bluuebunny/crossref_metadata_2025 huggingface dataset:
DL-3-n-Butylphthalide Improves Physical and Cognitive Performance of Animals with Acute and Chronic Hypobaric Hypoxia
Authors: Xu Gang , Shi Yikun , Sun Binda , Liu Lu , E Guoji , He Shu , Zhang Jianyang , Liu Bao , Hu Qiu , Chen Jian , Gao Yuqi , Zhang Erlong
Published: July 2020

Background: Studies revealed the protective effect of DL-3-n-butylphthalide (NBP) against ischemic hypoxia diseases. However, the role of NBP in animals with hypobaric hypoxia is elusive. This study investigated the effect of NBP on animals with acute and chronic hypobaric hypoxia.Methods: SD rats and Kunming mice administrated with NBP (90, 180 and 360 mg/kg for mice, and 60, 120, and 240 mg/kg for rats) were located in 10,000 m hypobaric hypoxia chamber. And survival analysis of animals implied that NBP could significantly improve survival percent at 30 min. Then, treated animals were evaluated for exhaustive time and exhaustive distance in forced exercise wheel-track treadmill and treadmill running experiments at 5,800 m for 3 or 21 days, to evaluate physical functions. Rats were also evaluated for times of active escape, average time of active escape, time of passive escape, and average time of passive escape in a shuttle-box experiment at 5,800 m for 7 or 28 days, to evaluate cognitive functions. ATP level was evaluated in the gastrocnemius muscle and maloaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), lactate, and glutathione peroxiase (GSH-Px) measurements and routine blood tests were detected.Results: Exhaustive time for rats (NBP, 120 and 240 mg/kg) and exhaustive time and distance for mice (NBP, 90 mg/kg) significantly increased under acute hypoxia. And NBP treatment significantly increased the exhaustive time for rats under chronic hypoxia. Moreover, NBP of 120 and 240 mg/kg significantly increased the average time of passive escape under acute and chronic hypoxia. These results suggested that NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px increased under acute and chronic hypoxia. Furthermore, the content of ATP significantly increased, while lactate level significantly decreased. The results presented that NBP could regulate redox homeostasis and improve energy metabolism.Conclusion: NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia by increasing anti-oxidative capacity and energy supply.
Normative Reference Equations of Airway Dynamics Assessed by Whole-Body Plethysmography During Spontaneous Breathing Transitionally Evaluated in Infants, Children and Adults
Authors: Kraemer Richard , Smith Hans-Jürgen , Matthys Heinrich
Published: July 2020

Background In contrast to the conventional parameters of airway dynamics mostly obtained by the two-point approximation method, the effective specific airway resistance (sReff), its reciprocal value the effective specific airway conductance (sGeff) resp., obtained by the integration of the entire tidal breathing loop, features promising target parameters for differentiating between individual functional disease patterns. sReff can be computed as the ratio between the integral of the area enclosed by the plethysmographic shift volume–tidal flow loop, featuring the specific aerodynamic work of breathing (sWOB), and the tidal flow–volume loop, sGeff by the ratio of the integral of the tidal flow–volume loop and the sWOB, respectively. However, normative values for sWOB, sReff and sGeff at resting level are not yet available.Methods We aimed to define reference equations in healthy infants (n=28), children (n=47) and adults (n=273), which incorporates not only the standard anthropometric measures, but also lung volume and breathing pattern indices (including both volume and time indices). Retrospectively exported data were collected from databases of 5 Swiss lung function centres, in which plethysmography (Jaeger Würzburg, Germany) was performed using standard techniques (ATS-ERS criteria) for the assessment of airway dynamics, static lung volumes and forced breathing flow-volume loops.Results Using multi-linear modelling, reference equations of sReff, sGeff, and sWOB could be defined taking as independent parameters apart from anthropometric parameters, also parameters given by the ratio between the tidal volume (VT) and functional residual capacity (FRCpleth), and the ratio between VT and inspiratory time (VT/TI). In addition, we examined the effect of age on the breathing pattern, the relationship between breathing pattern (tidal volume) and timing (inspiratory time).Conclusions An alternative statistical approach to define reference equations of airway dynamics reveals that apart from the subject’s anthropometric measurements, parameters of the magnitude of static lung volumes, the breathing pattern, and the timing of breathing are co-variants of reference equations of airway dynamics over a large age range.
Association of Clinical and Laboratory Variables with In-Hospital Incidence of Deep Vein Thrombosis in Patients with Acute Stroke: A Retrospective Study
Authors: Huang Yucai , Song Kun , Peng Wen , Zhou Yang , Ding Qiong , Li Changluo , Ding Ning
Published: July 2020

