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Objective: To assess the risk factors affecting development of non-tumor- related anastomotic stenosis after rectal cancer and to construct a nomogram prediction model. Methods: This was a retrospective study of data of patients who had undergone excision with one-stage intestinal anastomosis for rectal cancer between January 2003 and September 2018 in Nanfang Hospital of Southern Medical University. The exclusion criteria were as follows: (1) pathological examination of the operative specimen revealed residual tumor on the incision margin of the anastomosis; (2) pathological examination of postoperative colonoscopy specimens revealed tumor recurrence at the anastomotic stenosis, or postoperative imaging evaluation and tumor marker monitoring indicated tumor recurrence; (3) follow-up time <3 months; and (4) simultaneous multiple primary cancers. Univariate analysis using the χ 2 or Fisher's exact test was performed to assess the study patients' baseline characteristics and variables such as tumor-related factors and surgical approach ( P <0.05). Multivariate analysis using binary logistic regression was then performed to identify independent risk factors for development of non-tumor-related anastomotic stenosis after rectal cancer. Finally, a nomogram model for predicting non-tumor-related anastomotic stenosis after rectal cancer surgery was constructed using R software. The reliability and accuracy of this prediction model was evaluated using internal validation and calculation of the area under the curve of the model's receiver characteristic curve (ROC). Results: The study cohort comprised 1,610 patients, including 1,008 men and 602 women of median age 59 (50, 67) years and median body mass index 22.4 (20.2, 24.5) kg/m². Non-tumor-related anastomotic stenosis developed in 121 (7.5%) of these patients. The incidence of non-tumor-related anastomotic stenosis in patients who had undergone neoadjuvant chemotherapy, neoadjuvant radiotherapy, and surgery alone was 11.2% (10/89), 26.4% (47/178), and 4.8% (64/1,343), respectively. Neoadjuvant treatment (neoadjuvant chemotherapy: OR=2.455, 95%CI: 1.148-5.253, P =0.021; neoadjuvant chemoradiotherapy, OR=3.882, 95%CI: 2.425-6.216, P <0.001), anastomotic leakage (OR=7.960, 95%CI: 4.550-13.926, P <0.001), open laparotomy (OR=3.412, 95%CI: 1.772-6.571, P <0.001), and tumor location (distance of tumor from the anal verge 5-10 cm: OR=2.381, 95%CI:1.227-4.691, P <0.001; distance of tumor from the anal verge <5 cm: OR=5.985,95% CI: 3.039-11.787, P <0.001) were identified as independent risk factors for non-tumor-related anastomotic stenosis. Thereafter, a nomogram prediction model incorporating the four identified risk factors for development of anastomotic stenosis after rectal cancer was developed. The area under the curve of the model ROC was 0.815 (0.773-0.857, P <0.001), and the C-index of the predictive model was 0.815, indicating that the model's calibration curve fitted well with the ideal curve. Conclusion: Non-tumor-related anastomotic stenosis after rectal cancer surgery is significantly associated with neoadjuvant treatment, anastomotic leakage, surgical procedure, and tumor location. A nomogram based on these four factors demonstrated good discrimination and calibration, and would therefore be useful for screening individuals at risk of anastomotic stenosis after rectal cancer surgery.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain., (© 2024. The Author(s).)

Genome-wide sequencing and genetic matchmaker services are propelling a new era of genotype-driven ascertainment of novel genetic conditions. The degree to which reported phenotype data in discovery-focused studies address informational priorities for clinicians and families is unclear. We identified reports published from 2017 to 2021 in 10 genetics journals of novel Mendelian disorders. We adjudicated the quality and detail of the phenotype data via 46 questions pertaining to six priority domains: (I) Development, cognition, and mental health; (II) Feeding and growth; (III) Medication use and treatment history; (IV) Pain, sleep, and quality of life; (V) Adulthood; and (VI) Epilepsy. For a subset of articles, all subsequent published follow-up case descriptions were identified and assessed in a similar manner. A modified Delphi approach was used to develop consensus reporting guidelines, with input from content experts across four countries. In total, 200 of 3243 screened publications met inclusion criteria. Relevant phenotypic details across each of the 6 domains were rated superficial or deficient in >87% of papers. For example, less than 10% of publications provided details regarding neuropsychiatric diagnoses and "behavioural issues", or about the type/nature of feeding problems. Follow-up reports (n = 95) rarely contributed this additional phenotype data. In summary, phenotype information relevant to clinical management, genetic counselling, and the stated priorities of patients and families is lacking for many newly described genetic diseases. The PHELIX (PHEnotype LIsting fiX) reporting guideline checklists were developed to improve phenotype reporting in the genomic era., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is an important factor threatening the health of the elderly. Aging leads to changes in the structure and function of the cardiovascular system, which increases the risk of CVD in the elderly. Cardiac aging is characterized by increased left ventricular wall thickness, increased degree of myocardial fibrosis, increased cardiac hardness, and decreased cardiac function, while vascular aging is characterized by enlarged lumen, thickened wall, and endothelial dysfunction. Promoting healthy cardiovascular aging means reducing the age-related cardiovascular dysfunction and the risks of CVD. Exercise is a crucial means for the treatment and rehabilitation of CVD. Exercise reduces the risk factors of CVD, remodels the cardiovascular structure, and increases the resistance of heart to detrimental stimulus, which promotes healthy cardiovascular aging. The improved mitochondrial function via exercise plays a key role in the health effects of exercise. In addition, exercise promotes the secretion of exerkines in various tissues and organs, which plays a role in reducing inflammation, improving metabolism, inhibiting apoptosis, etc., thus benefiting cardiovascular health. This review discusses the mechanism and potential application of exercise in promoting healthy cardiovascular aging. Exploring the specific mechanisms underlying exercise-induced cardiovascular health and formulating accurate exercise prescriptions for different populations is an important direction to promote healthy cardiovascular aging and prevent CVD.

Energy metabolism is a highly conserved process that balances generation of cellular energy and maintenance of redox homeostasis. It consists of five interconnected pathways: glycolysis, tricarboxylic acid cycle, pentose phosphate, trans-sulfuration, and NAD+ biosynthesis pathways. Environmental stress rewires cellular energy metabolism. Type-2 diabetes is a well-studied energy metabolism rewiring state in human pancreatic β-cells where glucose metabolism is uncoupled from insulin secretion. The two-spotted spider mite, Tetranychus urticae (Koch), exhibits a remarkable ability to adapt to environmental stress. Upon transfer to unfavourable plant hosts, mites experience extreme xenobiotic stress that dramatically affects their survivorship and fecundity. However, within 25 generations, mites adapt to the xenobiotic stress and restore their fitness. Mites' ability to withstand long-term xenobiotic stress raises a question of their energy metabolism states during host adaptation. Here, we compared the transcriptional responses of five energy metabolism pathways between host-adapted and non-adapted mites while using responses in human pancreatic islet donors to model these pathways under stress. We found that non-adapted mites and human pancreatic β-cells responded in a similar manner to host plant transfer and diabetogenic stress respectively, where redox homeostasis maintenance was favoured over energy generation. Remarkably, we found that upon host-adaptation, mite energy metabolic states were restored to normal. These findings suggest that genes involved in energy metabolism can serve as molecular markers for mite host-adaptation., (© 2023. The Author(s).)

Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with lifelong cognitive deficits. However, the mechanisms by which triplication of chromosome 21 genes drive neuroinflammation and cognitive dysfunction are poorly understood. Here, using the Ts65Dn mouse model of DS, we performed an integrated single-nucleus ATAC and RNA-sequencing (snATAC-seq and snRNA-seq) analysis of the adult cortex. We identified cell type-specific transcriptional and chromatin-associated changes in the Ts65Dn cortex, including regulators of neuroinflammation, transcription and translation, myelination, and mitochondrial function. We discovered enrichment of a senescence-associated transcriptional signature in Ts65Dn oligodendrocyte (OL) precursor cells (OPCs) and epigenetic changes consistent with a loss of heterochromatin. We found that senescence is restricted to a subset of OPCs concentrated in deep cortical layers. Treatment of Ts65Dn mice with a senescence-reducing flavonoid rescued cortical OPC proliferation, restored microglial homeostasis, and improved contextual fear memory. Together, these findings suggest that cortical OPC senescence may be an important driver of neuropathology in DS., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Rusu et al.)

The causal association between chronic diseases and depression remains unclear. This study aimed to explore the effects of types and number of chronic diseases on the risk of depression using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). A self-admitted questionnaire was used to obtain data on 14 predefined chronic diseases and the European-Depression Scale (EURO-D) was used to assess depression. Among the 16,080 baseline depression-free participants aged 50+, 31.29% (5032) developed depression over 13 years. Multivariate Cox regression models showed that individuals with any chronic diseases were at higher risk of new onset depression compared to disease-free participants. The risk of new onset depression increased with an increasing number of diseases among both younger (50-64) and older (65+) adults. Individuals with heart attack, stroke, diabetes, chronic lung disease, and arthritis were at increased risk of depression across age groups. However, some age-specific associations were observed, with cancer increasing depression risk among younger- and peptic ulcer, Parkinson's disease and cataracts increasing depression risk among older adults. These findings highlight the importance of managing chronic diseases, especially among those with more than two diseases, to prevent the development of depression among middle-aged and older adults., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Involving in the immune response after cerebral infarction, astrocytes could secrete large amounts of pro- and anti-inflammatory factors. The aim of this study is to investigate the effect of Wnt3a intervention on the inflammatory response of oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) astrocyte model, and to provide a new target for immunoprotective treatment of cerebral infarction. We constructed the OGD/R rat astrocyte model, the astrocytes were treated by different concentrations of glucose (25, 50, 100 mM) intervened with/without Wnt3a (25 µg/ml). Microscope was used to observe the cell survival in rat astrocytes. The relative expression of inflammatory factors (TNF-a, IL-6, HIF-a) in rat astrocytes was detected by qRT-PCR. The expression of inflammatory factors such as TNF-a, IL-6 and HIF-a in rat astrocytes was increased after OGD/R treatment. The Wnt3a intervention promoted cell survival and decreased the expression of inflammatory factors in rat astrocytes induced by OGD/R. There is a neuroprotective effect that Wnt3a intervention could reduce inflammatory response in the OGD/R rat astrocyte model.

Objective: To observe the effects of estradiol on expression of plasma membrane Ca 2+ -ATPase isoform 2 in inner ear of rats. Methods: Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group. Results: There was no significant difference in serum estradiol and progesterone levels among the five groups before operated( P >0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group ( P <0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group ( P >0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group ( P <0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group ( P <0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group ( P <0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group ( P <0.05) while the expression levels underwent no significantly change in E2 and E2+P groups ( P <0.05). Conclusion: The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

Objective: The aim of the study is to investigate the influence of work-related psychological and physical stresses on risk of cardiovascular disease (CVD)., Methods: A total of 5651 CVD-free participants older than 50 years from the Survey of Health, Ageing and Retirement in Europe were followed up for 13 years to detect incident CVD. Work-related stress was assessed using job strain and job reward questionnaire. Cox regression model was used to estimate the association., Results: High physical demands (hazard ratio [HR], 1.30) and low reward (HR, 1.19) compared with their counterparts, as well as active physical jobs (HR, 1.41) and high physical strain (HR, 1.45) in comparison with low physical strain were associated with higher risk of incident CVD after adjusting for confounders. However, combining physically stressful jobs with low reward did not further increase the CVD risk., Conclusions: Avoiding physically stressful jobs or providing appropriate reward may reduce the occurrence of CVD., Competing Interests: Wang, Feng, Zhuo, Yao, Hao, and Pei have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Purpose: To explore the relationship between blood-brain barrier (BBB) leakage and brain structure in non-brain metastasis lung cancer (LC) by magnetic resonance imaging (MRI) as well as to indicate the possibility of brain metastasis (BM) occurrence., Patients and Methods: MRI were performed in 75 LC patients and 29 counterpart healthy peoples (HCs). We used the Patlak pharmacokinetic model to calculate the average leakage in each brain region according to the automated anatomical labeling (AAL) atlas. The thickness of the cortex and the volumes of subcortical structures were calculated using the FreeSurfer base on Destrieux atlas. We compared the thickness of the cerebral cortex, the volumes of subcortical structures, and the leakage rates of BBB, and evaluated the relationships between these parameters., Results: Compared with HCs, the leakage rates of seven brain regions were higher in patients with advanced LC (aLC). In contrast to patients with early LC (eLC), the cortical thickness of two regions was decreased in aLCs. The volumes of twelve regions were also reduced in aLCs. Brain regions with increased BBB penetration showed negative correlations with thinner cortices and reduced subcortical structure volumes (P<0.05, R=-0.2 to -0.50). BBB penetration was positively correlated with tumor size and with levels of the tumor marker CYFRA21-1 (P<0.05, R=0.2-0.70)., Conclusion: We found an increase in BBB permeability in non-BM aLCs that corresponded to a thinner cortical thickness and smaller subcortical structure volumes. With progression in LC staging, BBB shows higher permeability and may be more likely to develop into BM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Ma, Yang, Zhang, He, Feng, Shan, Xu, Ding and Cheng.)

