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BACKGROUND: Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations. METHODS: In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs’ safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs’ relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively. RESULTS: 81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count. CONCLUSIONS: In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Ulcerative colitis (UC), a subtype of inflammatory bowel disease, is characterized by repetitive remission and relapse. Gut microbiome is critically involved in pathogenesis of UC. The shifts in microbiome profile during disease remission remain under-investigated. Recent studies revealed that UC pathogenesis is likely to originate in the mucosal barrier. Therefore, we investigated the effectiveness of mucosal tissue microbiomes to differentiate patients with subclinical UC from healthy individuals. The microbiomes of cecal and rectal biopsies and feces were characterized from 13 healthy individuals and 45 patients with subclinical UC. Total genomic DNA was extracted from the samples, and their microbial communities determined using next-generation sequencing. We found that changes in relative abundance of subclinical UC were marked by a decrease in Proteobacteria and an increase in Bacteroidetes phyla in microbiome derived from rectal tissues but not cecal tissue nor feces. Only in the microbiome of rectal tissue had significantly higher community richness and evenness in subclinical UC patients than controls. Twenty-seven operational taxonomic units were enriched in subclinical UC cohort with majority of the taxa from the Firmicutes phylum. Inference of putative microbial functional pathways from rectal biopsy microbiome suggested a differential increase in interleukin-17 signaling and T-helper cell differentiation pathways. Rectal biopsy tissue was suggested to be more suitable than fecal samples for microbiome assays to distinguish patients with subclinical UC from healthy adults. Assessment of the rectal biopsy microbiome may offer clinical insight into UC disease progression and predict relapse of the diseases.

This paper examines the bifurcation control problem of a class of delayed fractional-order predator-prey models in accordance with an enhancing feedback controller. Firstly, the bifurcation points of the devised model are precisely figured out via theoretical derivation taking time delay as a bifurcation parameter. Secondly, a set comparative analysis on the influence of bifurcation control is numerically studied containing enhancing feedback, dislocated feedback, and eliminating feedback approaches. It can be seen that the stability performance of the proposed model can be immensely heightened by the enhancing feedback approach. At the end, a numerical example is given to illustrate the feasibility of the theoretical results.

Background There is still a lack of data on deep vein thrombosis (DVT) following surgically treated femoral shaft fracture (FSF). The goal of this study was to investigate the characteristics of postoperative DVT and the association between the occurrence of DVT and risk factors in patients undergoing surgical treatment for FSF. Methods This observational retrospective case-control study reviewed 308 patients who received surgical treatment of FSF between January 2016 and October 2020 at a university hospital. Univariate analyses were performed on the data of demographics, comorbidities, laboratory biomarkers, and operation-related indexes. The receiver operating characteristic (ROC) curve analysis, univariate analyses, and multivariate logistic regression analysis were employed to identify the independent risk factors associated with DVT. Results In total, 308 patients with surgically treated FSF were included, among whom 48 (15.6%) patients had postoperative DVTs. The univariate analyses showing significant differences regarding DVT were American Society of Anesthesiologists (ASA) classification, diabetes mellitus, current smoking, aspartate transaminase (AST), and very-low-density lipoprotein (VLDL) level among the 34 factors. According to the ROC results, the optimal cutoff values for intraoperative blood loss, d-dimer, and age were 350 ml, 1.08 μg/ml, and 35 years, respectively. The multivariable model demonstrated 4 significantly independent associations with postoperative DVT, including current smoking, intraoperative blood loss (> 550 ml), age (> 35 years), and d-dimer > 1.09 μg/ml. Conclusion These risk factors as screening tools contribute to risk stratification of the occurrence of thromboembolic events. In addition, our findings would help orthopedic surgeons make a cross-specialty decision and implement targeted precaution measures for patients with FSF.

