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Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations.In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns.As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs.We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

In the absence of clear pathologic differences, clinical history may differentiate potential primary parotid squamous cell carcinomas (SCC) from metastases. The presence of an ultraviolet (UV) signature can distinguish between tumors of cutaneous and non-cutaneous origin. This study aimed to investigate rates of UV signature mutations in squamous cell carcinomas of the parotid gland as well as differences in clinical features between tumors of cutaneous and non-cutaneous origin. Clinical and pathologic data were collected from 71 patients with SCC involving the parotid gland, of which 48 had cutaneous, 10 had mucosal, and 13 had no history of SCC. In 34 available cases, genomic DNA was isolated from formalin-fixed paraffin-embedded tissue specimens and sequenced using a targeted hybrid capture 1213 gene panel. Tumor mutational burden and COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signatures were calculated. Most (74%) were UV-positive. Patients with UV-positive tumors were significantly older, white, and had higher rates of sun exposure. Patients with UV-negative tumors had a significantly higher mortality rate and shorter time to death: 6 (67%) died of disease with a median time to death of 9 months compared to 5 (20%) UV-positive patients who died of disease with a median time to death of 32 months. Pathologic features did not significantly vary by clinical history or UV status. The presence of a UV-signature combined with clinical history can be used to determine the primary source of SCC involving the parotid gland. UV-positivity may reflect a less aggressive disease course in an older population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12105-021-01349-x.

Background Rosai-Dorfman disease (RDD) is a rare benign proliferative disease whose etiology is not clear and may be related to infection or unexplained immune dysfunction. The authors present a case of RDD with lung involvement in a 10-year-old patient. Case summary A 10-year-old girl found that her left cervical lymph nodes were enlarged for more than 7 mo, and the largest range was about 6.5 cm × 5.9 cm × 8.1 cm. Cervical magnetic resonance imaging showed multiple masses in the left neck, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. A malignant tumor, with a high possibility of lymph node metastasis, was initially considered. At the same time, lung computed tomography showed multiple nodules of different sizes scattered on both sides of the lung, with uniform internal density. Thus, a possible metastatic tumor was considered. Finally, RDD was diagnosed by pathology and immunohistochemistry. According to the antibiogram, clindamycin was administered for 2 wk, and prednisone acetate was administered for 7 wk. Nine months later, the ulcer in the left neck was better than before, but the imaging showed that the lesion was not controlled. Conclusion The diagnosis of RDD cannot be made by a single tool and its treatment is a long-term exploratory process. Follow-up is necessary.

Background : Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. Methods : Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). Results : Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. Limitations : Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. Conclusions : Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

This review is aimed to provide a comprehensive overview of the physicochemical properties and extraction processes of red palm oil, its nutritional properties and applications in food. Crude palm oil is firstly extracted from the fruit mesocarp and processed into red palm oil using pre-treatment of crude palm oil, with deacidification steps, and deodorization via short-path distillation. These processes help to retain β-carotene and vitamin E in red palm oil. Palmitic, stearic and myristic acids are the saturated fatty acids in red palm oil, while the unsaturated fatty acids are oleic, linoleic and linolenic acids. It is reported to overcome vitamin A deficiency, promote heart health and have anti-cancer properties.

Long non-coding RNAs (lncRNAs) act as tumor suppressors or oncogenes in tumor development and progression. In this study, we explored the expression and biological role of lncRNA NRON in gastric cancer (GC). We observed that lncNRON was upregulated in GC tissues and cell lines, and high lncNRON expression was associated with malignant features and poor prognosis in GC patients. LncNRON was found to promote the proliferation and tumorigenicity of GC cells. Mechanistically, lncNRON exerted its oncogenic functions by binding to the N6-methyladenosine eraser ALKHB5 and mediating Nanog mRNA decay. In conclusion, our results suggest that lncNRON serves as an oncogenic lncRNA in GC and thus may be a promising prognostic factor and potential therapeutic target for GC patients.

Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on angiography (stenosis 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA.A total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR-). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%-75% of peak heart rate) on a bicycle or treadmill.After one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR- group (P 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P 0.05) and MACE (log-rank P 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.483; 95% confidence interval [CI], 0.279-0.818; P 0.01) and MACE (HR = 0.574; 95% CI, 0.403-0.827; P 0.001).A long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.