Hepatocellular carcinoma (HCC) has high mortality. The option of systemic therapy has increased significantly over the past five years. Sorafenib was the first multikinase inhibitor, introduced in 2007, as a treatment option for HCC, and it was the only effective systemic treatment for more than ten years. It was not until 2017 that several breakthroughs were made in the development of systemic strategies. Lenvatinib, another multikinase inhibitor, stood out successfully after sorafenib, and has been applied to clinical use in the first-line setting. Other multikinase inhibitors such as regorafenib, ramucirumab and cabozantinib, were approved in quick succession as second-line therapies. Concurrently, immune checkpoint inhibitors (ICIs) have readily become established treatments for many solid tumors, including HCC. The most studied ICIs to date, target programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These ICIs have demonstrated efficacy in treating advanced HCC. More recently, combination of bevacizumab and atezolizumab (ICI targeting PD-L1) was approved as the gold-standard first-line therapy. Combination of ICIs with nivolumab and ipilimumab was also approved in the second-line setting for those who failed sorafenib. At the moment, numerous clinical trials in advanced HCC are underway, which will bring continuous change to the management, and increase the survival, for patients with advanced HCC. Our review article: (1) summarizes United States Food and Drug Administration (US FDA) approved systemic therapies in advanced HCC, (2) reports the evidence of currently approved treatments, (3) discusses potential drugs/drug combinations being currently tested in phase III clinical trials, and (4) proposes possible future directions in drug development for advanced HCC.

Objectives: The purpose of this study was to investigate the value of high-frequency ultrasound and shear wave elastography (SWE) in quantitative differential diagnosis of high-risk and low-risk basal cell carcinomas (BCCs)., Methods: A total of 52 BCCs confirmed by surgical pathology were studied. Taking pathologic subtypes as reference, all the cases were classified as high-risk BCCs or low-risk BCCs. High-frequency ultrasound parameters and SWE parameters recorded preoperatively were retrospectively analyzed. The differences of two groups were compared., Results: There were 12 high-risk BCCs and 40 low-risk BCCs. The maximum infiltration depth (MID) and average Young's modulus (E ave ) of high-risk BCCs were 5.76 ± 2.56 mm and 31.61 ± 12.36 kPa, whereas of low-risk BCCs were 4.29 ± 1.77 mm and 20.04 ± 4.74 kPa, respectively, P < .05. The area under the receiver operator characteristic curve of MID and E ave were 0.714 and 0.811, P > .05. Taking 5.5 mm of MID and 24.45 kPa of E ave as the threshold for the diagnosis of high-risk BCCs, the sensitivity, specificity, and accuracy were 58.3%, 82.5%, 76.9% and 75.0%, 82.5%, 80.8%, P > .05., Conclusions: The MID and E ave of the lesion can be used to determine the recurrence risk of BCCs and provide a reference for the development of individualized treatment plans., (© 2021 American Institute of Ultrasound in Medicine.)

Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.

Reaction of [(3-bdppmapy)(AuCl) 2 ] with NaHmba (3-bdppmapy = N , N '-bis-(diphenylphosphanylmethyl-3-aminopytidine, H 2 mba = 2-mercaptobenzoic acid) resulted in a new tetranuclear Au/P/S complex [(3-bdppmapy) 2 (AuHmba) 3 (AuCl)] (1). Upon excitation at 370 nm, 1 exhibited solid state, room temperature, green fluorescent emission (QY = 4.7%, τ = 2.58 ns) which was significantly enanced at lower temperatures due to strengthening of the Au-Au interaction. Different ratios of 1 with phosphor N630 in PMMA were used to make thermochromic photoluminescent films and fibres that could be fabricated into an optical thermometer sensitive over temperature ranges 80-300 K and 300-370 K.

Exophiala is an important genus, with several species associated with infections in humans and animals. In a survey of soil fungal diversity in Yunnan province, PR China, a novel taxon, Exophiala pseudooligosperma sp. nov., was identified based on combined morphological and molecular phylogenetic features. Morphologically, this species is characterized by having torulose, septate hyphae and swollen, terminal or intercalary conidiogenous cells arising at acute angles from aerial hyphae. Phylogenetic analysis of the combined sequences of the internal transcribed spacer, the small and large nuclear subunit of the rRNA gene and part of the β-tubulin gene confirmed the phylogenetic position of the new species within the genus Exophiala .

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role. But the positive effects of non-volatile acylphloroglucinols, a class of specialized metabolites with relatively high content in Eucalyptus, should not be neglected. Herein, non-volatile acylphloroglucinols from leaves of Eucalyptus robusta were evaluated for their abilities to inhibit Zika virus (ZIKV) which is associated with severe neurological damage and complications. The results showed eucalyprobusone G, a new symmetrical acylphloroglucinol dimer, possessed the significant ability to inhibit ZIKV without inducing cytotoxicity. The EC 50 values of eucalyprobusone G against the African lineage (MR766) and Asian lineage (SZ-WIV01) of ZIKV were 0.43 ± 0.08 and 10.10 ± 3.84 μM which were 110 times and 5.8 times better than those of the reference compound ribavirin, respectively. Further action mode research showed that eucalyprobusone G impairs the viral binding and RdRp activity of NS5. The results broaden the functional properties of Eucalyptus robusta and indicate acylphloroglucinol dimers could be developed as anti-ZIKV agents., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings., Methods: Clinicopathological and CT data from 57 patients, who were diagnosed with duodenal lipoma at the first affiliated Hospital of Zhengzhou University (Zhengzhou, China) between June 2014 and March 2019, were retrospectively reviewed. Data collected included location and size of the tumor, morphological manifestations (shape, density, boundary), concomitant diseases, pathology and gastroscopy results, and follow-up. Follow-up was performed via telephone, and surgical patients were followed-up for recurrence, metastasis and tumor size, and morphological changes. The follow-up period was up to January 2019., Results: Of the 57 patients with duodenal lipoma, contrast-enhanced scanning was performed in 7 cases. The tumor was located in the descending duodenum in 33 cases, the ascending in 4 cases, the horizontal in 16 cases, and the bulb in 4 cases. Mean tumor size was 13.0 ± 5.8 mm. CT morphological features of the tumor were as follows: tumor shape, round, quasi-round, or oval (n = 42); long strip (n = 3); nodular (n = 2); triangular (n = 1); and irregular lobulated (n = 9). Among the 57 patients, tumor density was homogeneous in 52 cases, inhomogeneous in 4 cases, and nodular with calcification in 1 case. The tumor boundary was classified as clear and with no capsule. Diseases concomitant with the tumor were as follows: gastritis (n = 23), gastric adenocarcinoma (n = 1), and gastric lymphoma (n = 1). Esophageal disease was found in 16 cases, including reflux esophagitis (n = 12) and esophageal cancer (n = 4). There were 13 cases of gallbladder and biliary disease, including cholecystolithiasis and cholecystitis (n = 9), common bile duct disease (n = 2), colorectal cancer (n = 4), lung cancer (n = 2), duodenal carcinoma with obstruction (n = 1), and ureteral space narrowing (n = 1)., Conclusion: CT was an effective, non-invasive method for diagnosis of duodenal lipoma. CT imaging could clearly discern location, size, shape, and nature of duodenal lipomas. Duodenal lipoma can be associated with digestive tract inflammatory diseases and tumors in different locations, and its diagnosis is potentially valuable for their prevention and treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith., Methods: The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression., Results: The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90., Conclusion: Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo., (© 2021. Huazhong University of Science and Technology.)

