Transcription factor EHF drives cholangiocarcinoma development through transcriptional activation of glioma-associated oncogene homolog 1 and chemokine CCL2.

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS).

BACKGROUND: Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. METHODS: The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. CONCLUSIONS: The MOYAOMICS project represents a significant step toward comprehending MMD's molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

The Different Therapeutic Effects of Traditional Chinese Medicine Shensong Yangxin Capsule and Salubrinal in High-intensity Exercise-induced Heart Failure in Rats with Acute Myocardial Infarction.

BACKGROUND: Currently, endoplasmic reticulum stress is studied utilizing a dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia. However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart failure in myocardial tissue have not yet been investigated. OBJECTIVE: The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule (SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated. METHODS: Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group (AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week, echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and measure the percentage of apoptosis in each group; Western blotting was applied to detect the cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase SOD in serum. RESULTS: Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group were statistically significantly reduced, while LVESV were significantly higher, compared to those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately 21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably reduced in the AMI+Shensong group and AMI+Sal group， compared to the AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly lower, and MDA was significantly higher in the AMI+placebo group. Compared to the AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05) Conclusion: In rats with acute myocardial infarction in high-intensity exercise-induced heart failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction. SSYX has a shorter course of treatment and a better therapeutic effect than Sal.

Pan-cancer analysis of ABCC1 as a potential prognostic and immunological biomarker.

ABCC1 belongs to the ATP-binding cassette (ABC) superfamily, which encompasses a total of 48 constituent members. ABCC1 has been shown to be associated with the growth, progression, and drug resistance of various types of cancer. However, the impact of ABCC1 on cancer immune infiltration and pan-cancer prognosis has been rarely studied. Our comprehensive pan-cancer analysis unveiled elevated ABCC1 expression across various cancers. ABCC1 overexpression consistently predicted unfavorable outcomes based on TCGA data. Moreover, ABCC1 expression exhibited intricate associations with diverse immune-related genes and demonstrated a close correlation with immune scores across multiple tumor types. Analysis of scRNA-seq data from the GEO database revealed that the expression of ABCC1 in hepatocellular carcinoma (HCC) cells is significant positively correlated with macrophage infiltration. Furthermore, various in vitro and in vivo experiments substantiated the role of ABCC1 in promoting the progression of HCC, along with increased macrophage recruitment. Based on the results, we propose ABCC1 as a potentially valuable prognostic indicator and a prospective target for immune-based cancer therapies.

Contribution of Insulin Resistance and ß Cell Dysfunction to Gestational Diabetes Stratified for Pre-pregnant Body Mass Index.

The objective of the study was to evaluate the contribution of insulin resistance and ß cell dysfunction to gestational diabetes mellitus (GDM) in Chinese women stratified by pre-pregnant body mass index (BMI). A total of 847 pregnant women were enrolled. They were divided into low BMI and high BMI groups according to the median of pre-pregnancy BMI. The homeostasis model assessment of insulin resistance (HOMA-IR) and ß cell function (HOMA-ß), Matsuda index, and 60-min insulinogenic index (IGI60) were used to evaluate insulin resistance and ß cell function. In all the participants, 150 (17.71%) were diagnosed with GDM. ROC analyses showed that in the low BMI group, the association of ß cell dysfunction (IGI60 or HOMA-ß) with GDM was stronger than that of insulin resistance (Matsuda index or HOMA-IR), while in the high BMI group, the association of ß cell dysfunction with GDM was weaker than that of insulin resistance (all P < 0.05). Among all GDM patients, 47.33% demonstrated predominant insulin resistance (Matsuda index < 25th percentile), and 46% had predominant ß cell defect (IGI60 < 25th percentile). In the low BMI group, 15.09% of GDM patients demonstrated predominant insulin resistance, and 62.26% of GDM patients had predominant ß cell defect, whereas in the high BMI group, 64.95% of GDM patients demonstrated mainly insulin resistance and 36.08% of GDM patients had mainly ß cell defect. In women with low BMI, ß cell dysfunction is the major etiologic factor, whereas, in women with high BMI, insulin resistance is the predominant etiologic factor in the development of GDM.

Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects.

