Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.

Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Osteoporosis is associated with depression among older adults: a nationwide population-based study in the USA from 2005 to 2020.

OBJECTIVES: The global prevalence of osteoporosis is rising, yet it is unclear whether people with osteoporosis have a higher risk of depression than those without osteoporosis. STUDY DESIGN: A cross-sectional study. METHODS: We used nationally representative data from the US National Health and Nutrition Examination Survey (NHANES) in 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2020. The diagnosis of osteoporosis was based on the bone mineral density of the femoral neck measured by dual-energy X-ray absorptiometry. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a score ≥5 as depressive symptoms and a score ≥10 as probable depression. We used logistic regression models to evaluate the association between osteoporosis and depressive symptoms and probable depression. RESULTS: We included 11,603 adults (aged 50 years and older, 52.3% male) and observed 5.2% of them had osteoporosis. 31.9% of these osteoporotic people had depressive symptoms, and 10.0% had probable depression. Compared to participants without osteoporosis, those with osteoporosis were 1.73 times more likely to experience depressive symptoms (odds ratio [OR] = 1.73, 95% confidence interval [CI] 1.20-2.50) and 1.91 times more likely to experience probable depression (OR = 1.91, 95% CI 1.02-3.59), after adjusting for sex, age, race/ethnicity, education, marital status, family income, body mass index, smoking, physical activity, and alcohol abuse. Moderate-to-vigorous activities mediated the associations between osteoporosis and depression and depressive symptoms. CONCLUSIONS: Osteoporosis is an independent risk factor for depression. This study highlights the need to evaluate the mental well-being of patients with osteoporosis in clinical and primary health care.

[Specimen extraction through natural orifices with Cai tubes in gastrointestinal surgery: a single-institute series of 234 cases].

Objective: To investigate the feasibility of Cai tube-assisted natural orifice specimen extraction surgery (NOSES) in gastrointestinal surgery. Methods: This was a descriptive case-series study. Inclusion criteria: (1) colorectal or gastric cancer diagnosed by preoperative pathological examination or redundant sigmoid or transverse colon detected by barium enema; (2) indications for laparoscopic surgery; (3) body mass index <30 kg/m2 (transanal surgery) and 35 kg/m2 (transvaginal surgery); (4) no vaginal stenosis or adhesions in female patients undergoing transvaginal specimen extraction; and (5) patients with redundant colon aged 18-70 years and a history of intractable constipation for more than 10 years. Exclusion criteria: (1) colorectal cancer with intestinal perforation or obstruction, or gastric cancer with gastric perforation, gastric hemorrhage, or pyloric obstruction; (2) simultaneous resection of lung, bone, or liver metastases ; (3) history of major abdominal surgery or intestinal adhesions; and (4) incomplete clinical data. From January 2014 to October 2022, 209 patients with gastrointestinal tumors and 25 with redundant colons who met the above criteria were treated by NOSES utilizing a Cai tube (China invention patent number:ZL201410168748.2) in the Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University. The procedures included eversion and pull-out NOSES radical resection in 14 patients with middle and low rectal cancer, NOSES radical left hemicolectomy in 171 patients with left-sided colorectal cancer, NOSES radical right hemicolectomy in 12 patients with right-sided colon cancer, NOSES systematic mesogastric resection in 12 patients with gastric cancer, and NOSES subtotal colectomy in 25 patients with redundant colons. All specimens were collected by using an in-house-made anal cannula (Cai tube) with no auxiliary incisions. The primary outcomes included 1-year recurrence-free survival (RFS) and postoperative complications. Results: Among 234 patients, 116 were male and 118 were female. The mean age was (56.6±10.9) years. NOSES was successfully completed in all patients without conversion to open surgery or procedure-related death. The negative rate of circumferential resection margin was 98.8% (169/171) with both two positive cases having left-sided colorectal cancer. Postoperative complications occurred in 37 patients (15.8%), including 11 cases (4.7%) of anastomotic leakage, 3 cases(1.3%) of anastomotic bleeding, 2 cases (0.9%) of intraperitoneal bleeding, 4 cases (1.7%) of abdominal infection, and 8 cases (3.4%) of pulmonary infection. Reoperations were required in 7 patients (3.0%), all of whom consented to creation of an ileostomy after anastomotic leakage. The total readmission rate within 30 days after surgery was 0.9% (2/234). After a follow-up of (18.3±3.6) months, the 1-year RFS was 94.7%. Five of 209 patients (2.4%) with gastrointestinal tumors had local recurrence, all of which was anastomotic recurrence. Sixteen patients (7.7%) developed distant metastases, including liver metastases(n=8), lung metastases(n=6), and bone metastases (n=2). Conclusion: NOSES assisted by Cai tube is feasible and safe in radical resection of gastrointestinal tumors and subtotal colectomy for redundant colon.