Background/aims: This study evaluates the association between the eradication of Helicobacter pylori (H. pylori) and gastroesophageal reflux disease (GERD)., Materials and Methods: Relevant studies were identified by conducting literature search in PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases. The prevalence rates of gastroesophageal reflux, heartburn, epigastric pain, and nausea were extracted from the identified research articles and were used in meta-analysis of relative risks (RR) to achieve an overall effect size of the relationship between H. pylori eradication and GERD., Results: A total of 19 randomized controlled trials were included in this meta-analysis. The prevalence of gastroesophageal reflux was significantly higher in patients with H. pylori eradication compared with patients without it (RR: 1.54, 95% CI: 1.06-2.24; p=0.02). A subgroup analysis did not identify any significant difference in GERD prevalence in studies conducted outside China (RR: 1.62, 95% CI: 0.98-2.68) or in China (RR: 1.30, 95% CI: 0.76-2.22). There were no significant differences in heartburn (RR: 1.03, 95% CI: 0.88-1.20), epigastric pain (RR: 0.98, 95% CI: 0.13-7.56), or nausea (RR: 0.44, 95% CI: 0.07-2.72) risk between patients with and without H. pylori eradication., Conclusion: Eradication of H. pylori infection is found to be associated with GERD, although regional differences may exist in the prevalence. Well-designed studies especially those with stratification of patients' basic conditions are needed to seek refined evidence of the association between H. pylori eradication and the GERD.

Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC 50 values of 3.22 ± 0.36, 3.82 ± 0.22, and 2.55 ± 0.28 μΜ, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate the changes of serum estradiol（E2） and otolith structural protein Otolin-1 levels in postmenopausal women with benign paroxysmal positional vertigo（BPPV）. Method: Forty postmenopausal women diagnosed as primary BPPV were selected as the experimental group. Meanwhile, 40 postmenopausal women without vertigo during the same time were selected as the control group. 4 ml of fasting peripheral venous blood was extracted in the morning, and E2 and Otolin-1 protein levels in serum of the two groups were detected by electrochemiluminescence（ECL） and ELISA, respectively. Result: ①The serum level of E2 in the experimental group was（29.11±15.11） pg/ml, which was lower than that in the control group（37.18±12.24） pg/ml（ P =0.010）. ②The serum level of Otolin-1 in the experimental group was（361.55±186.14） pg/ml, which was significantly higher than that in the control group（282.61±139.98） pg/ml（ P =0.035）. ③Spearman correlation analysis was carried out on the serum levels of Otolin-1 and E2 in the experimental group and the control group, respectively, and no correlation was found between them（ P =0.403 and 0.363, respectively）. ④In the control group, age was negatively correlated with serum E2 level（ P =0.044, r =-0.320）, suggesting that age was only weakly correlated with E2 level. However, in the experimental group, there was no correlation between the two（ P =0.148）. ⑤There was no correlation between age and serum Otolin-1 level in the two groups（ P =0.705 and 0.076, respectively）. Conclusion: Compared with postmenopausal patients without vertigo, the level of E2 in postmenopausal BPPV patients decreased, but the level of Otolin-1 increased significantly. Therefore, the serum level of Otolin-1 may be used as a bio-marker to assist the diagnosis and efficacy evaluation of postmenopausal women with BPPV., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) ( t= 5.146, P< 0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)( t= 21.800, P< 0.05; t= -18.490, P< 0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm(3)) was significantly larger than that in the control group((566.414±81.087) mm(3)) by treated with nab-paclitaxel( t= 4.230, P< 0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions: The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.

Objective: To investigate the risk factors of anastomotic leakage (AL) after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy and construct a nomogram prediction model. Methods: This study was a retrospective case-control study that collected and reviewed the clinicopathological data of 359 patients who underwent laparoscopic surgery from January 2012 to January 2018, including 202 patients from the Department of General Surgery, Nanfang Hospital of Southern Medical University and 157 patients from the Department of Gastrointestinal Surgery of Fujian Provincial Cancer Hospital. Inclusion criteria: (1) age ≥ 18 years old; (2) diagnosis as rectal cancer by biopsy before treatment; (3) distance from tumor to anus within 12 cm; (4) locally advanced stage (T3-T4 or N+) diagnosed by imaging (CT, MRI, PET or ultrasound); (5) standardized neoadjuvant therapy followed by laparoscopic radical operation. Exclusion criteria: (1) previous history of colorectal cancer surgery; (2) short-term or incomplete standardized neoadjuvant therapy; (3) Miles, Hartmann, emergency surgery, palliative resection; (4) conversion to open surgery. Clinicopathological data, including age, gender, body mass index (BMI), preoperative albumin, distance from tumor to anus, operation hospital, American Society of Anesthesiologists score (ASA score), operation time, T stage, N stage, M stage, TNM stage, pathological complete response (pCR) were analyzed with univariate analysis to identify predictors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. Then, incorporated predictors of AL, which were screened by multivariate logistic regression, were plotted by the "rms" package in R software to establish a nomogram model. According to the scale of the nomogram of each risk factor, the total score could be obtained by adding each single score, then the corresponding probability of postoperative AL could be acquired. The area under ROC curve (AUC) was used to evaluate the predictive ability of each risk factor and nomogram on model. AUC > 0.75 indicated that the model had good predictive ability. The Bootstrap method (1000 bootstrapping resamples) was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index) whose rage was 0.5 to 1.0. Higher C-index indicated better consistency with actual risk. The calibration curve was used to assess the calibration of prediction model. The Hosmer-Lemeshow test yielding a non-significant statistic ( P >0.05) suggested no departure from the perfect fit. Results: Of 359 cases, 224 were male, 135 were female, 189 were ≥ 55 years old, 98 had a BMI > 24 kg/m(2), 176 had preoperative albumin ≤ 40 g/L, 128 had distance from tumor to anus ≤ 5 cm, 257 were TNM 0-II stage, 102 were TNM III-IV stage, and 84 achieved pCR after neoadjuvant therapy. The incidence of postoperative AL was 9.5% (34/359). Univariate analysis showed that gender, preoperative albumin and distance from tumor to the anus were associated with postoperative AL (All P <0.05). Multivariate logistic regression analysis revealed that male (OR=2.480, 95% CI: 1.012-6.077, P =0.047), preoperative albumin ≤40 g/L (OR=5.319, 95% CI: 2.106-13.433, P <0.001) and distance from tumor to anus ≤ 5 cm (OR=4.339, 95% CI: 1.990-9.458, P <0.001) were significant independent risk factors for postoperative AL. According to these results, a nomogram prediction model was constructed. The male was for 55 points, the preoperative albumin ≤ 40 g/L was for 100 points, and the distance from tumor to the anus ≤ 5 cm was for 88 points. Adding all the points of each risk factor, the corresponding probability of total score would indicated the morbidity of postoperative AL predicted by this nomogram modal. The AUC of the nomogram was 0.792 (95% CI: 0.729-0.856), and the C-index was 0.792 after internal verification. The calibration curve showed that the predictive results were well correlated with the actual results ( P =0.562). Conclusions: Male, preoperative albumin ≤ 40 g/L and distance from tumor to the anus ≤ 5 cm are independent risk factors for AL after laparoscopic surgery in rectal cancer patient with neoadjuvant therapy. The nomogram prediction model is helpful to predict the probability of AL after surgery.

