The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Small extracellular vesicles facilitate epithelial-mesenchymal transition in chronic rhinosinusitis with nasal polyps via the miR-375-3p/QKI axis.

BACKGROUND: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated. METHODS: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments. RESULTS: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375- 3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3'-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity. CONCLUSIONS: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

[New 2023 global definition of acute respiratory distress syndrome: progress and limitation].

Acute respiratory distress syndrome (ARDS) presents a challenge in clinical diagnosis as it lacks a definitive gold standard. Over the past 55 years, there have been several revisions to the definition of ARDS. With the progress of clinical practice and scientific research, the limitations of the "Berlin definition" have become increasingly evident. In response to these changes, the 2023 global definition of ARDS aims to address these issues by expanding the diagnostic targets, chest imaging, and methods for assessing hypoxia. Additionally, the new definition increases the diagnostic criteria to accommodate resource-constrained settings. The expansion facilitates early identification and treatment interventions for ARDS, thereby advancing epidemiological and clinically related research. Nevertheless, the broad nature of this revision may include patients who do not actually have ARDS, thus raising the risk of false-positive diagnoses. Therefore, additional verification is crucial to ascertain the validity and accuracy of the 2023 global definition of ARDS.

[Investigation of the effects and mechanisms of berberine on a mouse model of polycystic ovary syndrome: based on intestinal flora analysis].

Objective: To examine the impact of berberine on polycystic ovary syndrome (PCOS) in mice, and to investigate the effects of berberine on the intestinal flora and the intestinal flora on PCOS. Methods: A mouse model of PCOS was established by administering dehydroepiandrosterone in combination with high fat diet, and the mouse model was given a berberine treatment. The study consisted of a blank control group (C group), a PCOS model group (M group) and a berberine treatment group (T group). During the experiment, the mice were closely monitored through timed body weight measurements and estrous cycle monitoring; intraperitoneal glucose tolerance test and insulin tolerance test were done. Upon completion of the pharmacological intervention, the wet weights of liver, ovary and fat deposits of mice were assessed and subjected to HE staining to confirm the success of PCOS modeling and the efficacy of berberine. Additionally, fecal samples were analyzed for intestinal flora through 16S rRNA analysis. Results: The PCOS model was established successfully, berberine alleviated the disturbance of estrous cycle in mice, and significantly alleviated fat accumulation and metabolic abnormalities of glucose in mice. The cross-sectional area of fat pad cells in T group was (2 858±146) µm², which was significantly lower than that in M group [(9 518±347) µm²], and the difference was statistically significant (P<0.001). The blood glucose levels in T group were significantly lower than those in M group (P<0.05). The composition and structure of intestinal flora in mice of M group with PCOS (compared with C group) and in mice of T group after berberine intervention (compared with M group) were significantly altered. However, alpha diversity did not change significantly among three groups (P>0.05). Conclusion: Berberine could alleviate PCOS by intervening in the alterations of gut microbiota.

[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Successful Eisenmenger syndrome-targeted drug therapy in pregnant women: a case series and literature review.

OBJECTIVE: To clarify the real-world outcomes in pregnant women with Eisenmenger syndrome (ES) in the new therapeutic era and provide a literature review. DESIGN: Retrospective case and literature review. SETTING: Tertiary referral hospital (The Second Xiangya Hospital of Central South University). SAMPLE: Thirteen women with ES delivered between 2011 and 2021. METHODS: Respective study and literature reviews. MAIN OUTCOMES MEASURES: Maternal and neonatal mortality and morbidity. RESULTS: 12/13 (92%) pregnant women were treated with targeted drugs. 9/13 (69%) of patients had heart failure, but no maternal deaths occurred. 12/13 (92%) of women chose caesarean delivery. One pregnant woman gave birth at 37+1  weeks, and the remaining 12 (92%) patients had preterm birth. 10/13 (77%) women gave birth to live infants, of which 9/10 (90%) were low birthweight infants with a mean birthweight of 1575 g. The infant mortality rate was 1/10 (10%). Cardiac functional class improved during pregnancy, probably due to therapy; 11/13 (85%) of the pregnant women were in cardiac functional level III/IV at admission and 12 (92%) were in cardiac functional class II/III at discharge. Our literature review identified 72 cases of pregnancy with ES from 11 studies, which were characterised by a low rate of targeted drug use (28%) and a high maternal mortality rate of 24% in the perinatal period. CONCLUSION: Our case series and literature review suggest that targeted drugs may be key to improving maternal mortality in ES.

[Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis].

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

[Development and validation of a prognostic prediction model for patients with stage â to â ¢ colon cancer incorporating high-risk pathological features].

Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.

[Evaluation and clinical significance of gas exchange in patients with acute respiratory distress syndrome].

Gas exchange abnormalities is the pathophysiology characteristic of acute respiratory distress syndrome (ARDS). The severity of gas exchange abnormalities not only reflect the severity and outcome of the disease, but could also be an important index to guide individual mechanical ventilation settings and evaluate the therapeutic effects of inhaled vasodilator. The common techniques to measure gas exchange include multiple inert gas elimination technique, automatic lung parameter estimator, electrical impedance tomography, and single-photon emission CT. Nowadays, bedside techniques and measurements for improving gas exchange function in ARDS patients are still limited. Therefore, the improvement and promotion of bedside real-time gas exchange monitoring technology may achieve the goal of personalized medicine in ARDS. This article reviewed the common evaluation methods of gas exchange function in ARDS and their significance, in order to pay more attention to the evaluation of gas exchange function and further improve the prognosis of patients with ARDS.

[Effects of one-stop hybrid operation on the risk and prognosis of brain arteriovenous malformations with posterior feeding artery].

Objective: To explore the effect of the combination of posterior circulation embolization and micro-resection on the risk and prognosis in patients with brain arteriovenous malformations (bAVMs) supplied by posterior circulation in a one-stop hybrid operation setting. Methods: Patients with bAVMs supplied by posterior circulation who received surgical treatment in Beijing Tiantan Hospital, Capital Medical University, were enrolled from January 2016 to December 2019 from a prospective, multicentral cohort (NCT03209804). The patients were divided into the posterior circulation embolization group and the non-posterior circulation embolization group. Propensity score matching (PSM) (1∶1) was performed according to the baseline information, the morphology of bAVMs, vascular architecture, and Spetzler-Martin grade of brain lesions. The primary endpoint was the deterioration of neurological function. The secondary endpoints were perioperative complications. The differences in surgical risk and clinical prognosis between the two groups were compared. Results: Five hundred and forty-five patients were enrolled in the cohort, and 38.3% met the included criteria (n=209 cases), with 42 cases in the posterior circulation embolization group and 167 cases in the non-posterior circulation embolization group. Depending on whether the patients were posterior circulation embolized, 39 patients in the posterior circulation embolization group and 39 patients in the non-posterior circulation embolization group were finally included after performing PSM. There were 50 males and 28 females, aged 5-58 (30±13) years. The exacerbation rate of neurological dysfunction in the posterior circulation embolization group was higher than that in the non-posterior circulation embolization group three months after surgery, however there was no statistically significant difference between the two groups [15.4% (6/39) vs 2.6% (1/39), P=0.107]. The intraoperative blood loss in the embolization group was significantly less than that in the non-embolization group [650 (500, 1 500) ml vs 1 200 (800, 2 000) ml, P=0.002]. There was no significant difference in microsurgery time between the two groups [437 (374, 521) min vs 424 (359, 601) min, P=0.865]. Likewise, there were no statistically significant differences in the incidence of postoperative complications and aggravation of neurological dysfunction, including postoperative bAVMs residual [5.1%(2/39) vs 7.7%(3/39), P=1.000], hemorrhagic complications [5.1%(2/39) vs 0(0), P=0.494], postoperative ischemic complications [10.3%(4/39) vs 5.1%(2/39), P=0.675], neurological dysfunction at discharge (17.9% vs 15.4%, P=0.755), and one-year neurological dysfunction [5.1%(2/39) vs 2.6%(1/39), P=1.000]. Conclusions: Posterior circulation embolization of bAVMs in a one-stop hybrid operation can effectively reduce intraoperative bleeding and surgical risk. Embolization of the feeding artery has no significant impact on the perioperative complications and neurological outcomes.