Injury to the vagus nerve has been proposed to be associated with occurrence of gallstones after gastrectomy. We investigated the effect of preservation of hepatic branch of the vagus nerve on prevention of gallstones during laparoscopic distal (LDG) and pylorus-preserving gastrectomy (LPPG). Preservation of the vagus nerve was reviewed of cT1N0M0 gastric cancer patients underwent LDG (n = 323) and LPPG (n = 144) during 2016–2017. Presence of gallstones was evaluated by ultrasonography (US) and computed tomography (CT). Incidences of gallstones were compared between the nerve preserved (h-DG, h-PPG) group and sacrificed (s-DG, s-PPG) group. Clinicopathological features were also compared. The 3-year cumulative incidence of gallstones was lower in the h-DG (2.7%, n = 85) than the s-DG (14.6%, n = 238) (p = 0.017) and lower in the h-PPG (1.6%, n = 123) than the s-PPG (12.9%, n = 21) (p = 0.004). Overall postoperative complication rate was similar between the h-DG and s-DG (p = 0.861) as well as between the h-PPG and s-PPG (p = 0.768). The number of retrieved lymph nodes station #1 and 3-year recurrence-free survival were not significantly different between the preserved group and sacrificed group. Injury to the vagus nerve (p = 0.001) and high body mass index (BMI) (≥ 27.5 kg/m2) (p = 0.040) were found to be independent risk factors of gallstone formation in multivariate analysis. Preservation of hepatic branch of the vagus nerve can be recommended for LDG as well as LPPG of early gastric cancer patients to reduce postoperative gallstone formation.

Background Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) accounts for approximately 5% ‐ 6% of acute myocardial infarction (AMI) patients. Anxiety symptoms are common in patients with coronary artery disease (CAD), and are associated with a poor prognosis. However, the association between anxiety and MINOCA outcomes is less clear. Hypothesis Anxiety will be associated with clinical outcomes in patients with MINOCA. Methods and Results Between November 2014 and December 2016, 620 hospitalized patients with MINOCA were recruited from a single center. Within 7 days of coronary angiography, anxiety was assessed using the Zung Self‐Rating Anxiety Scale. The primary endpoint was all‐cause mortality; secondary endpoint was any major adverse cardiovascular event (MACE). After 3 years, 87 deaths and 151 MACE had occurred. Kaplan‐Meier curves indicated the unadjusted rates of all‐cause mortality (log‐rank P = .045) and MACE (log‐rank P = .023) were significantly higher in the anxiety group compared with the control group of patients without anxiety. Multivariate Cox regression analysis showed that clinically significant anxiety was an independent prognostic factor for all‐cause mortality as well as MACE (hazard ratio [HR] = 1.547; 95% confidence interval [CI], 1.006‐2.380; P = .047; HR = 1.460; 95% CI, 1.049‐2.031; P = .025; respectively). Conclusions Anxiety is significantly and independently associated with an increased risk of all‐cause mortality and MACE in patients with MINOCA.

An Ir8Pd4-heteronuclear metal-organic cage (MOC-51) was assembled from bipodal metalloligand [Ir(ppy)2(qpy)(BF4)] (qpy = 4,4′:2′,2″:4″,4‴-quaterpyridine; ppy = 2-phenylpridine) with Pd(II) salt. The cubic barrel shaped MOC shows one-photon and two-photon excited deep-red emission, as well as large singlet oxygen quantum yields under visible light irradiation, therefore exhibiting great potentials in organelles-targeted cell imaging and photodynamic therapy (PDT). Compared with the Ir(III) metalloligand, the Ir8Pd4-MOC showed less dark toxicity and higher mitochondria-targeting efficiency. The localization in mitochondria overcomes the limitation of short lifetime and diffusion distance of ROS in cell, thus improved PDT effect can be obtained in low light dose usage of the MOC. This study presents the first case of Ir-based metal-organic cages for bio-applications in successful integration of imaging diagnosis and photodynamic therapy