In this paper, we employed a direct analysis in real time (DART) ion source coupled to QTRAP mass spectrometry for the analysis of chloramphenicol (CAP) in honey. The accuracy of the DART-MS/MS method for the analysis of CAP in honey was evaluated by comparison with data generated by a validated HPLC-MS/MS method. The sample preparation procedure was optimized to obtain sensitive and accurate determination of trace CAP residue in honey at concentrations less than 1.0 µg/kg. The DART-MS/MS method offers faster analysis time, lower cost per analysis, and reduced matrix effects and simplicity compared to HPLC-MS/MS method. Fifty-two honey samples collected from a Chinese market were analyzed using two methods. The results of the two methods are in good agreement, suggesting DART-MS/MS as a potential technique for the direct detection of trace amounts of veterinary drugs in complex matrixes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Epstein-Barr virus-encoded LMP1 plays a critical role in the carcinogenesis of nasopharyngeal carcinoma (NPC), but the mechanism remains elusive. We aimed to analyze the expression and clinical pathological significance of provirus integration site for Moloney murine leukemia virus 1 (Pim1) in clinical NPC, and to elucidate the effect of LMP1 on Pim1 expression and its mechanism., Methods: Immunohistochemical staining was used to detect the expression of Pim1 in clinical NPC tissues and control nasopharyngeal chronic inflammation (NPI) tissues, and the correlation between Pim1 and clinical parameters of NPC patients was analyzed. The LMP1 stable expression cell line CNE1-LMP1-OV was constructed through infecting the well-differentiated nasopharyngeal carcinoma cells CNE1 with LMP1 overexpressing lentivirus. Then the in vivo experiments were conducted., Results: Among 89 NPC patients, 48 cases (53.93%) were positive for Pim1, while only one case was Pim1 positive in 15 NPI controls (6.67%). Pim1 expression was not correlated with gender, age, smoking status and clinical classification of NPC patients, but positively correlated with T, N and M classification. CNE1-LMP1-OV cell line was successfully established, which displayed a higher cell proliferation ability and Pim1 expression. NF-κB inhibitor PDTC, PKC inhibitor GF109203X and STAT3 inhibitor Stattic significantly attenuated LMP1-induced Pim1 expression, and while AP-1 inhibitor SR11302 showed no inhibitory effect. Interestingly, Pim1 inhibitor quercetagetin significantly inhibited the proliferation of CNE1-LMP1-OV cells., Conclusion: LMP1 mediates Pim1 expression through NF-κB, PKC and STAT3 signaling, which promotes the proliferation of NPC cells and participate in the clinical progression of NPC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The insulinoma, which is the most common pancreatic neuroendocrine tumor, can be misdiagnosed and mistreated easily.Recently, the misdiagnosis rate has decreased significantly owing to the establishment of diagnosis and treatment system.However, the misconception about its diagnosis and treatment still exists because the diagnosis and treatment level varies greatly among different centers.This article aims to summarize the experience in the diagnosis and treatment of insulinoma in Peking Union Medical College Hospital, and introduce the qualitative and localization diagnosis, surgical and interventional treatment and perioperative management about insulinoma, so as to standardize the diagnosis and treatment procedure in China.

The aim of this work was to study the expression of SOX2 gene in triple negative breast cancer and its role. One hundred and twenty specimens of paraffin-embedded triple negative breast cancer (TNBC) tissues were collected from Harbin Medical University Cancer Hospital, Heilongjiang, China between January 2014 and March 2018. The expression of SOX2 was detected using immunohistochemistry, and the relationship between the expression of SOX2 and clinical features was analyzed. Breast cancer cell lines (normal group, SOX2 interference group, SOX2 overexpression group) were cultured in vitro to detect the proliferation and cloning ability of the cell lines. The expression of SOX2 was related to lymph node metastasis and stage of breast cancer (P less than 0.05), but was not related to age, menopause or tumor size (P > 0.05); the expression of SOX2 in the overexpression group was significantly greater than that in the normal group after 72 hours, and no significant difference between the overexpression group and the interference group was observed. The number of clone cells with a diameter of 0.5 mm in the interference group was lower compared to the normal group, and that of the overexpression group was higher, but not significant. SOX2 is associated with the high invasiveness of breast cancer and can be used as a therapeutic target to inhibit the metastasis of cancer cells. SOX2 can promote the proliferation of breast cancer cells and affect the size of clone cells in its involvement in clone.

Eucalyptusdimers A-C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (±)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects.

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ(2) test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues ( P <0.05). KLK7 expression was correlated with vascular invasion(χ(2)=7.535, P <0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ(2)=7.535, P <0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group ( t =4.479, P <0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group( t =2.831, P <0.05). Conclusions: The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.

Dental caries are the most prevalent chronic infections in the oral cavity, and Streptococcus mutans acts as the main cariogenic bacterial species. Antibacterial quaternary ammonium compounds (QAs) have been developed to preveFnt or treat dental caries. However, there is no report on the tolerance of S. mutans to QAs. In this study, we investigated the development of S. mutans persistence induced by a novel dental caries defensive agent, dimethylaminododecyl methacrylate (DMADDM), for the first time. Typical biphasic killing kinetics for persisters were observed in both S. mutans planktonic and biofilm cultures challenged by DMADDM at concentrations of 20 and 200 μg·mL -1 , respectively. The persisters tolerated six other antibiotics with different antibacterial mechanisms, while only daptomycin and vancomycin could slightly reduce the persister numbers in planktonic cultures. The distribution of persisters in DMADDM-treated biofilms was similar to that in the untreated control, except that the total biomass and biofilm height were significantly reduced. A higher exopolysaccharides (EPS):bacteria ratio was observed in DMADDM-treated biofilms. Persisters in biofilms significantly upregulated gtf gene expression, indicating an increase in the bacteria's ability to produce EPS and an elevated capability of cariogenic virulence. Carbon source metabolism was significantly reduced, as related metabolic genes were all downregulated in persisters. Concentrations of 0.1 mM, 1 mM and 10 mM of extra glucose significantly reduced the number of persisters both in planktonic and biofilm conditions. The formation of non-inheritable and multidrug tolerant persisters induced by DMADDM suggested that drug tolerance and new persistent eradication strategies should be considered for oral antibacterial agents.

