0.001), and a significant correlation was found between measurements of both methods (P < 0.001). Approximately 3.92% (4/102), 0.98% (1/102), 3.92% (4/102), and 2.94% (3/102) of points were outside the 95% limits of agreement in the four quadrants, respectively, and the agreement of the results was good. ILA measured using both methods differed in inferior, superior, nasal, and temporal quadrants (P=0.003, 0.011, 0.001, 0.001, respectively), and the correlation was good (P < 0.001). The percentage of points outside the 95% limit was higher in inferior, superior, nasal, and temporal quadrants (4.90% (5/102), 5.88% (6/102), 5.88% (6/102), and 6.86% (7/102)) with poor agreement of the results. Conclusions: The correlation between AS-OCT and UBM in terms of measuring lens position-related parameters was good, but the agreement was unstable. The differences in measurement position (sitting and supine) and/or measurement methods (optics and ultrasound) may lead to variability in results.

Growth arrest-specific transcript 5 represses endometrial cancer development by promoting antitumor function of tumor-associated macrophages.

The tumor-suppressor role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been proven in various types of cancer. However, the specific function of GAS5 in tumor-associated macrophages (TAMs) of endometrial cancer (EC) is elusive. Quantitative PCR results showed that GAS5 expression decreased in EC tissues and primary TAMs from EC tumors. Tumor-associated macrophage infiltration was significantly positively associated with the developmental stage of EC. Direct coculture of GAS5-overexpressing TAMs and EC cells showed that GAS5 enhanced phagocytosis, antigen presentation, and activation of cytotoxic T cells, and repressed "Don't eat me" signals between TAMs and EC cells. Tumor formation in immunodeficient mice showed that GAS5-overexpressing macrophages could repress EC formation in vivo. GAS5 promoted M1 polarization by activating the microRNA-21- phosphatase and tensin homolog (PTEN)-AKT signaling pathway and directly repressing the nuclear accumulation and phosphorylation of oncogenic yes-associated protein 1 (YAP1) in TAMs. GAS5 inhibited the development of EC from both innate and adaptive immunity by transforming TAMs from a protumor to an antitumor phenotype. These antitumor effects of GAS5 on TAMs were mediated by the activation of the miR-21-PTEN-AKT pathway and inhibition of YAP1.