Backgrounds: Deep vein thrombosis (DVT) is a serious complication in patients with acute stroke. Early prediction of DVT could enable physicians to perform a proper prevention strategy. We analyzed the association of clinical and laboratory variables with DVT to evaluate the risk of DVT in patients after stroke.Results: Acute stroke patients admitted to the Changsha Central Hospital between January 2016 and December 2019 with length of stay in hospital≥30 d were included. Clinical and laboratory variables for DVT at baseline were collected, and the diagnosis of DVT was confirmed by ultrasonography. Risk factors were developed by Multivariate logistic regression analysis. A total of 101 patients were included in the study, of which 77.2%(78/101) were diagnosed ischemic stroke and 22.8%(23/101)were confirmed hemorrhagic stroke. The overall incidence of DVT after acute stroke within 30 days was 19.8%(20/101). The level of D-dimer when DVT detected was significant increased than that on admission. Pulmonary infection and increased muscle tone as independent relevant factors for DVT were confirmed. Conclusions: Pulmonary infection as a risk factor and increased muscle tone as a protector factor for DVT were identified in patients after stroke and the significant change in level of D-dimer could be a warning for DVT occurrence. It helps with taking early managements to reduce the incidence of DVT in patients after stroke.
Effects of Different Anaesthesia Methods on Perioperative Cellular Immune Function and Long-term Outcomes in Patients Undergoing Radical Resection of Esophageal Cancer: A Prospective Cohort Study
Authors: Cong Xuhui , Zhang Wei , Huang Zhoufeng , Zhang Liyuan , Sun Mingyang , Chang Enqiang , Zhang Jiaqiang
Published: July 2020

Background The present study aimed to analyse the effects of different an anaesthetic method on perioperative cellular immunity and long-term outcomes in patients having undergone oesophageal cancer surgery.Design A Prospective Cohort StudyParticipants 120 cases of patients with oesophageal cancer in the Zhengzhou University People’s Hospital from January 2016 to January 2017 were recruited and randomly split into GA group (general anaesthesia, n=40), PG group (Paravertebral nerve blocks with general anaesthesia, n = 40) and EG group (epidural anaesthesia with general anaesthesia, n=40). Methods Self-rating anxiety scale and visual analogue scale scores were adopted to compare postoperative anxiety and the degree of pain of patients of the three groups. Besides, adverse reactions of patients in the three groups were compared. Pre-operation, the end of operation, postoperative day (POD) 1 and POD 2 levels of interleukin-6 (IL-6), IL-4, tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and the survival of T-cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were measured with by either ELISA or flow cytometry.Results In the PG or EG group, VAS scores were lower, and fewer opioids and vasoactive agents were used, as compared with those of the GA group. In both the EG and PG groups, higher CD3+ and CD4+ cell survival and lower levels of Cor, IL-4 and IL-6 were identified at the end of or after the surgery than those in the GA group. Moreover, the postoperative survival cure of the PG and EG groups was better than that of the GA group.Conclusions The combination of paravertebral nerve blocks or epidural anaesthesia and general anaesthesia may improve the perioperative immune function and the long-term outcome for patients having undergone oesophageal cancer surgery.
Persistently higher serum sCD40L levels are associated with mortality in septic patients
Authors: Liang Yingjian , Zhu Chengrui , Sun Yini , Li Zhiliang , Wang Liang , Liu Yina , Li Xin , ma xiaochun
Published: July 2020

Background
Soluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and in surgical sepsis patients (SS) during the first three days at Intensive Care Unit (ICU) admission, and to observe the association between sCD40L and mortality.
Methods
Time changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with 19 SWS. Serum sCD40L concentration was detected by ELISA. Survival at 28-days was used as the endpoint.
Results
SS had significantly higher sCD40L levels than SWS and control patients. Advanced age (P = 0.023) was observed in the group of nonsurviving patients compared with surviving SS. We observed an association between sCD40L levels ≥ 1028.75 pg/ml at day 2 and 28-days mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P = 0.007).
Conclusions
Septic patients show persistently higher circulating sCD40L levels in the first three days at ICU admission, and it is likely that sCD40L on the day 2 may have a predictive value; thus, serum sCD40L could be used as a reliable biomarker and therapeutic target in sepsis.
Effects of Total Intravenous Anesthesia with Propofol Versus Inhalational Anesthesia with Sevoflurane on Postoperative Quality of Life and Postoperative Delirium in Patients Undergoing Total Knee Arthroplasty: A Randomized, Controlled, Double-Blinded Clinical Trial
Authors: Su Han , Fang Yuxin , Xu Guanghong , Liu Xuesheng
Published: July 2020