Psidium guajava L., a species native to South America, has been widely cultivated in the tropical and subtropical areas of China for its popular fruits. The preliminary analysis by liquid chromatography-ultraviolet (LC-UV) indicated the presence of meroterpenoids in the fruits of P. guajava (guava). Subsequent fractionation of the petroleum ether extract resulted in the identification of two new meroterpenoids, psiguajavadials A (1) and B (2), together with 14 previously described meroterpenoids (3-16). Their structures were fully elucidated by comprehensive spectroscopic techniques and theoretical calculations. All of the meroterpenoids showed cytotoxicities against five human cancer cell lines, with guajadial B (12) being the most effective having an IC 50 value of 150 nM toward A549 cells. Furthermore, biochemical topoisomerase I (Top1) assay revealed that psiguajavadial A (1), psiguajavadial B (2), guajadial B (12), guajadial C (14), and guajadial F (16) acted as Top1 catalytic inhibitors and delayed Top1 poison-mediated DNA damage. The flow cytometric analysis indicated that the new meroterpenoids psiguajavadials A (1) and B (2) could induce apoptosis of HCT116 cells. These data suggest that meroterpenoids from guava fruit could be used for the development of antitumor agents.

Objective: To test the expression of miR-1178 in pancreatic cancer and study its clinicopathological significance and mechanism. Methods: The expression of miR-1178 in 87 paired paraffin pancreatic ductal adenocarcinoma specimens and adjacent non- cancerous pancreatic tissue diagnosed by Pathology Department of Peking Union Medical College Hospital was detected by hybridization in situ. The relationship between the expression of miR-1178 and clinicopathological characters was analyzed.miR-1178 mimics and inhibitor were used to further detect the close relationship among miR-1178 and cancer invasion. Establish a nude mice subcutaneously transplanted tumor model, 4 weeks after vaccination for tumor volume and weight measurement.Student t -test, rank sum test, and χ(2) test was used respectively to compare the data between two groups. Cox regression was adopted to improve the single factor and multiple factors analysis. Results: The results of hybridization in situ showed the expression of miR-1178 was increased in 72 cases with pancreatic cancer compared to that in paired normal pancreatic tissues (50/72 vs . 11/72, χ(2)=43.26, P <0.05). miR-1178 expression was positively associated with tumor lymph node stage (χ(2)=4.189, P =0.041). Univariate and multivariate analysis revealed that miR-1178 was an independent adverse prognostic indicator for patients with pancreatic cancer ( HR =2.364, 95% CI : 1.114-5.019, P =0.025). Transwell assay indicated the over-expression of miR-1178 increased the number of AsPC-1 cells that penetrated the ECM-coated membrane (177.0±19.8 vs . 119.7±15.9)(χ(2)=8.21, P <0.05). For the in vivo experiment, overexpression of miR-1178 significantly promoted tumor growth, compared with control group (tumor volume: (5 122.4±760.2)mm(3) vs . (1 976.8±601.8)mm(3), t =2.413, P <0.05; tumor weight: (1.55±0.21)g vs . (0.67±0.17)g, t =2.960, P <0.05). Over-expression of miR-1178 down-regulated the expression of Stub1 and elevated the expression of FAK/MMP-9 signal pathway( P <0.05). Conclusions: MiR-1178 is overexpressed in pancreatic cancer, and is effective for predicting patients' prognosis. MiR-1178 regulate Stub1/FAK/MMP-9 signal pathway and promote the invasion of AsPC-1 cells.

Laparoscopic pancreaticoduodenectomy (LPD) is one of the most complicated operations in laparoscopic field.After been widely reported nowadays, LPD has been cautiously regarded as feasible and safe for radically resection.At present, several large pancreatic surgery centers in China have successively carried out this kind of surgery, with over one thousand cases in all.However, partly due to its complexity and steep learning curve, this procedure only remains limited to a few selected large pancreatic centers.Large sample prospective random control test studies are still required.We suggest that in China, LPD should only be developed steadily and step by step by highly skilled open and laparoscopic surgeons who have minimally invasive concept, contrary to fears and could grasp technical expertise.

Purpose: To compare the postoperative intraocular pressure (IOP) and incidence of early complications after trabeculectomy with releasable suture to standard trabeculectomy in Chinese patients with primary angle-closure glaucoma., Patients and Methods: One hundred seventy-five patients diagnosed as primary angle-closure glaucoma with 6 clock-hours or more of peripheral anterior synechia were randomly allocated to 2 treatment groups: 87 underwent standard trabeculectomy (S group: 2 interrupted permanent sutures to the scleral flap) and 88 received trabeculectomy with 2 permanent and 2 releasable sutures (R group). The postoperative IOP and complications during the first 3 months after surgery were compared., Results: One hundred seventy-one patients (97.7%) attended the 3-month visit. The IOP in the first week after trabeculectomy was significantly higher in the R group: day 1, 17.3±8.6 versus 12.7±6.0 mm Hg (P<0.001); day 3, 18.0±7.3 versus 12.9±6.3 mm Hg (P<0.001); day 7, 14.8±6.3 versus 12.0±4.9 mm Hg (P=0.001), but no difference was observed after the second week (P=0.659 to 0.753). The incidence of transient hypotony was higher in S group (20.4%) than the R group (9.1%) (P=0.046); hypotony recovered in 80.8% (21/26) within 1 week. There was no difference in the occurrence of shallow chamber, choroidal detachment, macular edema, additional surgery, or hyphema (P=0.56 to 1.0)., Conclusions: The technique of releasable sutures for trabeculectomy used in this study did not demonstrate significant advantages over standard trabeculectomy. Releasable sutures were associated with some decrease in visual acuity and increase in postoperative complaints.