Background Video-assisted thoracoscopic surgery (VATS) has been widely used for diagnostic wedge resection of lung nodules. When VATS is performed for multiple lung nodules, preoperative localization for each target nodule is required. In this study, we evaluated the clinical effectiveness of computed tomography (CT)-guided simultaneous coil localization in one-stage VATS wedge resection for multiple lung nodules. Methods Between November 2015 to March 2018, 19 patients with multiple target nodules underwent CT-guided simultaneous coil localization and one-stage VATS resection at our center. Data on the technical success of simultaneous localization and wedge resection, complications, and pathological results were collected. Results A total of 43 nodules were localized. The localization was successfully achieved in 42 of 43 nodules (97.7%). The technique of simultaneous localization was successfully achieved in 18 of 19 patients (94.7%). Fifteen patients underwent unilateral lung localization and four patients underwent bilateral lung localization. Three patients (15.8%) experienced asymptomatic pneumothorax after localization. All patients successfully underwent one-stage wedge resection for all target nodules. The mean duration of one-stage VATS procedure was 171.8 ± 84.0 min. The mean volume of blood loss was 94.2 ± 58.0 mL. Three patients experienced pleural effusion after VATS. During a follow-up of 6–31 months (median 18 months), no patient developed new lung nodules or distant metastasis. Conclusions Preoperative simultaneous coil implantation is a safe and simple method for localization of multiple lung nodules. Simultaneous coil localization could effectively guide a one-stage VATS diagnostic wedge resection procedure.

Clinical observations found vision-threatening diabetic retinopathy (DR) occurs in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients, but T1DM may perform more progressive retinal abnormalities at the same diabetic duration with or without clinical retinopathy. In the present study, T1DM and T2DM patients without manifestations of DR were included in our preliminary clinical retrospective observation study to investigate the differentiated retinal function at the preclinical stage. Then, T1DM and T2DM rat models with 12-week diabetic duration were constructed to explore the potential mechanism of the discrepancy in retinal disorders. Our data demonstrated T1DM patients presented a poor retinal function, a higher allele frequency for ALDH2GA/AA, and a depressed aldehyde dehydrogenase 2 (ALDH2) activity and silent information regulator 1 (SIRT1) level, compared to T2DM individuals. In line with this, higher amplitudes of neurovascular function-related waves of electroretinograms were found in T2DM rats. Furthermore, the retinal outer nuclear layers were reduced in T1DM rats. The levels of retinal oxidative stress biomarkers including total reactive oxygen species, NADPH oxidase 4 and mitochondrial DNA damage, and inflammatory indicators covering inducible/endothelial nitric acid synthase ratio, interleukin-1, and interleukin-6 were obviously elevated. Notably, the level of retinal ALDH2 and SIRT1 in T1DM rats was significantly diminished, while the expression of neovascularization factors was dramatically enhanced compared to T2DM. Together, our data indicated that the ALDH2/SIRT1 deficiency resulted in prominent oxidative stress and was in association with DR progression. Moreover, a differentiating ALDH2/SIRT1 expression may be responsible for the dissimilar severity of DR pathological processes in chronic inflammatory-related T1DM and T2DM.

We aim to compare the diagnostic accuracy, safety, and radiation exposure between low-dose and standard-dose computed tomography (CT)-guided cutting needle biopsy (CNB) for lung nodules. From January 2016 to August 2017, all consecutive patients admitted with lung nodule underwent low-dose or standard-dose CT-guided CNB procedure in our center. Diagnostic accuracy and radiation dose were compared. A total of 67 and 69 patients who underwent low-dose and standard-dose CT-guided CNB procedure were included in this study. Each patient underwent CT-guided CNB for 1 nodule. The technical success rates were 100% in both groups. The sensitivity, specificity, and overall diagnostic accuracy were 97.7%, 100%, and 98.5% for low-dose group and 91.5%, 100%, and 94.2% for standard-dose group. There was no significant difference in diagnostic accuracy (P = .380) between 2 groups. Pneumothorax was found in 8 and 15 patients in the low-dose and standard-dose groups, respectively (11.9% vs 21.7%, P = .127). Hemoptysis was found in 10 and 10 patients in the low-dose and standard-dose groups, respectively (14.9% vs 14.5%, P = .943). The mean dose-length product was 38.2 ± 17.2 mGy-cm and 375.3 ± 115.7 mGy-cm in the low-dose and standard-dose groups (P

Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1β in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.