Background: The widespread use of total knee arthroplasty(TKA) to treat patients who suffer knee osteoarthritis(KOA) has led to a number of postoperative problems, including the recovery of postoperative quality of life and postoperative delirium(POD). Both problems could cause profound damages to patients and their families. This study assessed and compared the effects of total intravenous anesthesia with propofol versus inhalational anesthesia (sevoflurane) on postoperative quality of life and POD in patients who underwent TKA.Methods: One hundred and fifty patients American Society of Anesthesiologists(ASA) I-III were assessed for inclusion in this study, and randomly divided into inhalational anesthesia with sevoflurane group(group S), and total intravenous anesthesia with propofol group(group P). The primary outcome was postoperative quality of life and secondary outcome was POD.Results: The quality of life at the first month after surgery in group S was better than that in group P(P=0.02). However, there was no significant difference in quality of life between the two groups at 1 day before surgery, 1 day after surgery, 3 days after surgery, 7 days after surgery and 3 months after surgery. In group P, 19 patients (31.1%) had no anxiety/depression problems, 40 patients (65.6%) had moderate problems, and 2 patients (3.3%) had severe problems.In group S, 37 patients (60.6%) had no problems in anxiety/depression, 23 patients (37.7%) had moderate problems, and 1 patient had severe problems (1.7%). These two outcomes had significant differences (P=0.005) .The incidence of POD within 3 days after surgery was 24.6% (15/61) in group P and 36.1% (22/61) in group S. There was no significant difference in the incidence of POD between the two groups (P=0.17).Conclusions: Group S patients have a better quality of life at the first month after surgery in comparison with those in group P regarding anxiety/depression. However, there were no significant differences in the quality of lives between the two groups at 1 day before surgery, 1 day after surgery, 3 days after surgery, 7 days after surgery, and 3 months after surgery. There was also no significant difference in POD. Thus, we concluded that both anesthetic technologies could be extensively used for TKA.Trial registration: This trial was registered at the Chinese Clinical Trial Registry (ChiCRT-IOR-17012428). Date of Registration: 21 Aug. 2017.
CLTRN, regulated by NRF1/RAN/DLD protein complex, enhances radiation sensitivity of hepatocellular carcinoma cells through ferroptosis pathway
Authors: Yuan Yin , Cao Wen , Zhou Hongbing , Qian Haixin , Wang Honggang
Published: July 2020

Background
Radiotherapy is a viable treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, radiation resistance is an issue that needs to be addressed. In this context, cumulative evidence supports the functional roles of a variety of RNA or proteins in radioresistance, and suggests that the modulation of their expression may constitute a novel radiosensitization approach. Here, we investigated the ability of collectrin (CLTRN) to enhance the radiosensitivity in HCC patients for the first time.
Methods
Transcriptome sequencing technology (RNA-seq technology) was used to analyze the transcription-level changes in the genes from the HepG2 cells before and after X-ray irradiation. Combining the results with the HCC tissue RNA-seq data, we determined the ultimate target gene through bioinformatics analysis and cellular verification. A series of cellular and molecular biology techniques were applied in vitro and in vivo to confirm whether CLTRN can enhance radiosensitivity in HCC cells. Subsequently, the downstream action mechanism, the upstream transcription factor, and the interaction proteins of CLTRN were determined.
Results
First, we confirmed the association between CLTRN and radiosensitivity. We observed that CLTRN overexpression led to a significant reduction in the proliferation, migration, and invasion potential of X-ray-irradiated HCC cells, whereas no observable effect was exerted on cell cycle and apoptosis. The same results were observed in nude mice in vivo. Investigation of the gene regulatory mechanism revealed that the genes analyzed at transcriptome level after CLTRN overexpression were mostly enriched in the glutathione metabolic pathway. As glutathione metabolism forms a vital link in ferroptosis, we surmised that CLTRN is associated with ferroptosis. This was confirmed through the detection of cellular iron, ROS level determination, transmission electron microscopy, and monitoring of ferroptosis-related protein indicators. Lastly, we investigated whether nuclear respiratory factor 1 (NRF1) is the upstream transcription factor of CLTRN, and whether dihydrolipoamide dehydrogenase (DLD) and members of the RAS oncogene family (RAN) are its interacting proteins.
Conclusion
Our results indicate that CLTRN is a vital regulator of radiation sensitivity and could serve as a novel therapeutic target or prognostic marker in HCC treatment.
lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p
Authors: Han Shuyi , Xu Yihui , Wang Min , Wang Jun , Wang Jing , Yuan Mingjie , Jia Yanfei , Ma Xiaoli , Wang Yunshan , Liu Xiangdong
Published: July 2020

Background

Gastric cancer (GC) is the fourth common and the second lethal malignancy. Further understanding of the molecular mechanisms of underlying gastric carcinogenesis will enhance the diagnosis and treatment of GC.
Methods

The expression of lncRNA DLEU2 and ETS2 was analysed using GEPIA online analyze, qRT-PCR and immunohistochemistry. siRNAs targeting to lncRNA DLEU2 were designed to reduce the expression of lncRNA DLEU2. miR-30a-5p mimics were purchased to up-regulate the level of miR-30a-5p. The pcDNA3.1-ETS2 vector was synthesized to up-regulate the expression of ETS2. The biological function of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied.
Results

LncRNA DLEU2 was significantly up-regulated in GC tissues. The expression of lncRNA DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of lncRNA DLEU2 inhibited the proliferation, migration and invasion of AGS and MKN-45 cells, and induced cell apoptosis. We also found that miR-30a-5p could directly bind to the 3’ UTR region of ETS2. Moreover, lncRNA DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of lncRNA DLEU2 reduced the protein level of intracellular ETS2 and inhibited the AKT phosphorylation. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by lncRNA DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells. These results showed that lncRNA DLEU2 may regulate GC cells process through miR-30a-5p/ETS2 axis. In addition, hypoxic microenvironment resulted in the accumulation and nucleation of HIF-1α in gastric cancer cells, and up-regulated the expression of DLEU2.
Conclusions