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Background Circular RNAs (circRNAs) as a novel subgroup of non-coding RNAs act a critical role in the pathogenesis of gastric cancer (GC). However, the underlying mechanisms by which hsa_circ_0003855 (circDUSP16) contributes to GC are still undocumented. Materials The differentially expressed circRNAs were identified by GEO database. The association of circDUSP16 or miR-145-5p expression with clinicopathological features and prognosis in GC patients was analyzed by FISH and TCGA-seq data set. Loss- and gain-of-function experiments as well as a xenograft tumor model were performed to assess the role of circDUSP16 in GC cells. circDUSP16-specific binding with miR-145-5p was confirmed by bioinformatic analysis, luciferase reporter, and RNA immunoprecipitation assays. Results The expression levels of circDUSP16 were markedly increased in GC tissue samples and acted as an independent prognostic factor of poor survival in patients with GC. Knockdown of circDUSP16 repressed the cell viability, colony formation, and invasive potential in vitro and in vivo, but ectopic expression of circDUSP16 reversed these effects. Moreover, circDUSP16 possessed a co-localization with miR-145-5p in the cytoplasm, and acted as a sponge of miR-145-5p, which attenuated circDUSP16-induced tumor-promoting effects and IVNS1ABP expression in GC cells. MiR-145-5p had a negative correlation with circDUSP16 expression and its low expression was associated with poor survival in GC patients. Conclusions CircDUSP16 facilitates the tumorigenesis and invasion of GC cells by sponging miR-145-5p, and may provide a novel therapeutic target for GC.

Background: Among the nursing aides employed at long-term care facilities (LTCFs), those with musculoskeletal disorders (MSDs) are most likely to experience disability or develop an intention to leave. The purpose of this study was to investigate the association of work-related psychological factors among nursing aides in LTCFs with MSDs in Taiwan. Methods: Purposive sampling was used in this cross-sectional study to enrol 308 nursing aides from residential LTCFs in Taiwan as research subjects. A demographic and job background survey, a job content questionnaire (JCQ), and the Nordic musculoskeletal questionnaire (NMQ) were used to collect data. Results: Lower job control associated with higher psychological job demands, and lower social support was associated with more severe MSDs for the nursing aides (p < 0.001). Among the MSDs reported by nursing aides in LTCFs, lower back pain was the most serious. In addition, nationality, age, exercise habits, chronic diseases, worksite, lack of rest time, lack of assistive devices, low coworker support, and high psychological job demands were significant factors affecting MSDs. In total, 42.1% of the variance in MSDs among nursing aides in LTCFs was explained. Conclusions: Work-related psychological factors among nursing aides in LTCFs have an important association with MSDs. For nursing aides, coworker support should be improved, and their psychological demands at work should be reduced.

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period.Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids.Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was −7.0 [0.6] kg vs. −6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was −7 [0.7] mmHg vs. −7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was −6 [0.5] mmHg vs. −5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial.Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension.Clinical Trial Registration:http://www.chictr.org.cn, identifier: ChiCTR2000040468.

Background Using indocyanine green (ICG) fluorescence imaging and tissue marking dyes (TMDs), perigastric lymphatic mapping and their pathological correlation were examined to see whether ICG staining covers all metastatic lymph nodes (LNs) in advanced gastric cancer (AGC). Methods Patients with AGC who underwent open distal or total gastrectomy were enrolled. ICG was serially injected intraoperatively into the subserosa along the greater and lesser curvatures. Stomach specimens were examined under a near-infrared camera. ICG-stained LNs were named, excised, and tattooed with different colored TMDs to retrace the exact location after pathological examinations. Results A total of 687 LNs and 69 LN stations were examined from 11 patients. The map of the perigastric lymphatic network showing the topography of ICG-stained and ICG-unstained LNs, including metastatic information, was successfully reconstructed. The average number of ICG-stained and ICG-unstained LNs were 23.6 ± 12.3 (37.8%) and 38.8 ± 17.1 (62.2%), respectively. LN metastases were present in 28 LN stations of 8 patients. Of 8 cases with LN metastases, 40% (11.1–75% per case) of metastatic LNs were stained by ICG. Of 28 metastatic LN stations, 21 (75.0%) were covered by ICG, and actual metastatic LNs were stained in 16 LN stations (57.1%). In 4/8 cases (50%), all metastatic LN stations showed ICG signals. Conclusions ICG fluorescence imaging and TMD are useful tools for visualizing the perigastric lymphatic network and retracing the exact location of ICG-stained LNs in AGC. However, ICG imaging is still not recommended for selective LN dissection in AGC because of the limited staining of perigastric LNs.