In the present study, we isolated and screened an antitumor polysaccharide (PGP2a) from the roots of Panax ginseng. Chemical composition analysis indicated PGP2a was an acidic protein-polysaccharide. The average molecular weight was estimated to be 3.2 × 10(4)Da. According to gas chromatography (GC) result, PGP2a consisted of galactose, arabinose, glucose and galacturonic acid in the molar ratio of 3.7:1.6:0.5:5.4, respectively. MTT assay showed that PGP2a had a potent inhibitory effect on the growth of HGC-27 cells in a dose-dependent fashion. Furthermore, the number of HGC-27 cells arrested in G2/M phase, and the percentage of apoptotic cells were increased in response to PGP2a treatment along with concentration increasing. Moreover, western blotting analysis showed that protein expressions of Twist and AKR1C2 were suppressed by PGP2a, whereas an increase of NF1 was observed at protein level. Taken together, these findings suggested that PGP2a could be developed as a novel antitumor agent acting on Twist related gene for human gastric cancer therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Mutations, such as single nucleotide polymorphisms (SNPs), in the 5′-flanking and microRNA (miRNA) regulatory regions may result in altered gene expression levels and cause diseases. Alpha-2-macroglobulin (A2M) has the function of binding host or foreign peptides and particles, and thereby serves as a defense barrier against pathogens in the plasma and tissues of animals. To investigate the functional markers of the A2M gene associated with mastitis, the promoter was characterized and SNPs that affect promoter activity or binding affinity with the target miRNA were identified using the luciferase reporter assay and real-time quantitative PCR method. Results showed that the core promoter of A2M was found between the bases g.-2641 and g.-2479. Four novel SNPs (g.-724A>G, g.-665G>A, g.-535C>G and g.-520&#95;-519insA) in the promoter region were completely linked. The activity of the mutant haplotype (GAGA) increased by 177% compared with that of the wild haplotype (AGC-). Bta-miR-2898 was upregulated by 6.25-fold in the mammary gland tissues of mastitis-infected cows compared with that of the healthy cows. One SNP (c.4659&#95;4661delC) located in the 3′-untranslated region of the A2M gene may affect the binding affinity with the target bta-miR-2898. Five SNPs exhibited tight linkage. Association analysis showed that the milk somatic cell score for cows with the mutant haplotype (GAGA-) was lower than that for cows with the wild haplotype. Thus, the mutant type can be used as a potential functional marker for a mastitis resistance breeding program in dairy cows. Our findings provided the molecular basis for A2M transcriptional and post-transcriptional regulations. A close relationship between regulatory mutations and mastitis susceptibility of cows also was established.

The sperm flagella 2 (SPEF2) gene is essential for development of normal sperm tail and male fertility. In this study, we characterized first the splice variants, promoter and its methylation, and functional single-nucleotide polymorphisms (SNPs) of the SPEF2 gene in newborn and adult Holstein bulls. Four splice variants were identified in the testes, epididymis, sperm, heart, spleen, lungs, kidneys, and liver tissues through RT-PCR, clone sequencing, and western blot analysis. Immunohistochemistry revealed that the SPEF2 was specifically expressed in the primary spermatocytes, elongated spermatids, and round spermatids in the testes and epididymis. SPEF2-SV1 was differentially expressed in the sperms of high-performance and low-performance adult bulls; SPEF2-SV2 presents the highest expression in testis and epididymis; SPEF2-SV3 was only detected in testis and epididymis. An SNP (c.2851G>T) in exon 20 of SPEF2, located within a putative exonic splice enhancer, potentially produced SPEF2-SV3 and was involved in semen deformity rate and post-thaw cryopreserved sperm motility. The luciferase reporter and bisulfite sequencing analysis suggested that the methylation pattern of the core promoter did not significantly differ between the full-sib bulls that presented hypomethylation in the ejaculated semen and testis. This finding indicates that sperm quality is unrelated to SPEF2 methylation pattern. Our data suggest that alternative splicing, rather than methylation, is involved in the regulation of SPEF2 expression in the testes and sperm and is one of the determinants of sperm motility during bull spermatogenesis. The exonic SNP (c.2851G>T) produces aberrant splice variants, which can be used as a candidate marker for semen traits selection breeding of Holstein bulls.

Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca(2+) channel Orai1 and inducing Ca(2+) influx at the cell surface. Importantly, SPCA2-mediated Ca(2+) signaling is uncoupled from its conventional role of Ca(2+)-ATPase and independent of store-operated Ca(2+) signaling pathway. SPCA2-induced store-independent Ca(2+) entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics.

Purpose: To evaluate the daytime fluctuation of intraocular pressure (IOP) in patients with primary angle-closure glaucoma (PACG) after trabeculectomy., Participants and Methods: A total of 176 patients with PACG participated in a clinical trial of trabeculectomy with or without releasable sutures. Applanation IOP was measured at 5, 7, and 10 AM, and 2, 6, and 10 PM at 3 months posttrabeculectomy. We documented the mean, peak, and trough IOPs, determined the fluctuation of daytime IOP, and explored the associations of IOP fluctuation with baseline factors., Results: IOP measurements were obtained in 173 patients. The mean daytime IOP was 13.2±3.7 mm Hg; mean peak IOP 15.1±4.1 mm Hg, mean trough IOP 11.3±3.5 mm Hg, and mean fluctuation 3.8±2.1 mm Hg. Fluctuation was positively correlated with peak (r=0.528, R2=0.28, P<0.001) and mean IOP (r=0.278, R2=0.08, P<0.001), but not with the trough IOP (r=0.015, P=0.843). Fluctuation was lower with extent of bleb (0.6 mm Hg/unit increase in extent; 95% CI, 0.1-1.2 mm Hg) and in blebs with microcysts (1.1 mm Hg less fluctuation; 95% CI, 0.2-1.9 mm Hg). Fluctuation was not associated with sex, age, baseline IOP, extent of peripheral anterior synechia or number of glaucoma medications before surgery, mean deviation of the visual field, vertical cup:disc ratio, or the use of releasable sutures., Conclusions: The mean fluctuation of daytime IOP after trabeculectomy for PACG was about 4 mm Hg. The fluctuation was positively associated with higher peak and mean IOP and negatively associated with extent of bleb and presence of microcysts.

It was previously reported that an antitumor polysaccharide (PGPW1) was isolated from the root of Panax ginseng. To extend our study, we investigated here the anti-invasive and metastatic effects of PGPW1 on human gastric cancer cell line HGC-27 and tried to determine its possible mechanism of action. Both scratch wound-healing and Transwell assay identified that PGPW1 dose-dependently inhibited migration and invasiveness of HGC-27 cells. Furthermore, results of western blot showed that protein levels of Twist and AKR1C2 were inhibited by PGPW1, whereas an increase of NF1 was observed. Moreover, down-regulation of Twist expression by PGPW1 blocked epithelial-mesenchymal transition (EMT), characterized by a gain of epithelial cell markers, E-cadherin, and loss of the mesenchymal markers, vimentin and N-cadherin, at protein levels. Collectively, we confirmed that PGPW1 decreased migration and invasion of HGC-27 cells by regulation of Twist, AKR1C2, NF1, E-cadherin, vimentin and N-cadherin expression. In conclusion, PGPW1 may serve as a powerful chemopreventive agent against gastric cancer metastasis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the association between early and late postoperative intraocular pressure (IOP) and determine if early postoperative IOP can predict the surgical outcome., Methods: A total of 165 consecutive patients with primary angle-closure glaucoma (PACG) undergoing primary mitomycin-C-augmented trabeculectomy underwent a comprehensive eye examination before surgery and were followed-up on days 1, 7, 14, and 30, and months 3, 6, 12, and 18. IOPs on days 1, 7, 14, and 30 were stratified into groups A (<10 mm Hg), B (≥10 and <15 mm Hg), C (≥15 and <20 mm Hg), and D (≥20 mm Hg). Differences between groups were analyzed using analysis of variance (ANOVA) and Fisher's exact test. Multivariable regression was used to exam the predictive ability of early IOP for final outcome., Results: The mean age was 62.5±7.9 years and 41.21% (n=68) were males. Stratified by IOP on days 1, 7, 14, and 30, respectively, mean IOPs at month 18 were different among groups A, B, C, and D (ANOVA, P=0.047, P=0.033, P=0.008, and P<0.001, respectively). Once the IOPs were settled with interventions on day 7 a higher IOP level was associated with decreasing success rate under different outcome definitions, final IOP <15 mm Hg (Fisher's exact P=0.001) and <20 mm Hg (P=0.039) without medication. Multiple regression showed early IOP predicted final IOP independently from baseline variables. A cutoff value of 13.5 mm Hg on day 7 achieved an accuracy of 80.0 and 57.1% in predicting IOP<15 mm Hg without medication and failure after surgery, respectively., Conclusions: The IOP at 18 months following primary antifibrotic-augmented trabeculectomy in PACG patients is associated with and predicted by the postoperative IOPs at 1 month. Control of early IOP to 13.5 or less may provide better outcomes.

Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various cancers. Previously, we found that myeloid cell leukemia sequence 1 (Mcl1) was downregulated in DADS-induced cell cycle arrest in HL-60 human leukemia cells. Here, we investigated the role of this protein in DADS-induced G2/M cell cycle arrest in HL-60 cells. We demonstrated that DADS treatment significantly increased the proportion of G2/M phase HL-60 cells (P<0.05) and caused a time-dependent significant downregulation of Mcl1 and the cell cycle-related proteins PCNA and CDK1 (P<0.05). Small interfering RNA-mediated knockdown of Mcl1 expression in HL-60 cells arrested the cell cycle in G2/M phase. By co-immunoprecipitation, we demonstrated that Mcl1 associated with PCNA and CDK1 in G2/M cell cycle arrest in DADS-treated HL-60 cells. DADS decreased the interaction of Mcl1 with PCNA and CDK1, leading to G2/M cell cycle arrest in HL-60 cells. Mcl1 plays an important role in DADS-induced G2/M cell cycle arrest in HL-60 human leukemia cells.

Objective: To evaluate the correlation between morphologic appearance of blebs at 3 month and long-term intraocular pressure (IOP) effect in patients with primary angle-closure glaucoma (PACG) after trabeculectomy., Methods: Multi-centered cases series. Data were collected from 176 patients aged ≥ 40 years with PACG who were participated in a randomized clinical trial that aimed at addressing the efficacy of augmented releasable sutures after trabeculectomy. The bleb morphology was graded using the Modified Indian Bleb Appearance Grading Scale (IBAGS) based on standard photos at 3 month after trabeculectomy. IOPs were measured with Goldmann applanation tonometer. The correlation between bleb components and other selected testing influencing factors and long-term IOP was tested by linear Logistic regression analysis., Results: 150 patients (85.7%) completed 18 months of follow up. IOP was (15.6 ± 5.4) mm Hg at 18 month of post-operation. 135 eyes had an IOP ≤ 21 mm Hg without additional medications, 10 eyes ≥ 21 mm Hg, and the remaining 5 eyes required one or two medications to maintain normal IOP. Using IBAGS system, bleb was graded in 142 eyes as follows: H(0) in 3 eyes, H(1) in 45 eyes, H(2) in 90 eyes, and H(3) in 4 eyes, while V(0) was observed in 66 eyes, V(1-3) in 76 eyes. IOP at 18 months in bleb with microcysts was 2.77 mm Hg lower (β = -2.77, 95%CI = -0.46 to -5.08) than those without microcysts and in bleb with non-vascular was 2.07 mm Hg lower (β = -2.07, 95%CI = -0.15 to -3.98) than those with vascular at 3 months after surgery. IOP was significantly (β = -1.20, 95%CI: -0.00 to -2.40) decreased by 1.2 mm Hg with 10 years of age increase (P < 0.05)., Conclusions: Early filtering bleb with microcysts, vascular, and age are identified as important factors to predict long-term IOP effect in patients with PACG after trabeculectomy but not early morphological appearance of filtering bleb.

Background: Obesity alters breathing mechanics during exercise. Weight loss improves lung function at rest, but the effect of weight loss, especially regional fat loss, on exercise breathing mechanics is unclear. We hypothesized that weight loss, especially a decrease in abdominal fat, would improve breathing mechanics during exercise because of an increase in end-expiratory lung volume (EELV)., Methods: Nine obese men were studied before and after weight loss (13% ± 8% of total fat weight, mean ± SD). Subjects underwent pulmonary function testing, underwater weighing, fat distribution estimates (MRI), and graded cycle ergometry before and after a 12-week diet and exercise program. In seven men, esophageal and gastric pressures were measured. The effects of weight loss were analyzed at rest, at ventilatory threshold (VTh), and during peak exercise by dependent Student t test, and the relationship among variables was determined by correlation analysis., Results: Subjects lost 7.4 ± 4.2 kg of body weight (P < .001), but the distribution of fat remained unchanged. After weight loss, lung volume subdivisions at rest were increased (P < .05) and were moderately associated (P < .05) with changes in chest, waist, and hip circumferences. At VTh, EELV increased, and gastric pressure decreased significantly (P < .05). The changes in waist circumference, hip circumference, BMI, and sum of chest, waist, and hip circumferences were also consistently and significantly correlated (P < .05) with changes in gastric pressure during exercise at VTh., Conclusions: Modest weight loss improves breathing mechanics during submaximal exercise in otherwise healthy obese men, which is clinically encouraging. Improvement appears to be related to the cumulative loss of chest wall fat.

TWIST is an important transcription factor during embryonic development and has recently been found to promote the epithelial-mesenchymal transition (EMT) phenomenon seen during the initial steps of tumor metastasis. To further investigate the potential targets and interacting genes of TWIST in human gastric cancer, we performed microarray analysis to compare the gene expression profiles in HGC-27 cells, with or without small interfering RNA (siRNA)-mediated depletion of TWIST. Our results showed that NF1, RAP1A, SRPX, RBL2, PFDN4, ILK, F2R, ERBB3, and MYB were up-regulated, whereas AKR1C2, FOS, GDF15, NR2F1, ATM, and CTPS were down-regulated after TWIST depletion. Moreover, TWIST-depleted HGC-27 cells showed a reversal of the morphologic and molecular changes associated with EMT. These results provide evidence that TWIST regulates the expression of several genes involved in the differentiation, adhesion, and proliferation of gastric cancer cells. The role of TWIST in the development of certain types of gastric cancer is discussed., ((c) 2008 Wiley-Liss, Inc.)