LncRNA DLEU2 was a potential molecular target for GC treatment.
Dihydroartemisinin Sensitizes Esophageal Squamous Cell Carcinoma to Cisplatin by Inhibiting Sonic Hedgehog Signaling
Authors: Cui Wei , Fang Tingting , Duan Zhaoheng , Xiang Dongfang , Wang Yanxia , Zhang Mengsi , Zhai Fangzheng , Cui Xiang , Yang Lang
Published: July 2020

Background: Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. Methods: Immunohistochemistry, western blotting, RT-PCR, flow cytometry and immunofluorescence microscopy were used to detect the expression of Shh pathway members and cancer stem cell(CSC) biomarkers in ESCC specimens and cell lines. Functional assays, including MTT, tumorsphere formation assay, RTCA and an in vivo tumour growth assay, were conducted to assess the effect of Dihydroartemisinin (DHA) on the proliferation and renewal ability of ESCC cells. HPLC was used to examine the concention of cisplatin in ESCC cells.Results: We found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. DHA, a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells in vitro and growth of ESCC cell-derived xenograft tumors in vivo. Conclusion: These results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.
Airway Obstruction as the Primary Manifestation of Infantile Thyroid Hemangioma: A Case Report and Literature Review
Authors: Liang Yujian , Pu Ronghui , Huang Xueqiong , Li Suping , Chen Yingqian , Tang Wen
Published: July 2020

Background: Thyroid hemangioma mostly occurs in adults and is extremely rare in infants. So far, only four pediatric cases of thyroid hemangioma have been reported, one of which has only been clinically diagnosed. Most of the reported cases are of cavernous hemangiomas; capillary hemangioma cases are very rare. To date, there are no reports on capillary thyroid hemangioma in an infant. Therefore, here we present the case of an infant with a primary capillary hemangioma of the thyroid gland, and discuss its treatment and follow-up.Case Presentation: A 2-month-old infant with normal thyroid function presented with airway obstruction as the primary manifestation of thyroid hemangioma. The main symptoms were laryngeal wheezing and dyspnea. Ultrasonography revealed hypoechoic lesions at the lower pole of the bilateral thyroid. Computed tomography revealed enlargement of the thyroid gland, inhomogeneous parenchyma enhancement, and multiple thyroid nodules. However, these imaging modalities were unable to provide an exact diagnosis and the nature of the tumor remained unknown prior to an operation. Therefore, a postoperative histopathological examination was undertaken, which revealed capillary thyroid hemangioma. The symptoms significantly improved by a combined treatment involving surgery and oral propranolol (2 mg/kg per day).Conclusion: When a well-defined capsulate mass is detected on the medical image, the possibility of primary thyroid hemangioma must be considered.
Comparison of two techniques for the treatment for atlantoaxial instability injury: C1–C2 transarticular screws and C1 lateral mass–C2 pedicle screws
Authors: Du Hoang Gia , Thanh Dao Xuan , Phuoc Vu Xuan , Hoang Nguyen Duc , Tan Le Dang , Trung Nguyen Van
Published: July 2020

The authors have requested that this preprint be removed from Research Square.
Assessment of Immunization Data Quality of Routine Reports in Ho Municipality of Volta Region, Ghana
Authors: Asem Livingstone , Ziema Sorengmen Amos
Published: July 2020

Background: Immunization has been an important public health intervention for preventing and reducing child morbidity and mortality over the years and coverage has increased in the past decades. However, the validity of the data from immunization coverages is usually disputed. Immunization data from health facilities show poor concordance between tallied registers and monthly reports as they are reported to higher levels of the health system. The study assessed the quality of data from routine immunization of some health facilities in the Ho central municipality in the Volta region of Ghana.Methods: A descriptive cross-sectional study was used to review routine immunization data in tallied registers and reports submitted to the Municipal Health Directorate (MHD) from January to December, 2015. Simple random sampling was used to select three health facilities in Ho central municipality. The Data Quality Self-assessment tool (DQS) was the main instrument used to present and analyze data for accuracy and discrepancy level between the tallied registers and reports. A template was created in Microsoft excel which automatically presented accuracy and discrepancy levels when data was entered. Ethical approval for the study was obtained from Ghana Health Service Ethics Review Committee. Results: The result showed discrepancies between recounted tallies at the facilities and reports submitted to the MHD. Accuracy ratios of 102%, 64% and 94% for Bacillus Calmette Guerin (BCG), Pentavalent (Penta) vaccine dose 3 and Measles 2 respectively indicating underreporting for BCG and over reporting for the rest were obtained. There was 460 over reported data to the municipal level representing accuracy ratio of 80% and discrepancy level of 20%. Conclusions: Immunization data was characterized by underreporting and overreporting, hence not accurate and lacked quality. Immunization data quality should be a priority among health staff at health facilities.
Unlike Morphine, Long-Term Exposure to Analgesic Mitragynine, 7-Hydroxymitragynine, Paynantheine, and Speciociliatine Alkaloids Does Not Contribute to Antinociceptive Tolerance of μ-Opioid Receptors
Authors: Elahian Fatemeh , Zahedian Sorour , Safaei Mohsen , Pahlevani-Gazi Elham , Mirzaei Seyed Abbas
Published: July 2020