The maintenance of constant karyoplasmic ratios suggests that nuclear size has physiological significance. Nuclear size anomalies have been linked to malignant transformation, although the mechanism remains unclear. By expressing dominant-negative TER94 mutants in Drosophila photoreceptors, here we show disruption of VCP (valosin-containing protein, human TER94 ortholog), a ubiquitin-dependent segregase, causes progressive nuclear size increase. Loss of VCP function leads to accumulations of MDC1 (mediator of DNA damage checkpoint protein 1), connecting DNA damage or associated responses to enlarged nuclei. TER94 can interact with MDC1 and decreases MDC1 levels, suggesting that MDC1 is a VCP substrate. Our evidence indicates that MDC1 accumulation stabilizes p53A, leading to TER94K2A-associated nuclear size increase. Together with a previous report that p53A disrupts autophagic flux, we propose that the stabilization of p53A in TER94K2A-expressing cells likely hinders the removal of nuclear content, resulting in aberrant nuclear size increase., Cells maintain a constant cytoplasm to nucleus volume ratio, although the role of DNA damage is not well explored. Here, the authors use Drosophila to connect TER94, the fly homolog of VCP, to disruption of DNA damage repair, leading to ubiquitinated Mu2 protein accumulation and enlarged nuclei.

Background Hypertrophic cardiomyopathy (HCM) is considered to be the most common cause of sudden death in young people and is associated with an elevated risk of mood disorders. Depression has emerged as a critical risk factor for development and progression of coronary artery disease; however, the association between depression and HCM outcomes is less clear. We sought to examine the impact of depression on clinical outcomes in patients with HCM. Methods and Results Between January 2014 and December 2017, 820 patients with HCM were recruited and followed for an average of 4.2 years. End points were defined as sudden cardiac death (SCD) events and HCM‐related heart failure events. A Chinese version of the Structured Clinical Interview followed the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and was used to diagnose depression. During the follow‐up period, SCD events occurred in 75 individuals (21.8 per 1000 person‐years), and HCM‐related heart failure events developed in 149 individuals (43.3 per 1000 person‐years). Kaplan–Meier cumulative incidence curves showed a significant association of depression disorders with SCD events (log‐rank P =0.001) and HCM‐related heart failure events (log‐rank P =0.005). A multivariate Cox regression analysis indicated that depression was an independent predictor of SCD events and HCM‐related heart failure events (41.9 versus 21.7 per 1000 person‐years; adjusted hazard ratio [HR], 1.9; 95% CI, 1.6–2.3; P P Conclusions Depression is common among patients with HCM. The diagnosis of depression is significantly and independently associated with an increased risk of SCD events and heart failure events in patients with HCM.

Background Pancreatic ductal adenocarcinoma (PDAC) is a leading causes of cancer mortality worldwide. Currently, laparoscopic pancreatic resection (LPR) is extensively applied to treat benign and low-grade diseases related to the pancreas. The viability and safety of LPR for PDAC needs to be understood better. Laparoscopic distal pancreatectomy (LDP) and pancreaticoduodenectomy (LPD) are the two main surgical approaches for PDAC. We performed separate propensity score matching (PSM) analyses to assess the surgical and oncological outcomes of LPR for PDAC by comparing LDP with open distal pancreatectomy (ODP) as well as LPD with open pancreaticoduodenectomy (OPD). Methods We assessed the data of patients who underwent distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for PDAC between January 2004 and February 2020 at our hospital. A one-to-one PSM was applied to prevent selection bias by accounting for factors such as age, sex, body mass index, and tumour size. The DP group included 86 LDP patients and 86 ODP patients, whereas the PD group included 101 LPD patients and 101 OPD patients. Baseline characteristics, intraoperative effects, postoperative recovery, and survival outcomes were compared. Results Compared to ODP, LDP was associated with shorter operative time, lesser blood loss, and similar overall morbidity. Of the 101 patients who underwent LPD, 10 patients (9.9%) required conversion to laparotomy. The short-term surgical advantage of LPD is not as apparent as that of LDP due to conversions. Compared with OPD, LPD was associated with longer operative time, lesser blood loss, and similar overall morbidity. For oncological and survival outcomes, there were no significant differences in tumour size, R0 resection rate, and tumour stage in both the DP and PD subgroups. However, laparoscopic procedures appear to have an advantage over open surgery in terms of retrieved lymph nodes (DP subgroup: 14.4 ± 5.2 vs. 11.7 ± 5.1, p = 0.03; PD subgroup 21.9 ± 6.6 vs. 18.9 ± 5.4, p = 0.07). These two groups did not show a significant difference in the pattern of recurrence and overall survival rate. Conclusions Laparoscopic DP and PD are feasible and oncologically safe procedures for PDAC, with similar postoperative outcomes and long-term survival among patients who underwent open surgery.

Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment.

Significance Functional connectivity within the default mode network in patients with major depressive disorder has been frequently reported to be abnormal but with contradicting directions in previous studies with small sample sizes. In creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments., Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Purpose: Everolimus inhibits the mTOR, activating cytoprotective autophagy. Hydroxychloroquine inhibits autophagy. On the basis of preclinical data demonstrating synergistic cytotoxicity when mTOR inhibitors are combined with an autophagy inhibitor, we launched a clinical trial of combined everolimus and hydroxychloroquine, to determine its safety and activity in patients with clear-cell renal cell carcinoma (ccRCC). Patients and Methods: Three centers conducted a phase I/II trial of everolimus 10 mg daily and hydroxychloroquine in patients with advanced ccRCC. The objectives were to determine the MTD of hydroxychloroquine with daily everolimus, and to estimate the rate of 6-month progression-free survival (PFS) in patients with ccRCC receiving everolimus/hydroxychloroquine after 1–3 prior treatment regimens. Correlative studies to identify patient subpopulations that achieved the most benefit included population pharmacokinetics, measurement of autophagosomes by electron microscopy, and next-generation tumor sequencing. Results: No dose-limiting toxicity was observed in the phase I trial. The recommended phase II dose of hydroxychloroquine 600 mg twice daily with everolimus was identified. Disease control [stable disease + partial response (PR)] occurred in 22 of 33 (67%) evaluable patients. PR was observed in 2 of 33 patients (6%). PFS ≥ 6 months was achieved in 15 of 33 (45%) of patients who achieved disease control. Conclusions: Combined hydroxychloroquine 600 mg twice daily with 10 mg daily everolimus was tolerable. The primary endpoint of >40% 6-month PFS rate was met. Hydroxychloroquine is a tolerable autophagy inhibitor in future RCC or other trials.

Long non-coding RNAs (lncRNAs) act as tumor suppressors or oncogenes in tumor development and progression. In the present study, we explored the expression and biological role of the lncRNA DNM3OS in gastric cancer (GC). We observed that DNM3OS was upregulated in GC tissues and cell lines, and high DNM3OS expression was correlated with malignant features and served as an indicator of a poor prognosis for GC patients. DNM3OS knockdown inhibited the proliferation of GC cells, and reduced DNM3OS suppressed tumor growth in vivo. Moreover, DNM3OS depletion inhibited the migration and invasion of GC cells through the suppression of the Snail-mediated epithelial-mesenchymal transition (EMT). In conclusion, we demonstrated that DNM3OS serves as an oncogenic lncRNA in GC, and we implicated DNM3OS as a promising prognostic factor and a potential therapeutic target for GC patients.

The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.

Highlights • Two subtypes with distinct default mode network profiles exist in major depression. • Subtypes of major depression are robust in validation datasets across brain atlases. • Hyper- & hypo-connectivity DMN subgroups have comparable clinical symptom variables. • Future studies should examine whether two subtypes have differing treatment response., Background Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. Methods The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. Results Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. Conclusions Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

