Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype.

JOURNAL/nrgr/04.03/01300535-202419110-00029/figure1/v/2024-03-08T184507Z/r/image-tiff Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE-/- mice. However, little is known about the role of lnc_000048 in classically activated macrophage (M1) polarization. In this study, we established THP-1-derived testing state macrophages (M0), M1 macrophages, and alternately activated macrophages (M2). Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in macrophages. Flow cytometry was used to detect phenotypic proteins (CD11b, CD38, CD80). We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_000048. Flow cytometry, western blot, and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response, while over-expression of lnc_000048 led to the opposite effect. Western blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage polarization. Moreover, catRAPID prediction, RNA-pull down, and mass spectrometry were used to identify and screen the protein kinase RNA-activated (PKR), then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to PKR. Immunofluorescence (IF)-RNA fluorescence in situ hybridization (FISH) double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 macrophage. We speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation, leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor expression. Taken together, these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

Embolic stroke of undetermined source: Focusing on atrial cardiopathy and patent foramen ovale.

BACKGROUND: Atrial cardiopathy(AC) and patent foramen ovale (PFO) are two etiologies of embolic strokes of undetermined source (ESUS). We aimed to explore the relationship between them in ESUS. METHODS: A total of 1146 participants were included from January 2019 to June 2022, which included the ESUS group and non-embolic stroke which includes LAA(large arterial atherosclerosis) + SAO(small artery occlusion) group. AC was defined as the presence of at least one of the following: PTFV1(P-wave terminal force in lead V1) > 4000 µV*ms in the electrocardiograms, NT-proBNP(N-terminal probrain natriuretic peptide) > 250 pg/mL in laboratory tests or LAD(left atrial diameter) > 3.8 cm for women and > 4.0 cm for men in cardiac ultrasound. The presence of PFO was assessed by transthoracic echocardiography, transcranial Doppler ultrasound, transesophageal echocardiography or cardiac MRI. PFO was considered pathogenic if the RoPE score was 7 to 10. RESULTS: The prevalence of AC and PFO was higher in the ESUS group than the LAA + SAO group. The prevalence of AC was lower in ESUS patients with pathogenic PFO (37.9%) than those without PFO (68.4%) and with incidental PFO (64.0%) (p = 0.006). The prevalence of pathogenic PFO was lower in ESUS patients with AC than those without AC (6.0% vs. 17.8%, p = 0.006). The AUC(area under the curve) of PTFV1 for predicting ESUS was 0.724 [95%CI (0.686-0.762), p < 0.05)], indicating that PTFV1 the most valuable AC biomarker. CONCLUSIONS: The prevalence of AC is inversely related to the prevalence of pathogenic PFO in ESUS patients. PTFV1 was the most valuable index to predict ESUS among the AC biomarkers.

Metagenomic next-generation sequencing of bronchoalveolar lavage fluid in non-severe and severe pneumonia patients.

Metagenomic next-generation sequencing (mNGS) is widely used as a more promising technology than conventional tests. However, its clinical utility in the context of bronchoalveolar lavage fluid (BALF) samples for discriminating between non-severe and severe pneumonia is not well established. Thus, this study aimed to investigate the diagnostic performance of mNGS on BALF samples from 100 individuals suspected of pneumonia, and compared it with conventional microbiological tests (CMT) of BALF samples and the final clinical diagnosis. Twenty-seven cases of non-severe pneumonia and 73 cases of severe pneumonia patients were finally clinically diagnosed. Among 100 cases, diagnostic performance of mNGS and culture showed a significant difference; 65 cases had the same sample types, of which 25 cases were diagnosed as positive by mNGS only (38.46%) and 1 was diagnosed as positive by culture only (1.54%). Moreover, 24 cases were diagnosed positive in both mNGS and culture (36.92%) and 15 cases tested negative in both mNGS and culture (23.08%). Among 35 cases, 28 out of 35 cases were diagnosed as positive by mNGS, while only 4 out of 35 cases were diagnosed as positive by the indirect immunofluorescence method (IIFT). In addition, the positive rate of mNGS was higher than that of culture in cases regardless of prior antibiotic exposure. Mixed pathogens were found to be significantly more prevalent in severe pneumonia patients than in non-severe pneumonia patients. Importantly, among 38 cases who were diagnosed solely by mNGS, 25 patients experienced an improved outcome after physicians changed the therapy according to the mNGS results. In conclusion, the results showed that mNGS of BALF represents a potentially effective tool for detection of mixed pathogens in severe pneumonia.