Background: Opioids are the most well known antinociceptive alkaloids all over the world, but tolerance and physical dependence are their dominant concerns in clinical applications. In contrast, monoterpene alkaloids are newly considered for their roles in pain management.Methods: In this regard, the clinical safety of mitragynine, 7-hydroxymitragynine, speciociliatine, and paynantheine was determined by cytotoxicity, antioxidant, and antigenotoxicity assays. In parallel alkaloids were studied on β-arrestin-2, ERK1/2, and p-ERK1/2 transcription and translation levels during three days on SH-SY5Y cells. Results: Results confirmed alkaloid- and concentration- dependency of the cytotoxicity, antigenotoxicity, and antioxidant activity. Although morphine was recorded as the safest alkaloid here, speciociliatine and mitragynine represented around 1200- and 20- fold higher DNA protection capacity than morphine, respectively. Monoterpene alkaloids transiently made the transcript ocean turbulent, but western blot analyses have proved significant down-regulation of targeted proteins in SH-SY5Y cells during the experiment days. Conclusions: Data indicated that monoterpene alkaloid derivatives are putative analgesic agents that do not stimulate opioid receptor tolerance and suggesting that patients may benefit from their antinociceptive activities without physical dependence or tolerance concerns in future clinics.
Synergistic effect of Vitamin D Supplement and mindfulness on insulin resistance and different aspects of cognitive function in Vitamin D Deficient Type 2 Diabetic mellitus (T2DM) women: A pilot randomized clinical trial with placebo-controlled
Authors: davoudi mohammadreza , Rezaei Parnian , Ahmadi Seyyed Mojtaba , Taheri Amir Abbas
Published: July 2020

Purpose

This study aimed to examining Synergistic effect of Vitamin D (VD) Supplement and mindfulness on insulin resistance and different aspects of cognitive function in VD Deficient Type 2 Diabetic women.
Methods

In this randomized-controlled trial, totally 225 women with T2DM and VD deficiency were randomly allocated to five groups: (1) mindfulness, (2) mindfulness and VD, (3) mindfulness and placebo, (4) VD, and (5) placebo. Mindfulness includes 12 sessions and VD patients received a daily 4000 IU oral dosage (two capsules) with 28,000 IU vitamin D weekly for 12 weeks. Sun exposure, anthropometric indices, dietary intake, physical activity, energy levels, laboratory analyses, were measured at the pre-test and after 12-week supplementation. dependent variables include cognitive function (Risky decision making, IQ and Trail Making Test) and insulin resistance.
Results

In baseline, measures were not different among the groups. At the end of treatment, cognitive function results showed improvement for all groups except the “placebo” group. About other groups, there was not any difference between VD and mindfulness groups (or combinations with placebo). but in “VITAMIN + MINDFULNESS” has a greater improvement rather than other groups (P < 0.05). This result exactly repeated for insulin resistance. However, there were not any significant difference among groups for IQ(P > 0.05). There was any difference among groups for sunlight exposure and BMI (P > 0.05). For FBS only in combined group (VD + Mindfulness) the FBS significantly reduced that is synergistic effects (P < 0.05).
Conclusion

Combining VD Supplement and mindfulness can reduce insulin resistance and improve different aspects of cognitive function in VD Deficient patients.
Haemolysis in Patients with End-Stage Renal Disease Receiving Haemodialysis: A Cross-Sectional Study
Authors: Matsumura Koichiro , Okumiya Toshika , Sugiura Tetsuro , Takahashi Nobuyuki , Yamamoto Yoshihiro , Kikuchi Sanae , Fujii Kenichi , Otagaki Munemitsu , Shiojima Ichiro
Published: July 2020

Background: Haemolysis due to mechanical stress on red blood cells (RBCs) during extracorporeal circulation has been reported in patients receiving haemodialysis. However, little is known about the incidence of, and the mechanisms underlying haemolysis in patients receiving maintenance haemodialysis. We sought to investigate the incidence and underlying mechanisms of haemolysis in patients with end-stage renal disease undergoing maintenance dialysis by measuring erythrocyte creatine.Method: In a cross-sectional study, we evaluated 69 patients with end-stage renal disease receiving haemodialysis (n = 55) or peritoneal dialysis (n = 14). Erythrocyte creatine, a quantitative marker of mean RBC age, was measured with other haemolytic markers including haptoglobin, reticulocyte count and lactate dehydrogenase.Results: RBC age was significantly shorter [47.7 (43.2–52.8) days vs. 59.8 (56.0–66.2) days, p<0.0001], and haptoglobin was significantly lower in haemodialysis patients than in those with peritoneal dialysis, although haemoglobin levels were comparable in the two groups. When haemodialysis patients were stratified by median RBC age (47.7 days), patients with shortened RBC age had higher intradialytic ultrafiltration rates, larger erythropoiesis-stimulating agent doses, and a higher erythropoietin resistance index compared to that of those with preserved RBC age.Conclusions: Haemolysis exists in patients receiving maintenance haemodialysis, especially in those with greater intradialytic fluid extraction.
Single nucleotide polymorphism analysis in breast cancer using MassARRAY from Jammu and Kashmir, India
Authors: Bakshi Divya , Nagpal Ashna , Sharma Varun , Sharma Indu , Shah Ruchi , Sharma Bhanu , Bhat Amrita , Verma Sonali , Bhat Gh. Rasool , Abrol Deepak , Sharma Rahul , Vashnavi Samantha , Kumar Rakesh
Published: July 2020