[Analysis of prognosis factors of postoperative cardiac complications in colorectal cancer patients with comorbid coronary artery disease].

Objective: To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease. Methods: Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results: After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years(OR=3.195, 95%CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes (OR=2.551, 95%CI: 1.294 to 5.025, P=0.007), emergency surgery (OR=4.717, 95%CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio (OR=1.114, 95%CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions: Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

A prospective study of health related quality of life, bowel and sexual function after TaTME and conventional laparoscopic TME for mid and low rectal cancer.

BACKGROUND: The aim of our study was to evaluate short -term (3 months) and medium-term (12 months) postoperative effects on health related quality of life (HRQoL), bowel and sexual function after transanal total mesorectal excision (TaTME)  in comparison with conventional laparoscopic total mesorectal excision (TME). METHODS: A prospective study was conducted on consecutive patients who had conventional laparoscopic TME and TaTME at our institution from November 2014 to December 2018.We evaluated HRQoL and bowel function using validated scales including the European Organization for Research and Treatment of Cancer Quality of Life of colorectal cancer specific module (EORTC-QLQ-CR29), International Index of Erectile Function (IIEF-5), Female Sexual Function Index (FSFI), low anterior resection syndrome (LARS) score and Wexner score. Patients were matched one-to-one through propensity score matching. Outcomes of the questionnaires at 3 and 12 months were compared. RESULTS: Sixty patients were enrolled in the study. There were 30 in the conventional laparoscopic group (13 males; median age 69.3 years [range 35-80 years]) and 30 in the TaTME group (14 males; median age 75.6 years [range 42-83 years]). Three months after ileostmy closure, patients in the TaTME group had significantly more buttock pain (p = 0.030), bloating (p = 0.023), stool frequency (p = 0.013), flatulence (p < 0.001) and fecal incontinence (p = 0.044), although none of these differences persisted at 12 months. Patients in the TaTME group had a higher median overall LARS score at 3 months (p = 0.032) but there was no difference at 12 months. At 12 months after TaTME female patients had better women's sexual interest (p = 0.039) and dyspareunia scores (p < 0.001), while male patients had better erectile function (p = 0.038). Other scales did not reveal a significant difference at either 3 of 12 months between groups. CONCLUSIONS: Compared with patients with mid and low rectal cancer treated with conventional laparoscopic TME, those treated with TaTME have worse HRQoL and bowel function for a short period after primary resection, but seem to have better sexual function in the long term.

[The effects of positive end-expiratory pressure on central venous pressure in patients with different chest wall elastic resistance].

Objective: To investigate the role of chest wall elastic resistance in determining the effects of positive end-expiratory pressure (PEEP) on central venous pressure (CVP) in patients with mechanical ventilation (MV). Methods: In this prospective study, according to the median of ratio of chest wall elastic resistance to respiratory system elastic resistance (Ers), patients were divided into high chest wall elastic resistance group (Ecw/Ers≥0.24) and low chest wall elastic resistance group [elastance of chest wall (Ecw)/Ers<0.24]. PEEP was set at 5, 10, 15 cmH2O (1 cmH2O=0.098 kPa) respectively. Clinical data including CVP, heart rate (HR), blood pressure (BP) and respiratory mechanics were recorded. Results: Seventy patients receiving MV were included from November 2017 to December 2018. Clinical characteristics including age, BP, HR, baseline PEEP, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F) and comorbidities were comparable in two groups. However, patients with high Ecw/Ers ratio presented higher body mass index (BMI) than those with low Ecw/Ers ratio[ (25.4±3.2) kg/m2 vs. (23.4±3.2) kg/m2, P=0.011]. As PEEP increased from 5 cmH2O to 10 cmH2O, CVP in high Ecw/Ers group increased significantly compared with that in low Ecw/Ers group [1.75(1.00, 2.13) mmHg (1 mmHg=0.133kPa) vs. 1.50(0.50, 2.00)mmHg,P=0.038], which was the same as PEEP increased from 10 cmH2O to 15 cmH2O [2.00(1.50, 3.00)mmHg vs. 1.50(1.00, 2.00)mmHg,P=0.041] or PEEP increased from 5 cmH2O to 15 cmH2O [ 3.75(3.00,4.63)mmHg vs. 3.00(1.63, 4.00)mmHg, P=0.012]. When PEEP increased from 5 cmH2O to 10 cmH2O, 10 cmH2O to 15 cmH2O and 10 cmH2O to 15 cmH2O, there were significant correlations between Ecw/Ers and CVP elevation (r=0.29, P=0.016; r=0.31, P=0.011; r=0.31, P=0.01 respectively). Conclusions: In patients receiving mechanical ventilation, elevation of PEEP leads to a synchronous change of CVP, which is corelated with patients' chest wall elastic resistances.