Interactive effect between sleep and exercise on depressive symptoms in Chinese adolescents.

Objectives: The study aimed to investigate the effects of sleep and exercise, individually and jointly, on depressive symptoms in Chinese adolescents. Methods: Cluster sampling was used to conduct a cross-sectional, electronic survey among 11,563 students from five primary and high schools in Sichuan Province in Western China. The questionnaire contained custom-designed items concerning sleep and exercise, while it used the Center for Epidemiologic Studies Depression Scale to assess depressive symptoms and the Core Self-Evaluations Scale to assess core self-evaluation. Data were analyzed using descriptive statistics and multivariate linear regression. Results: A total of 10,185 valid questionnaires were collected, corresponding to an effective response rate of 88.1%. Among the respondents in the final analysis, 5,555 (54.5%) were boys and 4,630 (45.5%) were girls, and the average age was 15.20 ± 1.72 years (range, 11-18 years). Only less than half of the respondents (4,914, 48.2%) reported insufficient sleep, while the remainder (5,271, 51.8%) had adequate sleep. Nearly one-quarter (2,250, 22.1%) reported insufficient exercise, while the remainder (7,935, 77.9%) reported adequate exercise. More than half of the respondents (5,681, 55.7%) were from vocational high school, 3,368 (33.1%) were from junior high school, 945 (9.3%) were from senior high school, and 191 (1.9%) were from primary school. The prevalence of depressive symptoms among all respondents was 29.5% (95% CI 28.7%-30.4%). When other variables were controlled, the depression score did not vary significantly with gender (B = -0.244, SE = 0.127, P = 0.054), but it decreased by 0.194 points per 1-year increase in age (B = -0.194, SE = 0.037, P < 0.001). Students getting adequate sleep had depression scores 2.614 points lower than those getting insufficient sleep (B = -2.614, SE = 0.577, P < 0.001), while students who engaged in adequate exercise had depression scores 1.779 points lower than those not exercising enough (B = -1.779, SE = 0.461, P < 0.001). The depression score decreased by 0.919 points per 1-point increase in the core self-evaluation score (B = -0.919, SE = 0.008, P < 0.001). In regression controlling for gender, age, and core self-evaluation, sleep and exercise were found to be related significantly to influence depressive symptoms (B = 0.821, SE = 0.315, P = 0.009). Conclusion: Adequate sleep and adequate exercise are individually associated with milder depressive symptoms in Chinese adolescents. Our results further highlight the need for researchers and clinicians to take into account not only the individual but also the joint effects of sleep and exercise on depression in adolescents when conducting research and designing interventions. If sleep or physical exercise has substantially reduced the risk of depressive symptoms, further reductions by improving sleep and exercise become difficult and may even have opposite effects.

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer: A Phase 3 Randomized Clinical Trial.

Importance: The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. Objective: To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Interventions: Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/µL [to convert to ×109/µL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. Main Outcomes and Measurements: The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. Results: A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. Conclusion and Relevance: This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. Trial Registration: ClinicalTrials.gov Identifier: NCT03709316.

Activity-to-sedentary ratio provides novel insight into mortality reduction among male survivors of cardiovascular disease in the United States: national health and nutrition examination survey, 2007-2014.

BACKGROUND: Lower physical activity and sedentary behavior have been identified as modifiable risk factors for cardiovascular disease (CVD). However, the quantitative, dose-response association between activity-to-sedentary ratio (ASR) and mortality is unknown. METHODS: Prospective cohort studies with participants 50 to 80 years that reported the association between recreational physical activity, sedentary behavior, and all-cause mortality were included from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) and followed through December 31, 2015. Cox or Weibull regression models and restricted cubic splines were used to determine the association between ASR and all-cause mortality. RESULTS: Sixty deaths occurred among 498 CVD survivors, with a median of 56 months of follow-up. After accounting for all covariates, CVD survivors with an ASR between 0.21 and 0.57 (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and those with an ASR more than 0.57 (HR, 0.40; 95% CI, 0.20-0.81) were at significantly lower risk for mortality than participants with an ASR <  0.21. Moreover, a nonlinear negative association and an L-shaped association were observed for the level of ASR with risk of mortality among CVD survivors (P for nonlinearity = 0.004). What's more, adjusting for covariates, a statistically significant interaction (P for interaction = 0.016) between sex and ASR, an increase of ASR more than and equal to 0.18 was associated with a lower risk of mortality among males (HR, 0.23; 95% CI, 0.12-0.46). CONCLUSIONS: An negative correlation between ASR and mortality in CVD survivors, especially in males when ASR is more than 0.18. Our novel findings provide further insights into easing the global burden of deaths.