BackgroundBreast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. MethodsSNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. ResultsThe SNPs were rs12190287 (TCF21) having OR 1.713 (1.08-2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136-5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123 -0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46-0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. ConclusionIt is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.
Mutational Profiles of Marker Genes of Cervical Carcinoma in Bangladeshi patients
Authors: Sharmin Shahana , Zohura Fatima Tuj , Islam Md. Sajedul , Shimonty Anika , Khan Md. Abdullah-Al-Kamran , Perveen Rehana , Sharmin Foujia , Ahsan Chowdhury Rafiqul , Islam Abul BMMK , Yasmin Mahmuda
Published: July 2020

Background: Cervical cancer is a gynecologic cancer type that develops in the cervix, accounting for 8% mortality of all female cancer patients. Infection with specific human papillomavirus (HPV) types is considered the most severe risk factor for cervical cancer. In the context of our socioeconomic conditions, an increasing burden of this disease and high mortality rate prevail in Bangladesh. Although several researches related to the epidemiology, HPV vaccination, and treatment modalities were conducted, researches on the mutation profiles of marker genes in cervical cancer in Bangladesh remain unexplored. Methods: In this study, five different genomic regions within the top three most frequently mutated genes (EGFR, KRAS and PIK3CA) in COSMIC database with a key role in the development of cervical cancers were selected to study the mutation frequency in Bangladeshi patients. In silico analysis was done in two steps: nucleotide sequence analysis and its corresponding amino acid analysis.Results: DNA from 46 cervical cancer tissue samples were extracted and amplified by PCR, using 1 set of primers designed for EGFR and 2 sets of primers designed for two different regions of both PIK3CA and KRAS gene. In total, 39 mutations were found in 28 patient samples. Eleven different mutations (23.91%), twenty-four different mutations (52.17%) and four mutations (8.7%) were found in amplified EGFR, PIK3CA and KRAS gene fragments, among which 1 (EGFR) was common in seven patient samples and 2 (PIKCA) were found in more than 1 patient. Our study shows that except for KRAS, the frequency of observed mutations in our patients is higher than those reported earlier in other parts of the world. Most of the exonic mutations were found only in the PIK3CA and EGFR genes.Conclusions: The study can be used as a basis to build a mutation database for cervical cancer in Bangladesh with the possibility of targetable oncogenic mutations. Further exploration needs to establish future diagnostics, personalized medicine decisions, and other pharmaceutical applications for specific cancer subtypes.
P2X7 Receptor Antagonist Attenuates Retinal Inflammation and Neovascularization Induced by Oxidized Low Density Lipoprotein
Authors: Yang Mingzhu , Qiu Ruiqi , Wang Weiping , Liu Jingyang , Li Ya , Zhu Qing , Lei Bo
Published: July 2020

Background: Inflammation and neovascularization are two vital pathological phases of AMD. Recent evidence indicates that blocking P2X7 receptor may relieve inflammation. Here, we investigated whether A740003, a P2X7 receptor antagonist, could prevent retinal inflammation and neovascularization induced by ox-LDL and explored the underlying mechanisms.Methods: ARPE-19 cells were pretreated with A740003 for 2 hours before ox-LDL exposure. Western Blot, ELISA and qPCR were used to detect the proteins and mRNA levels of NLRP3, Caspase-1, P2X7R, pIKBa, IKBa, angiogenic factors and inflammatory cytokines. ROS assay was performed to detect the ROS generation. C57BL/6 mice were subretinally injected with ox-LDL to induce retinal inflammation and neovascularization. A740003 was administrated intraperitoneally starting from day 3 before to day 14 after ox-LDL injection. Retinal function was assessed by dark- and light-adapted ERG. Retinal neovascularization was detected by retinal whole flat mount and immunofluorescence. Thickness of INL and ONL was measured to evaluate the retinal edema. Results: ox-LDL induced inflammatory responses and VEGF overproduction in human RPE cells and mouse retinas. However, A740003 decreased the expression of NLRP3, P2X7R, HIF-1a and VEGF in ARPE-19 cells. Inflammatory cytokines including IL-1b and IL-18 were down-regulated in A740003 treated cells. A740003 suppressed ROS generation and inhibited the phosphorylation of IKBa significantly. Whole flat mount of retinas and immunofluorescence showed that A740003 inhibited the angiogenesis induced by ox-LDL in vivo. The elevated mRNA and protein levels of NLRP3, Caspase-1, P2X7R, HIF-1a and VEGF decreased and IL-1b release was repressed in A740003 treated mice. Besides, the phosphorylation of IKBa was suppressed in the retinas of A740003 treated mice. The retinal edema was alleviated by A740003 treatment. The b- and a-wave amplitudes of ERG were remarkably preserved in A740003 treated mice. Conclusions: A740003 significantly reduced ocular inflammatory responses and VEGF production in ARPE-19 cells. In addition, the P2X7R antagonist reduced retinal inflammation, neovascularization, and protected retinal function in mice. The protective effects were associated with regulating of NLRP3 inflammasome and NF-kB pathway, suppression of ROS generation, as well as inhibition of angiogenic factors.
The Impact of Leadership Autonomy Support, Psychological Capital and Creativity on Hospital Employees’ Innovative Behaviour
Authors: Slåtten Terje , Lien Gudbrand , Mutonyi Barbara Rebecca
Published: July 2020