[The influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury].

Objective: To examine the influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury. Methods: From January 2014 to February 2019,the clinical data of 78 patients diagnosed with pelvic ring injury involving sacroiliac joints and treated with bionic reduction and internal fixation at Honghui Hospital Affiliated to Medical College of Xi'an Jiaotong University were retrospectively analyzed.There were 48 males and 30 females,aged (48.3±8.3)years (range:28 to 68 years).After bionic reduction and internal fixation,the patients were grouped according to the maximum displacement distance (d) of sacroiliac joint residual on the damaged side measured by CT examination. Patients with d≤5 mm were included in anatomical bionic reduction group,and patients with d>5 mm were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,according to the direction of residual displacement,the patients were divided into separation displacement group and anterior-posterior displacement group. The X-ray examination was performed immediately and at the last follow-up after operation.If sacroiliac joint was relocated,or internal plant loosening,displacement,fracture and re-displacement of fracture,it was defined as internal fixation failure.Majeed pelvic fracture scoring system was used to evaluate the postoperative functional status of the two groups,and visual analogue scale (VAS) was used to evaluate the postoperative pain.Comparison between groups was performed by completely random design ANOVA,χ2 test,Fisher's exact test,Mann-Whitney U and Kruskal-Wallis H test. Results: According to the CT examination,28 cases were included in anatomical bionic reduction group,and 50 cases were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,27 cases were divided into separation displacement group and 23 cases were in anterior-posterior displacement group.There was no significant difference in general data among anatomical bionic reduction group,separation displacement group and anterior-posterior displacement group (P>0.05). The follow-up time was (37.8±6.6) months (range:25 to 51 months). At the last follow up,the excellent and good rate of Majeed score in anatomical bionic reduction group was 96.4%(27/28),which was better than that in separation displacement group(74.1%(20/27)) and anterior-posterior displacement group (30.4%(7/23)),the difference was statistically significant (Z=-6.479,P<0.01;Z=-6.256,P<0.01); and the good rate of the separation displacement group was better than that of the anterior-posterior displacement group(Z=-3.607,P<0.01).The VAS of anatomical bionic reduction group (17 cases with 0 point, 11 cases with 1 to 3 points) were lower than that of the displacement group (6 cases with 0 point,16 cases with 1 to 3 points,5 cases with 4 to 6 points) and anterior-posterior displacement group (3 cases with 0 point,7 cases with 1 to 3 points,13 cases with 4 to 6 points),the difference was statistically significant (Z=-3.515,P<0.01;Z=-3.506,P<0.01),and there was no difference between separation displacement group and anterior-posterior displacement group.Total of 8 cases of internal fixation failure occurred,and the failure rate of anatomical bionic reduction group (0,0/28) was lower than that of the separation displacement group (11.1%,3/27) and anterior-posterior displacement group (21.7%,5/23) (P=0.111,P=0.014),and there was no difference between separation displacement group and anterior-posterior displacement group(P=0.444). Conclusions: In the bionic reduction and internal fixation of pelvic fracture involving sacroiliac joint injury,the functional status,pain and internal fixation failure rate of patients with anatomical bionic reduction of sacroiliac joint are significantly better than those in the non-anatomical bionic reduction.The functional recovery of patients with separation displacement is better than that of the patients with anterior and posterior displacement.

[Effects of high-flow nasal oxygen combined with early extubation on the incidence of respiratory adverse events during emergence from general anesthesia in children undergoing adenoid-tonsillectomy].