RgC4H promotes phenolic accumulation in R. glutinosa, activating the molecular networks of its antioxidant systems, and enhancing the tolerance to oxidative stresses exposed to drought, salinity and H2O2 conditions. Rehmannia glutinosa is of great economic importance in China and increasing R. glutinosa productivity relies, in part, on understanding its tolerance to oxidative stress. Oxidative stress is a key influencing factor for crop productivity in plants exposed to harsh conditions. In the defense mechanisms of plants against stress, phenolics serve an important antioxidant function. Cinnamate 4-hydroxylase (C4H) is the first hydroxylase in the plant phenolics biosynthesis pathway, and elucidating the molecular characteristics of this gene in R. glutinosa is essential for understanding the effect of tolerance to oxidative stress tolerance on improving yield. Using in vitro and in silico methods, a C4H gene, RgC4H, from R. glutinosa was isolated and characterized. RgC4H has 86.34–93.89% amino acid sequence identity with the equivalent protein in other plants and localized to the endoplasmic reticulum. An association between the RgC4H expression and total phenolics content observed in non-transgenic and transgenic R. glutinosa plants suggests that this gene is involved in the process of phenolics biosynthesis. Furthermore, the tolerance of R. glutinosa to drought, salinity and H2O2 stresses was positively or negatively altered in plants with the overexpression or knockdown of RgC4H, respectively, as indicated by the analysis in some antioxidant physiological and molecular indices. Our study highlights the important role of RgC4H in the phenolics/phenylpropanoid pathway and reveals the involvement of phenolic-mediated regulation in oxidative stress tolerance in R. glutinosa.

Opioid abuse alters the functions of immune cells in both in vitro and in vivo systems, including macrophages. Here, we investigated the effects of methadone, a widely used opioid receptor agonist for treatment of opiate addiction, on the expression of intracellular viral restriction factors and HIV replication in primary human macrophages. We showed that methadone enhanced the HIV infectivity in primary human macrophages. Mechanistically, methadone treatment of macrophages reduced the expression of interferons (IFN-β and IFN-λ2) and the IFN-stimulated anti-HIV genes (APOBEC3F/G and MxB). In addition, methadone-treated macrophages showed lower levels of several anti-HIV microRNAs (miRNA-28, miR-125b, miR-150, and miR-155) compared to untreated cells. Exogenous IFN-β treatment restored the methadone-induced reduction in the expression of the above genes. These effects of methadone on HIV and the antiviral factors were antagonized by pretreatment of cells with naltrexone. These findings provide additional evidence to support further studies on the role of opiates, including methadone, in the immunopathogenesis of HIV disease.

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5–10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA.Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke.Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan–Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286–2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201–2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications.Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality worldwide. Total laparoscopic pancreaticoduodenectomy (TLPD) have been used in the treatment of benign and low-grade diseases on the pancreatic head. It is necessary to expand the current knowledge on the feasibility and safety of TLPD for PDAC treatment. We aimed to assess the surgical and oncological outcomes of TLPD for patients with PDAC by comparing them with open pancreaticoduodenectomy (OPD). Methods Data regarding patients who underwent pancreaticoduodenectomy for PDAC treatment from January 2013 to January 2019 in our hospital were obtained. Baseline characteristics, intraoperative effects, postoperative recoveries, and survival outcomes were compared. To overcome selection bias, we performed a 1:1 match using propensity score matching (PSM) between TLPD and OPD. We also conducted a systematic review and meta-analysis. Results The original cohort included 276 patients (TLPD; 98 patients, OPD; 178 patients). After PSM, there were 89 patients in each group and the patient demographics were well matched. Of the 98 patients who underwent TLPD, 8 (8.2%) required conversions to laparotomies. Compared to OPD, TLPD could be performed with longer operative times, had less blood loss, and had lower overall morbidities. Regarding oncological and survival outcomes, there were no significant differences in tumor size, R0 resection rates and tumor stages between groups. However, TLPD had an advantage over OPD in terms of retrieved lymph nodes (21.9 ± 6.6 vs. 18.9 ± 5.4, p < 0.01). There were no statistically significant differences between the groups in recurrence patterns, and the 3-year recurrence-free and overall survival rates were comparable between the two groups. Meta-analysis further confirmed that the TLPD were associated with longer operative times, less blood loss, shorter hospitalizations, lower morbidities, and a greater number of retrieved lymph nodes. Conclusions TLPD are feasible and oncologically safe procedures for PDAC treatments. Postoperative outcomes and long-term survival after TLPD are superior, or not inferior, to OPD, and could be a promising alternative to open surgery for PDAC treatments. Our findings should be further evaluated by multicenter or randomized controlled trials.