Background: There is growing interest in and focus on healthcare services research to identify factors associated with innovation in healthcare organizations. However, previous innovation research has concentrated primarily on the organizational level. In contrast, this study focuses on innovation by individual employees. The specific aim is to examine factors with potential impact on individual employee innovation in hospital organizations. Thus, the study significantly deepens and broadens previous research on innovation in the domain of health services.Methods: A conceptual model was developed and tested on a sample of hospital employees. Partial least-squares structural equation modelling (PLS-SEM) was used to analyse the data with Stata software. Mediation analysis was used to test the proposed indirect effects.Results: Hospital employees’ individual innovative behaviour is directly and positively associated with individual creativity (b = 0.440), psychological capital (b = 0.34) and leadership autonomy support (b = 0.07). The relationships between leadership autonomy support, psychological capital and individual innovative behaviour are all mediated by employees’ creativity. Psychological capital mediates the relationship between leadership autonomy support and individual innovative behaviour. Overall, the proposed model explains 50% of the variance in hospital employees’ innovative behaviour.Conclusions: This study reveals a complex pattern of links between innovative behaviour and leadership autonomy support, employees’ creativity and employees’ psychological capital. However, the findings indicate that leadership autonomy support has a dominant and multifaceted impact on hospital employees’ innovative behaviour.
Natural Course of Fat Necrosis After Breast Reconstruction: A 10-Year Follow-Up Study
Authors: Lee Jeeyeon , Park Ho Yong , Kim Wan Wook , Lee Jeong Ju , Keum Hee Jung , Yang Jung Dug , Lee Jeong Woo , Lee Joon Seok , Jung Jin Hyang
Published: July 2020

Background: Although fat necrosis is a minor postoperative complication after breast reconstruction, occasionally it mimics to tumor recurrence in patients with breast cancer. Therefore, the surgeon should distinguish between benign fat necrosis and true local recurrence. The authors evaluated the clinical characteristics of fat necrosis after breast reconstruction and investigated the natural course of fat necrosis.Methods: Between 2007 and 2013, a total of 362 patients underwent breast reconstruction after partial or total mastectomy for breast cancer in Kyungpook National University Hospital. Clinicopathologic characteristics and the occurrence of fat necrosis were assessed during surveillance for 10 years of mean follow-up period.Results: There were 42 cases (11.6 %) of fat necrosis after breast reconstruction with partial or total mastectomy which were confirmed by needle or excision biopsy. The fat necrosis was resolved after a mean period of 45.9 months (SD, ± 42.1) and 26 cases (61.9 %) of fat necrosis were almost completely resolved (less than 5 mm) during 10-year follow-up period.Conclusion: Based on the natural course of fat necrosis, the fat necrosis after breast reconstruction can be only monitored, if pathologic confirmation was done. More than half of the cases will be resolved within 2–3years.
LncRNA LEF1-AS1 Promotes Metastasis of Prostatic Carcinoma via the Wnt/β-Catenin Pathway
Authors: Li Weiyuan , Yang Ganggang , Yang Dengke , Li Dong , Sun Qian
Published: July 2020

Background: Long noncoding RNAs (lncRNAs), which are important functional regulators in cancer, have emerged as critical molecular regulators in various biological processes. However, the mechanisms by which LEF1-AS1 modulates Androgen-Independent Prostate Cancer (AIPC) development remain largely unknown.Methods: The LEF1-AS1 expression level was detected in tumour tissues and adjacent normal tissues of AIPC patients by using next-generation sequencing technology and qRT-PCR. Cell proliferation, migration and invasion were assessed by colony formation, EDU assays and transwell assays, respectively. Xenograft assay was conducted to determine the effect of LEF1-AS1 on cell proliferation in vivo.Results: LEF1-AS1 promoted the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and in vivo. In this mechanism, LEF1-AS1 recruited the transcription factor C-myb to the promoter region of FZD2, which activated FZD2 transcription. Moreover, LEF1-AS1 functioned as a competing endogenous RNA (ceRNA) acting as a sponge for miR-328, which activated CD44.Conclusion: Collectively, these data indicate that LEF1-AS1 is a tumour promoter in the development of AIPC and that it may contribute to the improvement of AIPC diagnosis and therapy.
Primary Bone Lymphoma of the Humerus (About A Case and Literature Review)
Authors: Yahyaoui Mounir , Aharram Soufiane , Amghar Jawad , Agoumi Omar , Daoudi Abdelkrim
Published: July 2020