Objective: To investigate the effects of high-flow nasal oxygen (HFNO) combined with early extubation on the incidence of respiratory adverse events (RAE) during emergence from general anesthesia in children undergoing adenoid-tonsillectomy. Methods: From December 2021 to January 2022, 40 pediatric patients [21 males, 19 females, with a median age of 4 (4, 5) years] undergoing tonsillectomy and/or adenoidectomy in Eye & ENT Hospital of Fudan University were randomly divided into two groups: HFNO-assisted early extubation group (Group H, n=20) and conventional extubation group (Group C, n=20) by using a random number table. After entering the post-anesthesia care unit (PACU), the patients in group H received humidified and heated oxygen (flow rate: 25 L/min) through a nasal cannula until their consciousness regained. After patient's spontaneous breathing resumed for 10 min, the oral endotracheal tube was removed. Patients in group C did not receive HFNO. The oral endotracheal tube was removed after the patient's spontaneous breathing resumed for at least 10 min with signs of tube intolerance, or 20 min without signs of tube intolerance. During the PACU stay, the incidence of RAE, the incidence of cough, the application rate of intensive care strategy, the time to extubation, the duration of PACU stay, and vital signs at spontaneous breathing resuming and extubation in each group were recorded. Results: In Group H, the total incidence of RAE [30% (6/20) vs 65% (13/20), P=0.027], the incidence of cough [10% (2/10) vs 45% (9/20), P=0.031] and the application rate of intensive care strategy [20% (4/20) vs 55% (11/20), P=0.048] during PACU stay was significantly lower, compared with those of Group C. Likewise, the time to extubation was significantly shorter [(33.4±4.5) min vs (42.7±5.3) min, P<0.001]. However, there was no statistically significant difference in the duration of PACU stay, the vital signs at the time of spontaneous breathing resuming and extubation between the two groups (P>0.05), except that the end-tidal carbon dioxide partial pressure (PETCO2) at the time of extubation in group H was significantly higher than group C [(52.9±9.4) mmHg vs (48.9±3.1) mmHg (1 mmHg=0.133 kPa), P<0.001]. Conclusion: HFNO combined with early extubation can significantly reduce the incidence of RAE in children undergoing adenoid-tonsillectomy during the emergence from general anesthesia.

[Sensitization characteristics of Juniperus chinensis pollen in Beijing area].

Objective: To investigate the sensitization characteristics of Juniperus chinensis pollen in patients with allergic rhinitis and/or allergic asthma in Beijing area, and to explore the characteristics of Juniper chinensis pollen sensitized population. Methods: Patients with suspected allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were selected in this study. Skin prick test (SPT) was performed with Juniper chinensis pollen allergen reagent to compare different age and disease allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results: A total of 8 380 patients were enrolled in the end. The total positive rate of Juniper chinensis pollen SPT reached 49.92% (4 183/8 380). The positive rate of Juniper chinensis pollen SPT was highest in the 10-14 age group, reaching 60.99% (283/464). Compared with other age groups, there was a statistical difference (χ²=266.77, P<0.01). The SPT positive rate of patients aged less than 10 years increased with the increase of age, while the SPT positive rate of patients aged over 40 years decreased with the increase of age. Single Juniper chinensis pollen was less allergenic, accounting for about 25.05% (1 048/4 183), and the patients' age was (35.21±12.39) years. Regardless of single Juniper chinensis pollen or other pollen allergies, allergic rhinitis was the main disease. Among the patients with SPT positive Juniper chinensis pollen combined with other inhaled pollen allergens, willow pollen accounted for the first (74.99%). The positive rate of Juniper chinensis pollen was the highest in patients with single allergic rhinitis, accounting for 52.05% (3 797/7 295), and the rate in patients with single allergic asthma was the lowest, accounting for 17.49% (53/303), with statistically difference (χ²=138.99, P<0.01). Conclusions: Juniper chinensis pollen is highly sensitized in patients with allergic rhinitis and/or allergic asthma in Beijing . The positive rate of SPT is highest among 10-14 age group, most of which showed strong positive reaction, and allergic rhinitis is more common in Juniper chinensis pollen sensitization diseases.

[Effect of postmastectomy radiotherapy on survival outcomes of patients with metaplastic breast cancer].