Blonanserin is a novel oral antischizophrenic drug. Under fasting (n = 50) and fed (n = 60) conditions, this study compared the bioequivalence of the generic blonanserin tablet with the reference blonanserin tablet. In this single-center, randomized, open-label, 2-period, 2-sequence, crossover study, 110 patients were randomly given a 4-mg dose of either the test or reference blonanserin tablet with a 14-day washout period. Blood samples were taken before performing and up to 72 hours following. A validated high-performance liquid chromatography-tandem mass spectrometry technique was used to measure the levels of blonanserin in plasma. Safety was evaluated throughout the study. The study found no significant differences in the maximum observed drug concentration in the plasma (Cmax ), the area under the plasma concentration-time curve from time 0 to the last sampling time (AUC0-t ), and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) between the 2 blonanserin formulations. The 90% confidence intervals of the geometric mean ratio of the test/reference formulations for Cmax , AUC0-t , and AUC0-∞ were within the 80%-125% limit. Food dramatically raised blonanserin exposure, and also significantly prolonged the lag time of absorption. No serious adverse events occurred. These results indicate that the 2 blonanserin formulations were bioequivalent and well tolerated in healthy Chinese subjects. In clinical treatment, it is necessary to consider the food effect of blonanserin.

Comparison of supercritical fluid chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry for the stereoselective analysis of chlorfenvinphos and dimethylvinphos in tobacco.

This study used reversed-phase liquid chromatography-tandem mass spectrometry and supercritical fluid chromatography-tandem mass spectrometry for determination of the stereoisomers of chlorfenvinphos and dimethylvinphos in tobacco. Tobacco samples were extracted and purified with a modified quick, easy, cheap, effective, rugged, and safe technique using spherical carbon. The performance of both methodologies was comprehensively compared in terms of methods validation parameters (separation efficiency, linearity, selectivity, recovery, repeatability, sensitivity, matrix effect, etc.). Under optimized conditions, the calibration curves of the stereoisomers of chlorfenvinphos and dimethylvinphos in the range of 10-500 ng/mL showed excellent linearity with R2 ≥ 0.997 in both methods. The adequate recoveries of analytes from three different spiked tobaccos were obtained using reversed-phase liquid chromatography-tandem mass spectrometry (86.1-95.7%) as well as supercritical fluid chromatography-tandem mass spectrometry (86.5-94.0%). The relative standard deviations for spiked samples were all below 7.0%. Compared with supercritical fluid chromatography-tandem mass spectrometry, lower matrix effects and LODs can be obtained in reversed-phase liquid chromatography-tandem mass spectrometry.

COVID-19 affects psychological symptoms of pregnant women indirectly by increasing their maternal concerns.

BACKGROUND: Pregnant women themselves are at higher risk for psychological symptoms. The impact of ongoing COVID-19 may increase the risk. However, it is uncertain whether COVID-19 affects pregnant women's psychological symptoms directly or indirectly being mediated. METHODS: This survey was conducted in four obstetrics and gynecology hospitals in Beijing from February 28, 2020, to April 26, 2020. Pregnant women who visited the antenatal-care clinic were mobilized to finish the online questionnaires, including the Generalized Anxiety Disorder 7-Item Scale, Patient Health Questionnaire-9, Connor-Davidson resilience scale, and Insomnia Severity Index. RESULTS: A total of 828 pregnant women were included in the analysis. The estimated self-reported rates of anxiety, depression, insomnia, and any of the three were 12.2 %, 24.3 %, 13.3 %, and 33.1 %, respectively. Mediating effect analysis showed that pregnant women's response to COVID-19 was not directly associated with psychological symptoms but indirectly through the mediating effect of maternal concerns, which accounted for 32.35 % of the total effect. Stratified analysis by psychological resilience showed that women's attitude toward COVID-19 (OR, 2.68, 95 % CI: 1.16-6.18) was associated with a higher risk of psychological symptoms in those with poor psychological resilience. LIMITATIONS: The study was a non-probability sampling survey, and the causal relationship between maternal concerns and psychological symptoms could not be determined due to the study's design. CONCLUSIONS: Under public health emergencies such as COVID-19, routine antenatal care should still be prioritized, and concerns related to childbirth-related caused by such emergencies should also be addressed, especially for those with weak psychological resilience.

Acute pancreatitis in pregnancy: a 10-year, multi-center, retrospective study in Beijing.