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10−3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Laparoscopic distal pancreatectomy (LDP) for benign and low-grade malignant pancreatic diseases has been increasingly utilized. However, the use of LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial and has not been widely accepted. In this study, the outcomes of LDP versus conventional open distal pancreatectomy (ODP) for left-sided PDAC were examined. A retrospective review of patients who underwent LDP or ODP for left-sided PDAC between January 2010 and January 2019 was conducted. One-to-one propensity score matching (PSM) was used to minimize selection biases by balancing factors including age, sex, ASA grade, tumor size, and combined resection. Demographic data, their pathological and short-term clinical parameters, and long-term oncological outcomes were compared between the LDP and ODP groups. A total of 197 patients with PDAC were enrolled. There were 115 (58.4%) patients in the LDP group and 82 (41.6%) patients in the ODP group. After 1:1 PSM, 66 well-matched patients in each group were evaluated. The LDP group had lesser blood loss (195 vs. 210 mL, p

Context.—Proposed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs), formerly noninvasive encapsulated papillary carcinoma, follicular variant (PTC-FV), is an indolent tumor with follicular growth and frequent RAS mutations.Objective.—To detect histologic and molecular differences separating NIFTP from follicular adenomas (FAs) and invasive carcinomas, particularly papillary carcinomas with extensive follicular growth (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV).Design.—Sixty-one tumors were reviewed histologically and reclassified into 32 NIFTPs (52%), 4 IE-PTC-FVs (7%), 14 PTC-EFGs (23%), and 11 FAs (18%). Next-generation sequencing for mutations in 50 genes was performed. Clinical outcomes were recorded.Results.—The NIFTPs and FAs were well circumscribed and unencapsulated. The FAs had bland nuclei, whereas the NIFTPs showed at least 2 of 3 (67%; sufficient) nuclear features (enlargement, irregular contours, chromatin clearing). The IE-PTC-FVs had follicular growth, sufficient nuclear features, and extensive capsular invasion. The PTC-EFGs had a median of 5% papillae with intrathyroidal invasion (broad-based, sclerotic, or small follicle growth patterns); intranuclear pseudoinclusions were present only in PTC-EFGs (9 of 14; 64%). Mutations included RAS in 20 of the 32 NIFTPs (62%), 4 of the 11 FAs (36%), and 3 of the 4 IE-PTC-FVs (75%); BRAF K601E in 1 NIFTP (3%); BRAF V600E in 5 PTC-EFGs (36%). No NIFTPs or FAs recurred or metastasized. All 4 IE-PTC-FVs (100%) had hematogenous metastasis. Two PTC-EFGs (14%) had lymphatic metastasis.Conclusions.—The morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports the genetic similarity of those follicular neoplasms in contrast to the unique presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria supported by molecular testing, tumors with extensive follicular growth can be classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus papillary type or BRAF V600E–like (PTC-EFG).

Acute pulmonary embolism (PE) is one of the serious complications with high mortality after thoracic surgery. The authors aimed to determine the prevalence of PE events and evaluate additional risk factors for PE in patients with lung cancer surgery. Patients underwent lung cancer resections during January 2012 to July 2015 and had 30-day postoperative follow-up were included. Those with incomplete or miscoded data were excluded. The number of postoperative PE events was recorded retrospectively. Analyses were used to evaluate risk factors of PE during the hospitalization. The authors reviewed 11,474 patients who underwent surgery for lung cancer. The overall 30-day incidence of PE after thoracic surgery at their institution was 0.53%. The 30-day PE incidence without chemical prophylaxis was 0.57% (55/9,726) and the mortality rate was 10%. Multivariate analyses revealed that age over 66 (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05–1.12, p