OBJECTIVE: To evaluate the effect of postmastectomy radiotherapy (PMRT) on the overall survival (OS) and breast cancer-specific survival (BCSS) of patients with metaplastic breast cancer (MpBC) in comparison with those of patients with invasive ductal breast carcinoma (IDC). METHODS: We selected the patients with pathologically confirmed MpBC and IDC who either received PMRT or not from the archived cases (from January, 1998 to December, 2016) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. In total, 31 982 patients were selected, including 308 patients with MpBC and PMRT, 629 with MpBC and PMRT, and 31 045 with IDC and PMRT. All the included patients were above 18 years of age without distant metastases or a second primary cancer and underwent radical surgery. Baseline characteristics of the patients were compared among the 3 subgroups, and multivariate Cox regression and Kaplan-Meier analyses were performed for analyzing the prognostic factors of MpBC, OS, and BCSS. RESULTS: The majority (81.2%) of patients with MpBC were older than 50 years, had pathological grade III (68%), and were negative for ER (75.9%) and PR (79.8%) and in stage T2-3 (71.3%) and N0-1 (85.6%). Multivariate Cox regression analysis showed that age, T stage, N stage, PMRT, and chemotherapy were significantly associated with the prognosis of patients with MpBC (P < 0.05), while pathological grade, ER status, or PR status did not significantly affect the prognosis (P>0.05). Kaplan-Meier analysis showed that the patients with MpBC and PMRT had better OS (HR=1.394, 95% CI: 1.125-1.727; P < 0.05) and BCSS (HR=1.390, 95% CI: 1.074-1.800; P < 0.05) than those with MpBC who did not receive PMRT; but after PMRT, the patients with MpBC had worse OS (HR=1.626, 95%CI: 1.386-1.908; P < 0.001) and BCSS (HR=1.710, 95% CI: 1.418-2.062; P < 0.001) as compared with those with IDC. CONCLUSION: MpBC has unique clinicopathological features. In patients with MpBC, age, T stage, N stage, radiotherapy and chemotherapy are all the prognostic factors affecting the survival outcomes, and PMRT can improve the OS and BCSS of the patients.

Mechanism of curcumin against myocardial ischaemia-reperfusion injury based on the P13K/Akt/mTOR signalling pathway.

OBJECTIVE: To investigate the pharmacodynamic mechanism of curcumin against myocardial ischaemia-reperfusion injury by regulating the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/rapamycin target protein (mTOR) signalling pathway. MATERIALS AND METHODS: The left anterior descending coronary artery was ligated for 30 min and reperfused for 3 h to establish an ischaemia-reperfusion injury model. The electrocardiogram (ECG) detection of rats was performed, and the degree of myocardial infarction was determined by 2,3,5-triphenyltetrazolium chloride staining. The expression levels of serum creatine kinase isoenzyme (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO) and other related indicators were detected. The protein expressions of mTOR, phosphorylated (p)-mTOR, AKT and p-AKT were detected by Western blotting, whereas the expressions of Bcl-2 and Bax were detected by real-time polymerase chain reaction. RESULTS: The results showed that compared with the model group, curcumin could improve the ECG findings, reduce the scope of myocardial infarction, reduce the expression levels of CK-MB, LDH, AST, MDA, NO and increase those of SOD and GSH. Curcumin can also down-regulate the expression of Bax and up-regulate the protein levels of Bcl2, p-mTOR and p-AKT (p < 0.05 or p < 0.01). CONCLUSIONS: This study shows that curcumin has a significant protective effect on myocardial ischaemia-reperfusion, and its mechanism may be related to the activation of PI3K/AKT/mTOR signalling pathway and inhibition of inflammation, apoptosis and oxidative stress.

[Analysis of characteristics of Chenopodiaceae pollen induced seasonal allergic rhinitis in the Inner Mongolian grassland region of China].