OBJECTIVE: Acute pancreatitis in pregnancy (APIP) is a rare and serious complication during pregnancy. It has acute onset and is difficult to diagnose and treat. The aim of the present study was to describe the etiology, clinical manifestations, and maternofetal outcomes of APIP. METHODS: We retrospectively reviewed 32 pregnant women who were treated at three tertiary care hospitals in Beijing, China. The correlation between the causes of APIP, severity, laboratory indices, and outcomes was analyzed. RESULTS: The most common causes of APIP were hypertriglyceridemia (56.2%,18/32) and gallstones (28.1%, 9/32). Hypertriglyceridemia-induced APIP was associated with a higher rate of severe acute pancreatitis (P = 0.025). Serum level of triglycerides showed a positive correlation with the severity of APIP (P = 0.039). The most frequent presentation of APIP was abdominal pain (93.7%, 30/32). There were no maternal or fetal deaths in our study. Apgar scores at 1 min, 5 min, and 10 min of the premature neonates was correlated with the severity of APIP of the mother (P = 0.022; 0.002; 0.002). CONCLUSION: High level of triglycerides may serve as a useful marker of the severity of APIP. The severity of APIP was associated with higher risk of neonate asphyxia. Appropriate timing of termination of pregnancy is a key imperative for APIP patients.

Conservative management versus cesarean hysterectomy in patients with placenta increta or percreta.

OBJECTIVE: To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta. MATERIALS AND METHODS: In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes. RESULTS: In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H, p<.001). There were more patients with blood loss >1000 ml in group H than in group C (93.6% [131/140] vs. 61.4% [86/140], p<.001). More patients received blood transfusions in group H than in group C (p=.014). There was no significant difference between the groups in terms of bladder injury, postoperative anemia, fever, and disseminated intravascular coagulation. Neonatal outcomes in the two groups were similar. CONCLUSION: Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Circular RNA ERBB2 Contributes to Proliferation and Migration of Airway Smooth Muscle Cells via miR-98-5p/IGF1R Signaling in Asthma.

BACKGROUND: Asthma belongs to chronic inflammatory respiratory diseases characterized by airway inflammation and remodeling. Circular RNAs (circRNAs) are promising therapeutic targets for various diseases, including asthma. In this work, we aim to investigate the role of circular RNA Erb-B2 receptor tyrosine kinase 2 (circERBB2) during progression of asthma. METHODS: Human airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to mimic cell remodeling. The expression of circERBB2, microRNA-98-5p (miR-98-5p), and insulin-like growth factor 1 receptor (IGF1R) was measured by qRT-PCR. Cell proliferation, migration and apoptosis were determined by cell counting-8 (CCK-8), transwell, and flow cytometry. Protein levels of PCNA, MMP-9, IGF1R were evaluated using Western blotting. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene experiment was adopted to evaluate the targeting relationship between miR-98-5p with circERBB2 and IGF1R. Interaction between RNAs was determined by RNA pulldown and RIP assay. RESULTS: The depletion of circERBB2 attenuated the proliferation, migration, and levels of inflammatory factors induced by PDGF-BB and cell apoptosis. CircERBB2 was identified to directly interact with miR-98-5p, and overexpression of miR-98-5p abolished the function of circERBB2 on PDGF-BB-stimulated ASMCs. IGF1R was identified as a target of miR-98-5p, and knockdown of IGF1R relieved the PDGF-BB-induced ASMCs proliferation and migration. CONCLUSION: Our work disclosed that knockdown of circERBB2 suppressed PDGF-BB-caused proliferation, migration and inflammatory response of ASMCs, through regulating miR-98-5p/IGF1R signaling, presented circERBB2 as a promising therapeutic target for asthma.

Disseminated intravascular coagulation associated organ failure in obstetric patients admitted to intensive care units: a multicenter study in China.