[The safety and efficacy of Firesorb bioresorbable scaffold in first-in-man study for coronary artery disease: the four-year outcomes].

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.

Exposure to risperidone versus other antipsychotics and risk of osteoporosis-related fractures: a population-based study.

OBJECTIVE: Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. METHODS: Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. CONCLUSION: Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.

The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells.

Lung cancer is one of the leading causes of death worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer. Long noncoding RNAs (lncRNAs) are closely associated with the development and progression of various cancers, including lung cancer. The purpose of this study was to explore the potential role and molecular mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating the proliferation, apoptosis, migration, and invasion of NSCLC cells. The expressions of PVT1, integrin ß-8 (ITGB8), and miR-145-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of ITGB8, MEK, p-MEK, ERK, and p-ERK were measured by western blot analysis. Cell proliferation, apoptosis, migration, and invasion were determined by MTT assay, flow cytometry, and transwell assay, respectively. The potential binding sites between miR-145-5p and PVT1 or ITGB8 were predicted by online software and verified by luciferase reporter assay. A xenograft tumor model was established to confirm the effect of PVT1 on NSCLC in vivo. We found out that the expression levels of PVT1 and ITGB8 were upregulated in NSCLC tissues and cells. Knockdown of PVT1 or ITGB8 suppressed cell proliferation, migration, invasion and promoted apoptosis in NSCLC cells, which could be reversed by ITGB8 overexpression in NSCLC cells. Moreover, PVT1 could regulate ITGB8 expression via direct binding to miR-145-5p. Furthermore, PVT1 regulated the MEK/ERK pathway by affecting ITGB8 expression. In addition, knockdown of PVT1 inhibited tumor growth, ITGB8 expression, MEK/ERK signaling pathway, and increased miR-145-5p expression in vivo. In conclusion, the knockdown of PVT1 inhibited proliferation, migration, and invasion but induced apoptosis of NSCLC cells by regulating miR-145-5p/ITGB8 axis and inhibiting MEK/ERK signaling pathway, providing a novel avenue for the treatment of NSCLC.

[Clinicopathological characteristics, diagnosis, and treatment of 29 cases of signet ring cell carcinoma of the rectum and sigmoid colon].