Development of a nomogram for predicting pelvic lymph node metastasis in cervical squamous cell carcinoma.

OBJECTIVE: To develop and validate a nomogram for predicting pelvic lymph node metastasis (LNM) in cervical squamous cell carcinoma (SCC). METHODS: This was a retrospective study that included 715 patients with cervical SCC who underwent radical hysterectomy and bilateral pelvic lymphadenectomy between 2009 and 2018. Logistic regression analysis was used to identify independent risk factors for pelvic LNM. Based on these risk factors, a nomogram predicting LNM risk was constructed and internally validated using the bootstrapping resampling method. RESULTS: The rate of LNM in FIGO (the International Federation of Gynecology & Obstetrics) Stage IA2-IIA2 cervical SCC was 24.2%. In multivariate analysis, FIGO Stage II, moderately differentiated or poorly differentiated histology, abnormally elevated serum SCC-antigen, and triglyceride were identified as independent risk factors for LNM. Tumor size greater than 2 cm and parametrial involvement had borderline significance. Ultimately, the nomogram contained the six variables mentioned above, showing positive calibration and positive discrimination. The area under the receiver operating characteristic curvewas 0.827 and the bootstrap-validated C-index was 0.827. The Youden index of this paper was 0.540. CONCLUSIONS: We developed and validated a nomogram to predict pelvic LNM in SCC based on clinical data, which can help physicians develop an optimal treatment strategy.

Serum adenosine deaminase activity and acute cerebral infarction: a retrospective case-control study based on 7913 participants.

BACKGROUND: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear. METHODS: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. RESULTS: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect. CONCLUSIONS: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.

Compromised cerebrovascular reactivity in migraineurs with right-to-left shunts: a potential mechanism of white matter hyperintensities.

OBJECTIVE: Our study aims to explore the changes of cerebrovascular reactivity (CVR) in migraineurs with right-to-left shunts (RLS), and further evaluate the association between CVR and the occurrence of the white matter hyperintensities (WMHs). METHODS: RLS was diagnosed based on a contrast enhancement transcranial Doppler (c-TCD) examination. The breath holding index (BHI), which represents CVR, was measured from the middle cerebral artery (MCA) using a TCD with the breath-holding method. WMHs was defined as clearly hyperintense areas in 3 T magnetic resonance imaging (MRI). All migraineurs underwent a standardized questionnaire for family and personal history and detailed migraine features. RESULTS: Three hundred and ninety-seven migraineurs and 100 controls were included in our study. The BHI was significantly lower in migraineurs than controls (0.527 ± 0.709 vs. 0.674 ± 0.489, P = 0.016). Moreover, migraineurs with RLS had lower BHI than those without RLS (0.504 ± 0.671 vs. 0.674 ± 0.721, p = 0.024). Migraineurs with WMHs had lower BHI than those without (0.47 ± 0.71 vs. 0.75 ± 0.49, p = 0.035). The reduced BHI was an independent influencing factor for WMHs in our study (OR = 0.338; 95% CI = 0.142-0.806, p = 0.014). CONCLUSION: Our results indicated that BHI was reduced in migraineurs, and the reduced BHI was associated with RLS. Moreover, the reduced CVR in migraineurs with RLS might be related to the occurrence of WMHs.

Core self-evaluation as mediator between depressive symptoms and suicidal ideation in adolescents.

OBJECTIVES: To explore the role of core self-evaluation in mediating between depressive symptoms and suicidal ideation in Chinese adolescents. METHODS: We used the cluster sampling method to analyze 11,563 students from five primary and secondary schools in China for depressive symptoms, core self-evaluation, and suicidal ideation using the following scoring scales: Core Self-Evaluation Scale (CSES), Center for Epidemiologic Survey Depression Scale (CES-D), the Second Edition of the Beck Depression Inventory (BDI- II), Screen for Child Anxiety Related Emotional Disorders (SCARED), and Adolescent Self-Rating Life Events Checklist (ASLEC). RESULTS: The incidence of depression was 29.7%; anxiety, 34.2%; and suicidal ideation, 28.0%. Core self-evaluation was a protective factor for suicidal ideation [OR 0.947, 95% CI 0.937-0.959, p<0.001]. Conversely, depression as measured by the CSES score was a risk factor for suicidal ideation (OR 1.084, 95% CI 1.073-1.096, p<0.001), as were anxiety as measured by the SCARED score (OR 1.011, 95% CI 1.006-1.016, p<0.001) and adolescent life events according to ASLEC score groups (OR 1.524, 95% CI 1.434-1.621, p<0.001). Core self-evaluation mediated the relationship between depression and suicidal ideation with an effect size of 13.9%. CONCLUSIONS: Better core self-evaluation is a protective factor against suicidal ideation and mediates the relationship between depression and suicidal ideation. We may be able to reduce the risk of suicidal ideation and therefore suicide among adolescents by improving their core self-evaluation.