Objective: To analyze the clinical characteristics of Chenopodiaceae pollen induced seasonal allergic rhinitis (SAR) as well as the distribution and sensitization characteristics of Chenopodiaceae pollen in Inner Mongolia grassland of northern China. Methods: From May 2015 to August 2015, using stratified, cluster and random sampling, a field interviewer-administered survey study and skin prick test (SPT) were conducted in six areas of Inner Mongolia grassland (Xilinhot, Erenhot, Duolun, Tongliao, Jarud, Kailu), and pollen monitoring was carried out in the above six areas from January 1 to December 31 of 2015. The clinical characteristics of Chenopodiaceae pollen induced SAR, distribution and sensitization characteristics of Chenopodiaceae pollen in these regions were observed. SAS software 9.4 was used for data processing. Results: A total of 6 043 subjects completed the study. The prevalence of Chenopodiaceae pollen induced SAR was 13.2% (795/6 043). The highest prevalence was found in the 18-39 age group. Subjects from urban areas showed higher prevalence of SAR than rural areas (61.2% vs 37.9%, P<0.001). There was significant regional difference in the prevalence rate of Chenopodiaceae pollen induced SAR among the above six areas (Xilinhot 21.5%, Erenhot 17.8%, Duolun 8.9%, Tongliao 6.9%, Jarud 15.3%, Kailu 9.7%, P<0.001). The main clinical symptoms of Chenopodiaceae pollen induced SAR were sneezing (96.5%) and nasal itching (92.2%). Eye itching was more obvious among the ocular symptoms (69.1%), while fatigue (32.1%) and drowsiness (31.5%) were more prominent among other related symptoms. Among comorbidities of Chenopodiaceae pollen induced SAR, allergic conjunctivitis accounted for 71.4% (568/795), food allergy accounted for 86.7% (689/795) and asthma accounted for 16.7% (133/795). The peak of Chenopodiaceae pollen spread was in August. The prevalence of Chenopodiaceae pollen induced SAR was positively correlated with the concentration of Chenopodiaceae pollen (R2=0.78, P=0.043). The SPT positive rate of Chenopodiaceae pollen was 21.2% (1 282/6 043), and Xilinhot had the highest rate in six regions (28.0%, 236/842). Conclusions: The prevalence of Chenopodiaceae pollen induced SAR in Inner Mongolia grassland stays at a high level. Sneezing is the most obvious symptom of SAR. The peak of Chenopodiaceae pollen spread is in August and the prevalence of Chenopodiaceae pollen induced SAR is positively correlated with the pollen concentration.

New biomarker for lung cancer - focus on circSETD3.

In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinib-resistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.

Probiotic Lactobacillus rhamnosus GG (LGG) restores intestinal dysbacteriosis to alleviate upregulated inflammatory cytokines triggered by femoral diaphyseal fracture in adolescent rodent model.

OBJECTIVE: The aim of the study was to examine the influence of femoral shaft fracture on systemic inflammation and gut microbiome in adolescent rats and evaluate the anti-inflammatory effect of Lactobacillus rhamnosus GG (LGG) and its regulation of intestinal flora, as well as illustrate the mechanism by which LGG ameliorates the inflammatory response and restores intestinal dysbacteriosis. MATERIALS AND METHODS: Twenty-four male Sprague Dawley rats of 5 to 6 weeks of age were subjected to a standard femoral shaft fracture and internally fixed with LGG supplementation in advance or on the same day of injury or with saline solution for 1 week. The levels of TNF-α, IL-6, IL-10, and CRP were assessed using standard protocols. Furthermore, gut microbiota composition was analyzed in the fecal samples using 16S rDNA gene sequencing, and the relationship between gut microbiota variation and inflammatory response was tested. RESULTS: The serum indices of the above-mentioned inflammatory cytokines were significantly increased, and the gut microbial balance was significantly disturbed in adolescent rats by diaphyseal fractures of the femur and surgery. Moreover, L. rhamnosus strains manipulated the gut microbiota by decreasing the relative abundance of Proteobacteria and increasing that of Firmicutes, Actinobacteria and Bacteroidetes, which in turn increased the levels of IL-10 and alleviated the levels of IL-6, CRP, and TNF-α. CONCLUSIONS: LGG exhibited anti-inflammatory effects by alleviating the inflammatory response and regulating the gut microbiota in adolescent rats who underwent skeletal fracture and surgery. Our results suggested that the L. rhamnosus strains could be considered as an alternative dietary supplement for the prevention or treatment of skeletal injury and its associated complications.

CircRNA UBAP2 facilitates the progression of colorectal cancer by regulating miR-199a/VEGFA pathway.