Objective: To investigate the clinicopathological characteristics and the therapeutic effects of signet ring cell carcinoma (SRCC) of rectum and sigmoid colon. Methods: Clinical data and the follow-up information of 29 SRCC patients treated in our tertiary care center from 2008 to 2018 were retrospectively reviewed. The clinicopathological features, diagnostic and therapeutic effects, and the prognostic outcomes were analyzed. Results: Among the 29 patients, 17 were male, 12 were female. The average age was (48.7±14.3) years. Colonoscopy revealed the features of diffuse circumferential thickening of the bowel wall in 20/29 cases (69.0%), while in 9/29 cases (31.0%), endoscopic biopsies showed false negative results. Twenty-five% (4/16) and 17.6% (3/17) lesions were misdiagnosed as the inflammatory changes by endoscopic rectal ultrasonography exam and rectal MRI scan, respectively. Thirteen of the 29 patients received the neoadjuvant chemoradiotherapy (NCRT), 27 patients underwent the radical resection surgeries, and 8 underwent the postoperative radiotherapy. With a median follow-up of 38.5 (3.5-87.0) months, the cumulative 3-years overall survival (OS) rate was 54.0%, and the cumulative 3-years disease-free survival (DFS) rate was 43.0%. The OS rates of patients treated with or without NCRT (non-NCRT) were 46.2% and 69.2%, respectively, without significant difference (P>0.05). The DFS rates of patients treated with or without NCRT were 45.8% and 39.2%, respectively, without significant difference (P>0.05). Parameters including age younger than 40 years and tumor size larger than 5 cm were independent potential risk factors for shortened OS (P<0.05). Conclusions: SRCC of the rectum and sigmoid colon is a rare malignant tumor with special clinical manifestations. It is younger-onset, highly malignant and with very poor prognosis. Therefore, in-depth researches with focus upon the progress of molecular oncology are urgently needed to substantially improve the therapeutic effect of this disease.

[The clinical significance of plasma PTX3 in patients with secondary hemophagocytic lymphohistiocytosis].

Objective: To investigate the significance of plasma pentraxin 3 (PTX3) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). Methods: Plasma PTX3 levels were tested by ELISA in 48 newly diagnosed sHLH patients, 18 healthy volunteers and 9 lymphoma controls in the First Affiliated Hospital of Nanjing Medical University from January 2017 to July 2019. Clinical parameters were collected, and the correlations with PTX3 levels were analyzed. Results: PTX3 level in newly diagnosed group was significantly higher than that of healthy control group [16.29(1.17-66.00) vs. 0.76(0.01-7.86) µg/L, P<0.01]. Patients with lymphoma-associated HLH(LHLH) had higher plasma level of PTX3 than Fhose with infection-associated HLH (IHLH) [24.29(3.36-66.00) vs. 9.56(1.17-36.50)µg/L, P<0.05]. Plasma PTX3 levels in 48 sHLH patients were positively correlated with serum ferritin (P<0.05). Receiver operating characteristic (ROC) curve for plasma PTX3 levels of sHLH and healthy controls produced a cutoff value at 3.9 µg/L, with its 86.7% sensitivity and 94.4% specificity. And ROC analysis showed that PTX3 17.5 µg/L was the critical value for diagnosis of LHLH from non-LHLH group, that the sensitivity and specificity were 63.0% and 76.2% respectively. The 1-year overall survival (OS) rate in patients with PTX3≥17.5 µg/L was significantly lower in those with PTX3<17.5 µg/L (18.5% vs. 75.8%, P<0.01). Conclusion: These results indicate the potential of PTX3 as a biomarker for diagnosis and prognosis in patients with sHLH.

[Quantitative evaluation of early stage blood flow change status after radiofrequency ablation based on multi-slice spiral CT whole-liver perfusion imaging on small hepatocellular carcinoma].