Lower uric acid level may be associated with hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND: Previous studies have shown that uric acid (UA) is a powerful water-soluble antioxidant and free radical scavenger for humans. However, the relationship between serum uric acid (SUA) and hemorrhagic transformation (HT) is still controversial. To address this challenge, we aimed to explore the association between serum UA and HT in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). METHODS: A retrospective analysis was conducted in patients with anterior circulation AIS who underwent IVT at Affiliated Hospital of Qingdao University from 2016 to 2021. HT was evaluated by CT or MRI within 7 days after admission. Baseline demographic, clinical, and laboratory data were compared between the HT and non-HT groups, and between different types of HT groups which were documented according to the European Cooperative Acute Stroke Study III Classification (ECASS III). RESULTS: A total of 727 AIS patients were enrolled, including 112 patients who experienced HT (HT group) and 615 patients who did not experience HT (non-HT group). Patients with HT had significantly lower UA levels compared to those without HT (253.65 ± 97.75 vs 315.97 ± 96.42, p < 0.001); however, there was no significant difference for UA levels in different types of HT (p = 0.907). After adjusting confounders, patients in the fourth UA quartile showed a significant decrease in HT compared with those in the first quartile (OR 0.266, 95% CI 0.107-0.661, p = 0.006). The best cutoff value was identified as 218.5 µmol/L after analysis. CONCLUSIONS: These findings suggest that low levels of UA may be associated with HT after IVT.

The Combined Regulation of Long Non-coding RNA and RNA-Binding Proteins in Atherosclerosis.

Atherosclerosis is a complex disease closely related to the function of endothelial cells (ECs), monocytes/macrophages, and vascular smooth muscle cells (VSMCs). Despite a good understanding of the pathogenesis of atherosclerosis, the underlying molecular mechanisms are still only poorly understood. Therefore, atherosclerosis continues to be an important clinical issue worthy of further research. Recent evidence has shown that long non-coding RNAs (lncRNAs) and RNA-binding proteins (RBPs) can serve as important regulators of cellular function in atherosclerosis. Besides, several studies have shown that lncRNAs are partly dependent on the specific interaction with RBPs to exert their function. This review summarizes the important contributions of lncRNAs and RBPs in atherosclerosis and provides novel and comprehensible interaction models of lncRNAs and RBPs.

Plaque Length Predicts the Incidence of Microembolic Signals in Acute Anterior Circulation Stroke.

Microembolic signals (MES) of the carotid artery are associated with plaque destabilization and reoccurrence of stroke. Previous studies have focused primarily on the degree of carotid artery stenosis and plaque components, and the relationship between plaque length and microembolic sign has received little attention. We aimed to find the association between carotid plaque length (CPL) and the presence of MES. We conducted a retrospective observational cross-sectional study. A total of 84 acute anterior-circulation ischemic stroke/transient ischemic attack (TIA) patients with carotid artery atherosclerosis were classified into an MES-positive (MES+) group and MES-negative (MES-) group. We measured multiple parameters of carotid plaque size (length, thickness) in each patient and evaluated the relationship between different plaque parameters and occurrence of MES. We found that male, carotid artery stenosis (CAS), CPL, carotid plaque thickness (CPT), and intima-media thickness (IMT) of the carotid artery were each significantly different between two groups (all P < 0.05). The multivariate analysis showed CPL (odds ratio (OR), 1.109; 95% CI, 1.044-1.177; P = 0.001) to be independently associated with the presence of MES. The areas under the ROC curves (AUCs) for CPL for predicting MES were 0.777 (95% CI, 0.640-0.914; P < 0.001). The cutoff value of CPL for predicting MES was 16.7 mm, with a sensitivity of 88.2% and a specificity of 77.6%. We found that CPL was a meaningful independent predictor of MES. Therefore, CPL may be useful for risk stratification of long and nonstenotic plaques in anterior circulation stroke.