OBJECTIVE: The aim of this study is to explore the regulatory mechanism of circRNA UBAP2 (circUBAP2) in colorectal cancer (CRC). PATIENTS AND METHODS: The expression levels of circUBAP2, miR-199a, and VEGFA in tissues and cell lines were detected by RT-qPCR. The cell proliferation was examined by CCK-8 and colony formation assays. The migration and invasion abilities were evaluated by wound healing and transwell assays, respectively. Bioinformatics analysis and Luciferase activity assay were applied to determine the interaction between genes. RESULTS: The expression of circUBAP2 was upregulated in CRC tissues and cell lines, and depletion of circUBAP2 suppressed the cell proliferation, migration, and invasion of CRC. Furthermore, miR-199a inhibitor abrogated the suppressive effect of circUBAP2 knockdown on CRC progression. Vascular endothelial growth factor A (VEGFA) was identified as a downstream target gene of miR-199a, and overexpression of VEGFA rescued the tumor phenotypes attenuated by circUBAP2 knockdown or miR-199a overexpression. CONCLUSIONS: Our findings demonstrated that circUBAP2 facilitated CRC progression by sponging miR-199a to upregulate VEGFA. These findings implied that circUBAP2 may be a potential therapeutic biomarker for CRC.

LncRNA ROR promotes proliferation of endometrial cancer cells via regulating Notch1 pathway.

OBJECTIVE: The aim of this study was to investigate the effects of long non-coding ribonucleic acid regulator of reprogramming (lncRNA ROR) on the proliferation and apoptosis of endometrial cancer (EC) cells, and to explore its possible underlying mechanism. PATIENTS AND METHODS: The expression levels of lncRNA ROR and Notch1 in EC tissues were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The changes in Notch1 protein were detected via Western blotting. Subsequently, the regulatory mechanism of lncRNA ROR on Notch1 was analyzed using Luciferase reporter gene assay. Moreover, the changes in cell proliferation and apoptosis were determined through cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. RESULTS: Both lncRNA ROR and Notch1 were highly expressed in EC tissues (p<0.05). After overexpression of lncRNA ROR, HEC-1A cells had significantly enhanced proliferation (p<0.05) and weakened apoptosis (p<0.05). Meanwhile, the mRNA and protein levels of Notch1 rose remarkably compared with those in control group (p<0.05). Luciferase reporter gene assay revealed that lncRNA ROR could bind to the Notch1 regulatory factor miR-34a and inhibit its activity. CONCLUSIONS: LncRNA ROR regulates the proliferation and apoptosis of EC cells via promoting the expression of Notch1 protein.

Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.

We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.

Immune checkpoint inhibitor-associated pituitary adverse events: an observational, retrospective, disproportionality study.

PURPOSE: The aim of this study was to identify and characterize immune checkpoint inhibitors (ICIs)-associated pituitary adverse events (AEs). METHODS: This is a retrospective disproportionality study based on VigiBase, the World Health Organization (WHO) global database of individual case safety reports (ICSRs), with a study period from January 1, 2011 to March 6, 2019. Information component (IC) and reporting odds ratio (ROR) are measures of disproportionate analysis. IC was used to evaluate the association between ICIs and pituitary AEs, while ROR was used to evaluate the differences in reporting of pituitary AEs between different ICI subgroups. RESULTS: The following ICI-associated pituitary diseases have been increasingly reported: hypophysitis (835 reports; information component 6.74 [95% CI 6.63-6.83]), hypopituitarism (268; 6.12 [95% CI 5.92-6.27]), pituitary enlargement (28; 5.19 [95% CI 4.57-5.63]). The anti-CTLA-4 subgroup had a stronger association with hypophysitis/hypopituitarism than the anti-PD (anti-PD-1 or anti-PD-L1) subgroup (ROR 8.0 [95% CI 6.7-9.6]). Among ICI-associated hypophysitis/hypopituitarism cases, the proportion of male was higher than female (630 [63.9%] vs 356 [36.1%]). Anti-CTLA-4 subgroup and ICI combination (nivolumab plus ipilimumab) subgroup both had a significantly earlier onset time than anti-PD subgroup (67 days [IQR 48-87]; 90 [IQR 34-155]; 140 [IQR 62-218], both p < 0.05). Other endocrinopathies that co-occurred with hypophysitis/hypopituitarism were adrenal insufficiency, thyroid dysfunction, diabetes mellitus and diabetes insipidus. Gastrointestinal disorder was the most common concurrent disease except for endocrinopathies. CONCLUSIONS: ICI-associated pituitary adverse events have significantly increased, and their clinical characteristics should be kept in mind by oncologists and endocrinologists who manage patients treated by immunotherapy.