We aimed to determine disseminated intravascular coagulation (DIC)-associated organ failure and underlying diseases based on data from three ICU wards in tertiary hospitals in China from 2008 to 2016. The diagnosis of DIC was confirmed by an International Society of Thrombosis and Hemostasis score greater than or equal to 5. The maternal outcomes included the changes in organ function 24 h after ICU admission. The durations of hospital stay and ICU stay were recorded as secondary outcomes. Among 297 ICU admissions (median Sequential Organ Failure Assessment score, 4) for obstetric diseases, there were 87 DIC cases, with an estimated DIC incidence of 87 per 87,580 deliveries. Postpartum hemorrhage was the leading disease associated with DIC (71, 81.6%), followed by hypertensive disorders (27, 31.0%), sepsis (15, 17.2%), acute fatty liver of pregnancy (11, 12.6%) and amniotic fluid embolism (10, 11.5%). Compared with patients without DIC, those with DIC had higher rates of multiple organ dysfunction syndrome/death (27.6% vs 4.8%, p = 0.000), organ failure (36.8% vs 24.3%, p = 0.029), among which organ failure included acute renal failure (32.2% vs 10.0%, p = 0.000), respiratory failure (16.1% vs 8.6%, p = 0.057), disturbance of consciousness (12.6% vs 2.4%, p = 0.000) and DIC group also had higher rates of massive transfusion (52.9% vs 21.9%, p = 0.000), hysterectomy (32.2% vs 15.7%, p = 0.001), longer ICU (4 days vs 2 days, p = 0.000) and hospital stays (14 days vs 11 days, p = 0.005). DIC and amniotic fluid embolism were independent risk factors for organ failure in patients admitted to the ICU. Postpartum hemorrhage was the leading cause of DIC associated organ failure in obstetrics admitted to the ICU. The control of obstetric bleeding in a timely manner may improve obstetric prognoses.

A modified suture technique for the treatment of patients with pernicious placenta previa and placenta accreta spectrum: a case series.

BACKGROUND: Pernicious placenta previa complicated by placenta accreta spectrum (PAS) often leads to hysterectomy or even maternal death due to massive bleeding. In recent years, the application of balloons has received increasing attention. It is easier to use and has reasonably good effect. However, for some patients, especially those who still have some placental residue, there might still be active bleeding. To solve this problem, we propose a method of pressure sutures around the balloon to provide a better hemostasis effect. METHODS: An observational study was conducted on patients with pernicious placenta previa and PAS at the Beijing Chaoyang Hospital, Beijing, China, between January 2018 and January 2021. During surgery, an intrauterine balloon was used to compress the hemorrhage site, and two or more absorbable sutures were placed around the uterus to apply strong pressure on the balloon. This method is an updated modification of the Lu-suture which uses a Foley catheter balloon and only one suture. The main improvements include choosing different kinds of balloons depending on various conditions and the addition of a suture below the balloon to provide much stronger pressure and prevent the balloon slipping out through the dilated cervix. RESULTS: A total of 10 women underwent the procedure. The mean estimated intraoperative blood loss was 1,190±548 mL. Post-surgery, the blood loss was less than 200 mL in all patients. The mean blood transfusion [packed red blood cells (pRBC)] required was 2.2±2.6 units. The mean hemostatic time was 8.1±3.4 minutes. CONCLUSIONS: The modified suture technique provided an easy, cheap, and efficient surgical choice for patients with pernicious placenta previa and PAS.

Effect of comprehensive nursing on the appearance and recovery effect of oral squamous cell carcinoma patients.

OBJECTIVE: To investigate the effect of comprehensive nursing on the appearance and recovery of oral squamous cell carcinoma. METHODS: 52 patients with oral squamous cell carcinoma admitted to our hospital from February 2019 to February 2020 were selected and divided into a control group (n = 26, conventional nursing care) and an observation group (n = 26, comprehensive nursing). The postoperative hospital stay and postoperative intravenous infusion time, quality of life score, postoperative complications, nursing satisfaction, shape recovery, SAS score, etc. were compared between the two groups. RESULTS: (1) The observation group had a shorter postoperative hospital stay and postoperative intravenous infusion time compared to the control group. The observation group also showed higher scores of ADL, psychological function, physical function, and social function after nursing. Regarding the incidence of postoperative complications, the observation group was lower than the control group; the observation group had higher nursing satisfaction (92.31%) than the control group (61.54%) (All P < 0.05). (2) The satisfaction rate in terms of postoperative appearance recovery and overall recovery in the observation group were all significantly higher than the control group (P < 0.05). (3) The ASA score in observation group was significantly lower compared to the control group (inter-group effect: F = 76.210, P < 0.001), and the ASA score of both groups had a tendency to decrease with time (time effect: F = 36.580, P < 0.001); There is an interaction effect between grouping and time (interaction effect: F = 11.770, P < 0.001). (4) After nursing, the VAS score of the two groups of patients was lower than that before nursing, and the score of observation group patients was much lower (P < 0.05). CONCLUSION: The application of comprehensive nursing in patients with oral squamous cell carcinoma is remarkable, which can promote the recovery of patients' disease and their appearance, decrease postoperative complications, and relieve the anxiety feelings of patients, with a higher satisfaction rate.