Laparoscopic Radical Hysterectomy Results in Higher Recurrence Rate Versus Open Abdominal Surgery for Stage IB1 Cervical Cancer Patients With Tumor Size Less Than 2 Centimeter: A Retrospective Propensity Score-Matched Study.

OBJECTIVE: To compare the oncologic outcomes between laparoscopic and open radical hysterectomy in patients with stage IB1 cervical cancer lesion less than 2 cm. METHODS: Patients diagnosed FIGO (2009) stage IB1 (tumor diameter <2 cm) and underwent radical hysterectomy in our hospital between March 2008 and November 2018 were studied. A propensity-matched comparison (1:2) was conducted to minimize selection biases. Demographic and baseline oncologic characteristics were balanced between groups. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier model, along with univariable and multivariable regression analysis. RESULTS: A total of 261 patients were enrolled in this study after propensity-matching, with 174 in the open group and 87 in the laparoscopic group. Disease relapsed in seven patients in laparoscopy group, and the recurrence rate was 8.0% (7/87). There were eight patients underwent abdominal radical hysterectomy experienced recurrence, and the recurrence rate was 4.6% (8/174). The multivariate analysis model revealed that laparoscopic operation was associated with higher risk of recurrence than abdominal radical hysterectomy (HR, 3.789; 95% CI, 1.143-12.559; p = 0.029). There were five patients or 2.9% (5/174) died in open surgery group and the corresponding percentage in laparoscopy group was 2.3% (2/87). No difference was found in OS between the two groups (HR, 1.823; 95% CI, 0.2673-12.44; log-rank p = 0.5398). All the recurrence occurred within two years after operation in the laparoscopy group, among which pelvic recurrence (85.7%) was dominant. CONCLUSION: Traditional laparotomy radical hysterectomy has a lower recurrence rate when compared with laparoscopic operation in those cervical cancer patients with a foci diameter less than 2 cm. However, no detrimental effect on survival was found in minimal invasive operation group. Further multi-center prospective trials are needed to confirm our results on a large scale.

Prognostic significance of poorly differentiated histology and impact of adjuvant chemotherapy in early squamous cell carcinoma of cervix uteri.

OBJECTIVE: This study is to determine whether the addition of cisplatin-based chemotherapy after radical hysterectomy will improve the survival of low-risk squamous cervical carcinoma with poor differentiation. METHODS: Patients with low-risk squamous cervical cancer (FIGO IA2-IIA, absent high- and intermediate-risk factors after pathological evaluation) were eligible for this study. As first, the prognostic relevance of G3 versus G1/G2 among patients with low-risk squamous cervical cancer was analyzed, then, the oncological results of postoperative chemotherapy among low-risk squamous cervical cancer with poor differentiation was explored. RESULTS: Totally, there were 367 low-risk squamous cervical cancer patients, of whom 161 were poor-differentiated (47 in the chemotherapy group and 114 in the nonchemotherapy group), with a median follow-up time of 56 months. Patients with G3 displayed a significantly worse overall survival (p = 0.035), and a higher recurrence rate (p = 0.014) than patients with G1/G2. Compared with the nonchemotherapy group, the hazard ratios (95%CI) for recurrence-free survival in the chemotherapy group was 0.24 (0.06-0.93), (p = 0.038). No difference in overall survival was observed between the chemotherapy group and the nonchemotherapy group. CONCLUSIONS: The addition of cisplatin-based chemotherapy following surgery significantly improved recurrence-free survival for low-risk, poor differentiation, and early stage squamous cervical cancer patients.

Management of pelvic organ prolapse of ruptured and extruded bladder from a rare complication of vaginal hysterectomy: a case presentation.

BACKGROUND: The prolapse of a ruptured and extruded bladder after vaginal hysterectomy is rare in clinical practice. We report the case of a significant mass that prolapsed from the vagina after a vaginal hysterectomy in a multiparous postmenopausal woman. CASE PRESENTATION: A 67-year old multiparous postmenopausal Chinese woman was found to have a significant mass extruding from the vagina after a vaginal hysterectomy. The mass was a ruptured and everted bladder, and the diagnosis was confirmed after physical and imaging examinations and urethral catheterization. The patient underwent an emergency operation for mass reduction, bladder repair, and partial colpocleisis under general anesthesia. She recovered without prolapse or urinary drainage complications after 35 months of follow-up. CONCLUSIONS: The present case serves as a guide for the management of patients with pelvic organ prolapse. The condition of patients should be carefully evaluated before surgery, and individualized operation should be performed. Careful postoperative follow-up is crucial for the timely exclusion of complications, especially in elderly patients with persistently increased abdominal pressure.