[Percutaneous full-endoscopic removalof lumbar dumbbell tumors viatransforaminal approach].

Objective: To investigate the novel application and effectof Percutaneous Full-Endoscopic transforaminal approach for lumbar dumbbell tumors. Methods: A retrospective analysis of 12 cases of lumbar dumbbell tumors was conducted by Percutaneous full-endoscopic transforaminal approach in the Department of Neurosurgery, Fujian Medical University Union Hospital from Feb, 2018 to Jul, 2019. According to Eden classification, 5 cases in type Ⅲ and 7 cases in type Ⅳ. The Japanese Orthopaedic Association (JOA) score and Pain Visual analogue Scale (VAS) were used to compare the recovery of neurological function before and after surgery. Results: All the 12 tumors were completely removed in one stage. The pathological reports were all schwannomas (WHO grade Ⅰ). The VAS scores were significantly decreased compared with preoperative ones (P<0.001). The JOA scores were significantly improved without obvious complications and spinal instability. Median length of follow-up was 14 months with a range of 4 months to 20 months, there is no tumor recurrence and spinal instability. Conclusion: In the treatment of lumbar dumbbell spinal tumor, the full endoscopic transforaminal approach is a novel, safe and effective surgical procedure which removes the tumors intra-foramen and extra-foramen with less damage of spine, smaller possibility of instability and faster recovery.

Evaluation of two intensive care models in relation to successful extubation after cardiac surgery.

OBJECTIVE: To compare outcomes between intensivist-directed and cardiac surgeon-directed care delivery models. DESIGN: This retrospective, historical-control study was performed in a cohort of adult cardiac surgical patients at Zhongshan Hospital (Fudan University, China). During the first phase (March to August 2015), cardiac surgeons were in charge of postoperative care while intensivists were in charge during the second phase (September 2015-June 2016). Both phases were compared regarding successful extubation rate, intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. SETTING: Tertiary Zhongshan Hospital (Fudan University, China). PATIENTS: Consecutive adult patients admitted to the cardiac surgical ICU (CSICU) after heart surgery. INTERVENTIONS: Phase I patients treated by cardiac surgeons, and phase II patients treated by intensivists. MAIN VARIABLES OF INTEREST: Successful extubation, ICU LOS and in-hospital mortality. RESULTS: A total of 1792 (phase I) and 3007 patients (phase II) were enrolled. Most variables did not differ significantly between the two phases. However, patients in phase II had a higher successful extubation rate (99.17% vs. 98.55%; p=0.043) and a shorter median duration of mechanical ventilation (MV) (18 vs. 19h; p<0.001). In relation to patients with MV duration >48h, those in phase II had a comparatively higher successful extubation rate (p=0.033), shorter ICU LOS (p=0.038) and a significant decrease in in-hospital mortality (p=0.039). CONCLUSIONS: The intensivist-directed care model showed improved rates of successful extubation and shorter MV durations after cardiac surgery.

A Linear Regression Predictor for Identifying N6-Methyladenosine Sites Using Frequent Gapped K-mer Pattern.

N6-methyladenosine (m6A) is one of the most common and abundant modifications in RNA, which is related to many biological processes in humans. Abnormal RNA modifications are often associated with a series of diseases, including tumors, neurogenic diseases, and embryonic retardation. Therefore, identifying m6A sites is of paramount importance in the post-genomic age. Although many lab-based methods have been proposed to annotate m6A sites, they are time consuming and cost ineffective. In view of the drawbacks of the intrinsic methods in RNA sequence recognition, computational methods are suggested as a supplement to identify m6A sites. In this study, we develop a novel feature extraction algorithm based on the frequent gapped k-mer pattern (FGKP) and apply the linear regression to construct the prediction model. The new predictor is used to identify m6A sites in the Saccharomyces cerevisiae database. It has been shown by the 10-fold cross-validation that the performance is better than that of recent methods. Comparative results indicate that our model has great potential to become a useful and effective tool for genome analysis and gain more insights for locating m6A sites.