Background: Primary localised bone lymphoma is a rare affection prevalent in humans. It often involves long bones, but can be found in all the skeleton bones. The diagnosis is based on the anatomopathological study with immunohistochemical study of a bone biopsy. Case presentation: We also report the first diagnosed case of primary bone lymphoma of the humerus since the inauguration of our university hospital (since September 2014).Conclusions: It is an extremely rare pathology, of which the orthopedist must know. Treatment is based on chemotherapy (with or without anti-CD20) followed by radiotherapy. The prognosis of primary localised bone lymphoma is very favorable.
A phase II randomized trial of sodium oligomannate in Alzheimer's dementia
Authors: Wang Tao , Kuang Weihong , Chen Wei , Zhang Liming , Xu Wenwei , Li Yingjie , Li Hailin , Peng Ying , Chen Yangmei , Wang Baojun , Xiao Jinsong , Li Honghua , Yan Chuanzhu , Du Yifeng , Tang Mouni , He Zhiyi , Chen Haibo , Li Wei , Lin Hong , Shi Shugui , Bi Jianzhong , Zhou Huadong , Cheng Yan , Gao Xiaoping , Guan Yihui , Huang Qiu , Chen Kewei , Xin Xianliang , Ding Jian , Geng Meiyu , Xiao Shifu
Published: July 2020

Background: Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients.Methods: The 24-week multi-center, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer's Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL and NPI at 24 weeks after treatment compared with baseline. A sub-group study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements.Results: Comparing with placebo group (n=83, change -1.45), the ADAS-Cog12 score change in GV-971 600mg group (n=76) was -1.39 (p=0.89), GV-971 900mg group (n=83) was -2.58 (p=0.30). The treatment responders according to CIBIC-plus assessment was significantly higher in GV-971 900mg group than placebo group (92.77% vs 79.52%, p<0.05). GV-971 900mg subgroup showed a significantly lower cerebral metabolic rate for glucose decline than the placebo subgroup at the left precuneus, right posterior cingulate, and right hippocampus. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%.Conclusions: GV-971 was safe and well tolerated. GV-971 900mg was chosen for phase III clinical study.Trial registration: ClinicalTrials.gov, NCT01453569. Registered 18 October, 2011, https://clinicaltrials.gov/ct2/show/NCT01453569?term=NCT01453569&draw=2&rank=1.
Mental health impacts among health workers during COVID-19 in a low resource setting: a cross-sectional survey from Nepal
Authors: Khanal Pratik , Devkota Navin , Dahal Minakshi , Paudel Kiran , Joshi Devavrat
Published: July 2020

Background: Health care workers exposed to COVID-19 might be at risk of developing mental health problems. The study aimed to identify factors associated with anxiety, depression and insomnia among health workers involved in COVID-19 response in Nepal. Methods: This was a cross-sectional web-based survey conducted in between April 26 to May 12, 2020. A total of 475 health workers participated in the study. Anxiety and depression were measured using 14-item Hospital Anxiety and Depression Scale (HADS: 0- 21) and insomnia was measured by using 7-item Insomnia Severity Index (ISI: 0-28). Multivariable logistic regression analysis was done to determine the risk factors of mental health outcomes. Results: Overall, 41.9% of health workers had symptoms of anxiety, 37.5% had depression symptoms and 33.9% had symptoms of insomnia. Stigma faced by health workers was significantly associated with higher odds of experiencing symptoms of anxiety (AOR: 2.47; 95% CI: 1.62-3.76), depression (AOR: 2.05; 95% CI: 1.34-3.11) and insomnia (AOR: 2.37; 95% CI: 1.46-3.84). History of medication for mental health problems was significantly associated with higher likelihood of experiencing symptoms of anxiety (AOR: 3.40; 95% CI:1.31-8.81) , depression (AOR: 3.83; 95% CI: 1.45-10.14) and insomnia (AOR: 3.82; 95% CI: 1.52-9.62) while inadequate precautionary measures in the workplace was significantly associated with higher odds of exhibiting symptoms of anxiety (AOR: 1.89; 95% CI: 1.12-3.19) and depression (AOR: 1.97; 95% CI: 1.16-3.37). Nurses (AOR: 2.33; 95% CI: 1.21-4.47) were significantly more likely to experience anxiety symptoms than other health workers. Conclusion: The study findings revealed higher proportion of anxiety, depression and insomnia among health workers during the early phase of the pandemic in Nepal. Health workers facing stigma, those with history of medication for mental health problem, and those reporting to having inadequate precautionary measures in their workplace were more at risk of developing mental health outcomes. A focus on improving mental health wellbeing of health workers should be immediately initiated with attention to reduction of stigma, ensuring adequate support system such as personal protective equipments, and family support for those with history of mental health problems.