MicroRNA-127-5p attenuates severe pneumonia via tumor necrosis factor receptor-associated factor 1.

Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1ß, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.

Reproductive outcomes of cesarean scar pregnancies pretreated with methotrexate and uterine artery embolization prior to curettage.

OBJECTIVE: To evaluate the reproductive outcomes of cesarean scar pregnancy (CSP) pretreated with methotrexate (MTX) and uterine artery embolization (UAE) prior to curettage. MATERIALS AND METHODS: The medical records of patients with CSP who were pretreated with MTX and UAE prior to curettage in our institute from January 2013 to December 2015 were collected and retrospectively reviewed. RESULTS: A total of 53 patients were eligible for further analysis. Consecutive systemic MTX or a single dose of MTX was administered in 31 or 15 patients, respectively. The UAE procedure was uneventful, and no side effects occurred. The duration of the curettage operation was 21.4 ± 10.4 min, and the volume of blood loss was 23.5 ± 61.6 ml. The serum ß-HCG level returned to normal 36.1 ± 10.1 days after the date of initial MTX administration. Eight of 10 patients with a desire to have children became pregnant naturally. Two (25%) patients developed recurrent CSP during the first trimester. One patient underwent emergency cesarean delivery and hysterectomy due to placental implantation and sudden massive hemorrhage during delivery. A total of 6 live newborns were delivered. CONCLUSION: Pretreatment with MTX and UAE prior to curettage is safe and effective for the management of CSP. The reproductive outcomes are encouraging.

The association between serum growth differentiation factor-15 and 3-month depression after acute ischemic stroke.

OBJECTIVE: The aim of this study was to assess the association between serum growth differentiation factor-15(GDF-15) and 3-month depression after acute ischemic stroke. METHODS: In this single-center prospective study, patients with first-ever acute ischemic stroke between March 2017 and November 2018 were included. Neurological and neuropsychological evaluations were conducted during the 3-month follow-up. The predictive value of GDF-15 to predict the post-stroke depression (PSD) within 3 months, was compared with other known predictors. RESULTS: The median level of GDF-15 in 310 stroke patients was 1285(IQR, 846-1934) ng/l. During the 3-month follow-up, 76 patients were defined as depression (24.5%; 95% confidence interval [CI]: 17.9%-29.3%), and GDF-15 levels in those patients were nearly more than 1 time greater as compared with patients who were free of depression (P < 0.001). Using the ROC curves, GDF-15 serum level at 1660 ng/l predicted the PSD with the highest sensitivity and specificity [67.1% and 77.4%, respectively; AUC=0.78, 95%CI: 0.72-0.84; P < 0.001]. Interestingly, When GDF-15 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.81(0.029) to 0.88(0.020). A significant difference in the AUC between the established risk factors alone and the addition of GDF-15 was observed (difference, 0.07[0.009]; P = 0.001). In a multivariate model using the elevated levels of GDF-15 (≥cut-off=1660 ng/l) vs. normal (

Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/ß-catenin and NF-κB signaling.

Morusin has been traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount of M. pneumoniae decreased by 24.6 ± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (P<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/ß-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/ß-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.

Cyanidin-3-O-glucoside promotes progesterone secretion by improving cells viability and mitochondrial function in cadmium-sulfate-damaged R2C cells.

Cadmium (Cd) is a poisonous metal that is toxic for male reproduction. Cyanidin-3-O-glucoside (C3G) as typical anthocyanin benefits many organs. In this study, we investigated the protective effects and associated underlying mechanisms of C3G against the toxicity of Cd on male reproduction in rat Leydig cell line R2C cells. Cells were pre-protected with C3G (5-160 µmol/L) for 2 h and then treated with cadmium sulfate (CdSO4) (10-160 µmol/L) for 24 h. The results showed that cytotoxicity, mitochondrial damage, superoxide dismutase 2 (SOD2), and overproduction of reactive oxygen species (ROS) in CdSO4-treated R2C cells were significantly reduced with C3G pre-treatment. Moreover, C3G pre-treatment led to upregulated expression of steroidogenic acute regulatory (StAR) protein and progesterone production. Our study suggests that C3G may be a potential therapeutic agent against Cd-induced reproductive toxicity.