While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure.Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms.There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P 0.01, voxel-P 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P 0.01, voxel-P 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P 0.01, voxel-P 0.001). While these changed brain areas had significantly association with GI symptoms (P 0.001), they were not correlated with depressive symptoms (P 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe.MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Whitmania pigra Whitman (leech, also called Shuizhi in China, abbreviated as SZ), which has been used as a traditional Chinese medicine in the treatment of blood stasis syndrome (BSS) for a long time, is vulnerable to lead pollution in aquaculture environments. SZ has good anticoagulant activity. However, there are few studies on the influence of lead pollution on it. Therefore, we carried out the following researches to explore the influence of lead pollution on the anticoagulant activity of SZ and its mechanism. Firstly, the acute blood stasis model of rats was established by subcutaneous injection of adrenaline hydrochloride and ice water bath. Then unpolluted SZ (UPS) and lead-polluted SZ (LPS) were extracted. Next, the blood stasis model rats were administrated by gavage and the rats in normal control (NC) group and blood stasis model (BM) group were given the same amount of normal saline. Finally, the blood of the rats was collected to detect the coagulation function and hemorheology indexes. The metabolomics of rat plasma was studied by ultra-high-performance liquid chromatography coupled with orbitrap mass spectrometry (UPLC-Orbitrap-MS) technology. Principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and Hierarchical clustering analysis (HCA) were used to perform metabolomics analysis. MetPA analysis was used to search for related metabolic pathways. The results of coagulation function and hemorheology showed that lead pollution could decrease the anticoagulant activity of SZ. The OPLS-DA score plots indicated that the plasma metabolites of rats in LPS group were close to BM group, while UPS group tended to be close to NC group both in the positive and negative ion mode. Hierarchical cluster analysis (HCA) suggested that UPS group and NC group were clustered into a branch, while LPS group and BM group were clustered into a branch. To sum up, lead pollution will reduce the anticoagulant activity of SZ. And lead pollution reduces the anticoagulant activity of SZ probably by influencing the metabolic pathways such as sphingolipid metabolism, amino acid metabolism and energy metabolism in rats.

// Xiao-Wu Xu 1, * , Bo-An Zheng 2, * , Zhi-Ming Hu 3 , Zhen-Yuan Qian 1 , Chao-Jie Huang 1 , Xi-Qiang Liu 3 and Wei-Ding Wu 3 1 Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Key Laboratory of Gastroenterology of Zhejiang Provincial People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China 2 Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China 3 Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, 310014, Zhejiang, China * These authors have contributed equally to this work Correspondence to: Wei-Ding Wu, email: Weidingwu@126.com Xi-Qiang Liu, email: 2583749877@qq.com Keywords: circular RNA, hsa_circ_000984, colon cancer, growth, miR-106b Received: June 05, 2017 Accepted: July 30, 2017 Published: October 10, 2017 ABSTRACT Circular RNAs (circRNAs) as a novel type of noncoding RNAs (ncRNAs) are widely studied in the development of human various diseases, including cancer. Here, we found circular RNA hsa_circ_000984 encoded by the CDK6 gene was remarkably upregulated in the tissues of colorectal cancer (CRC) patients and in the CRC cell lines. Moreover, high expression level of hsa_circ_000984 was significantly associated with advanced colorectal cancer. Further analysis revealed that hsa_circ_000984 knockdown could inhibit cell proliferation, migration, invasion in vitro and tumor formation in vivo in CRC cell lines. Mechanically, we found that hsa_circ_000984 may act as a competing endogenous RNA (ceRNA) by competitively binding miR-106b and effectively upregulate the expression of CDK6 , thereby inducing a series of malignant phenotypes of tumor cells. Taken together, these observations suggest that the hsa_circ_000984 could mediate the expression of gene CDK6 by acting as a ceRNA, which may contribute to a better understanding of between the regulatory miRNA network and CRC pathogenesis.

Objective To investigate serine protease inhibitor Kazal type 1(SPINK1) expression and its influence on the prognosis of human hepatocellular carcinoma(HCC) and to explore the underlying molecular mechanisms involved. Methods Eighty patients with HCC who underwent curative resection were followed-up with a median observation time of 58.6 months.SPINK1expression was detected in the primary HCC samples by immunohistochemistry . Its role in tumor invasion and metastasis was evaluated in vitro by gene silence using siRNA-mediated approach, rSPINK1 and U0126(an inhibitor of MEK/ERK). The proteins in the MEK/ERK signaling pathway were detected by Western blotting. Results Patients expressing high levels of SPINK1showed poor overall survival (P

Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.