Clinicalpathologic and Prognostic Significance of CGI-58 in Endometrial Cancer.

Recent studies have reported that CGI-58 played an important role in carcinogenesis and tumoral progression in several cancers. In this study, we investigated the expression and prognostic value of CGI-58 in patients with endometrail cancer. Initially, the expression of CGI-58 was analyzed in 552 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Then, the mRNA level of CGI-58 from 32 normal endometrium and 40 endometrial cancer tissues was determined using real-time PCR. In addition, immunohistochemical staining of CGI-58 was performed in 140 endometrial specimens including 35 normal endometrial tissues, 25 atypical endometrial hyperplasia and 80 endometrial cancers. The expression of CGI-58 was significantly up-regulated in endometrial cancer tissues compared with normal endometrial tissue both in TCGA database and clinical cohorts. Over-expression of CGI-58 was significantly correlated with poor histological differentiation. Furthermore, high levels of CGI-58 expression were significantly associated with shorter overall survival for all analyzed cases. Our findings demonstrate that CGI-58 is up-regulated in endometrial cancer and high CGI-58 expression is a poor prognostic marker for endometrial cancer. CGI-58 may be a potential contributor to endometrial cancer oncogenesis and progression.

The Gas Content Characteristics of Nanopores Developed in a Normal Pressure Shale Gas Reservoir in Southeast Chongqing, Sichuan Basin, China.

To evaluate the gas content characteristics of nanopores developed in a normal pressure shale gas reservoir, the Py1 well in southeast Chongqing was selected as a case study. A series of experiments was performed to analyze the total organic carbon content, porosity and gas content using core material samples of the Longmaxi Shale from the Py1 well. The results show that the adsorbed gas and free gas content in the nanopores developed in the Py1 well in the normal pressure shale gas reservoir range from 0.46-2.24 m3/t and 0.27-0.83 m3/t, with average values of 1.38 m3/t and 0.50 m3/t, respectively. The adsorbed gas is dominant in the shale gas reservoir, accounting for 53.05-88.23% of the total gas with an average value of 71.43%. The Gas Research Institute (GRI) porosity and adsorbed gas content increase with increasing total organic carbon content. The adsorbed gas and free gas contents both increase with increasing porosity value, and the rate of increase in the adsorbed gas content with porosity is larger than that of free gas. Compared with the other five shale reservoirs in America, the Lower Silurian Longmaxi Shale in the Py1 well developed nanopores but without overpressure, which is not favorable for shale gas enrichment.

Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424-5p/suppressor of zeste 12 pathway.

Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424-5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424-5p locus. Furthermore, miR-424-5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424-5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424-5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.

Hesperetin ameliorates lipopolysaccharide-induced acute lung injury via the miR-410/SOX18 axis.

Hesperetin (Hesp), a dihydroflavone, has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and antitumor effects, as well as cardiovascular protection. It also has protective effects against acute lung injury (ALI); however, the exact mechanism remains unclear. In the present study, the protective effects and mechanism of Hesp in the lungs were investigated. Hematoxylin and eosin staining was used to examine pathological changes in the lungs. Enzyme-linked immunosorbent assay was used to detect proinflammatory cytokine levels. In addition, reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to observe the transcription and translation changes in the related genes, respectively. The results indicate that Hesp not only improves histopathological changes in the lungs but decreases the wet/dry ratio. In addition, total cell counts and the number of neutrophils and macrophages were lower in the bronchoalveolar fluid after Hesp treatment, consistent with the change in proinflammatory cytokine levels. MicroRNA-410 (miR-410) levels were significantly lower in the lung tissues of ALI mice and were reversed after Hesp treatment. Furthermore, miR-410 overexpression due to injection with agomiR-410 produced similar protective effects as Hesp. However, blocking miR-410 inhibited the protective effects of Hesp in the lungs of ALI mice. In addition, miR-410 has been shown to target the inhibition of sex determining region Y-box 18 (SOX18), indicating that Hesp might alleviate inflammatory secretion by blocking the miR-410/SOX18 axis. Thus, Hesp might be a potential agent for the treatment of ALI.