Objective: To investigate the blood flow change status in early stage tumor-related areas of hepatocellular carcinoma and its clinical significance after radiofrequency ablation using multi-slice spiral CT whole-liver perfusion imaging technology. Methods: 21 cases of primary liver cancer that underwent CT-guided radiofrequency ablation were included. CT perfusion scans were divided into four groups according to the time points of CT scans (before surgery, immediately after surgery and 1 and 3 month after surgery), and then blood perfusion parameters of the corresponding areas of the tumor were measured. Statistical analysis was performed using two independent samples of non-parametric Wilcoxon rank-sum test. The differences of blood perfusion parameters between tumor or ablation lesion and background liver parenchyma, paratumor tissue or inflammatory response zone were compared before, immediately and 1 and 3 months after surgery, respectively. Results: (1) The hepatic arterial perfusion (HAP) and hepatic arterial perfusion index (HPI) of cancerous liver tumors and background liver parenchyma was significantly increased (P < 0.01). The total liver perfusion (TLP) was higher than the background liver parenchyma (P = 0.01 < 0.05). The time to peak (TTP) was significantly lower than background liver parenchyma (P < 0.01); (2) The perfusion parameters of HAP, PVP and TLP were lower than the background liver parenchyma in the complete ablation lesions immediately after radiofrequency ablation and 1 and 3 months after surgery, and the difference was statistically significant (P < 0.05); (3) The inflammatory response zone of ablation lesions of HAP, HPI, and TLP were gradually decreased with the extended postoperative time and TTP was gradually increased, while PVP did not change significantly; (4) HAP, HPI, and TTP were compared between the tumor and the tumor inflammatory response zone immediately after surgery, and 1 and 3 months after surgery, and the difference was statistically significant (P < 0.01). However, there was no statistically significant difference between PVP and TLP (P > 0.05). Conclusion: CT whole-liver perfusion imaging can precisely evaluate the early stage blood flow change status in peritumor and tumors before and after radiofrequency ablation and then objectively evaluate tumor's blood supply and therapeutic effect on hepatocellular carcinoma.

[Quantitative assessment of hepatic and splenic blood flow status in patients with hypersplenism of different degrees based on multi-slice spiral CT whole-liver perfusion imaging].

Objective: To investigate the differences and changes of blood flow status of splenic volume, common hepatic artery, splenic arteriovenous, inner diameter of portal vein and hepatic in patients with hypersplenism of different degrees using multi-slice spiral CT whole-liver perfusion model. Methods: 42 cases with hypersplenism of chronic hepatitis B with cirrhosis and 15 cases without hepatosplenic disease were collected as controls. All patients underwent multi-slice spiral CT whole-liver perfusion imaging. (1) The differences of spleen volume, common hepatic artery, splenic arteriovenous, and portal vein diameter between different degrees of hypersplenism and the control group were measured and compared. (2) The correlation between spleen volume and the inner diameter of each related vessels were analyzed and compared. (3) The values of perfusion parameters related to the five lobes of the liver in Couinaud segments based on hepatic artery perfusion (HAP), portal venous perfusion (PVP), total hepatic perfusion (TLP) and hepatic artery perfusion index (HPI) were measured and compared. One-way ANOVA was used to analyze the measurement data. The correlation between the spleen volume and the inner diameter of each blood vessel was analyzed by Pearson's correlation analysis. Results: (1) spleen volume and the inner diameter of splenic artery, splenic vein and portal vein in the cirrhotic hypersplenism group were significantly larger than control group, and the difference was statistically significant (F = 37.108, 17.484, 23.124, 13.636, P < 0.05). (2) spleen volume and the inner diameter of splenic artery, vein and portal vein in the moderate and severe hypersplenism groups were significantly larger than the mild hypersplenism group, and the difference was statistically significant (F = 25.418, 13.293, 15.136, 7.093, P < 0.05), but there was no statistically significant difference between the moderate and severe hypersplenism groups (P > 0.05). (3) The inner diameter of splenic vein, portal vein, and splenic artery was positively correlated with spleen volume (r = 0.680, 0.548, and 0.726). (4) PVP and TLP of the whole liver in hypersplenism group were lower than control group (P < 0.05), and the differences were statistically significant (P < 0.05). HPI in the right posterior lobe of the liver in the moderate and severe hypersplenism group was higher than mild hypersplenism group (F = 3.555, 4.570, P < 0.05), and there was no significant difference in the HAP in the whole liver among the groups (P > 0.05), but the HAP in the whole liver in the severe hypersplenism group was lower than control, mild and moderate hypersplenism group. Conclusion: The inner diameter of the splenic arteriovenous in patients with hypersplenism of different degrees has widened to varying degrees, and is consistent with the increase in spleen volume, particularly in moderate and severe cases. Portal venous perfusion and total liver perfusion in patients with hypersplenism of different degrees have declined and the hepatic arterial perfusion in patients with severe hypersplenism is significantly reduced.