Background: Salvia miltiorrhiza is a medical herb for human disorders including cardiovascular diseases and cancer. However, the interactions between Salvia miltiorrhiza and its endophytes are largely unknown. The current study aimed at identifying its endophytic fungi and examining their inhibitory effects on anti-pathogenic fungus. Materials and Methods: Distinct species of endophytic fungi were isolated from the roots of Salvia miltiorrhiza, cultured, sequenced, aiming to predict their taxonomical structures. Meanwhile, extracts from each endophytic fungus fermentations were isolated, compared and evaluated on the inhibitory efficacies on five pathological fungi, Cercospora nicotianae, Phoma arachnidicola, Staphylococcus, Phytophthora eggplant, and Rhizoctonia cerealis. Results: A total of 34 strains of endophytic fungi were obtained from Salvia miltiorrhiza. Among them, SX19 and C. Gloeosporioids exhibited the most effective inhibitions on five pathogenic fungi. Conclusion: The anti-fungal activities of the endophytic fungus from Salvia miltiorrhiza were confirmed for the first time, and this may benefit crop quality and production in the future.

Laparoscopic pancreaticoduodenectomy (LPD) is widely used as a treatment for periampullary tumors and pancreatic head tumors. However, postoperative pancreatic fistula (POPF), which significantly affects mortality and length of hospital stay of patients, remains one of the most common and serious complications following LPD. Though numerous technical modifications for pancreaticojejunostomy (PJ) have been proposed, POPF is still the “Achilles heel” of LPD. To reduce POPF rate and other postoperative complications following LPD by exploring the best approach to manage with the pancreatic remnant, a novel duct-to-mucosa anastomosis technique named Double Layer Running Suture (Double R) for the PJ was established. During 2018 and 2020, a totally 35 patients who underwent LPD with Double R were included, data on the total operative time, PJ duration, estimated blood loss, recovery of bowel function, postoperative complications, and length of hospital stay were collected and analyzed. The average duration of surgery was (380 ± 69) minutes. The mean time for performing PJ was (34 ± 5) minutes. The average estimated blood loss was (180 ± 155) mL. The overall POPF rate was 8.6% (3/35), including 8.6% (3/35) for the biochemical leak, 0% (0/35) for Grade B, and 0% (0/35) for Grade C. No patient suffered from biliary fistula, post-pancreatectomy hemorrhage, and intra-abdominal infection, the 30-day mortality was 0%. Double R anastomosis is potentially a safe, reliable, and rapid anastomosis with a low rate of POPF and post-pancreatectomy hemorrhage. It provides surgeons more options when performing LPD. However, its safety and effectiveness should be verified further by a larger prospective multicenter study.

Background: Published trials reported that high-energy extracorporeal shock wave therapy (HEEPSWT) can effectively treat early stage femoral head osteonecrosis (ESFHO). However, their results are still inconsistent. Thus, this study will systematically and comprehensively explore the effectiveness and safety of HEEPSWT for ESFHO. Methods: We will retrieve the electronic databases of Cochrane Library, EMBASE, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, VIP database, and China National Knowledge Infrastructure from inception to the present. All randomized controlled trials that focusing on the effectiveness and safety of HEEPSWT for ESFHO will be considered. Two researchers will undertake literature selection, information collection, and risk of bias evaluation separately. If disagreements occur, we will invite a third researcher for consultation and a final decision will be made. Cochrane risk of bias tool, and Grades of Recommendation, Assessment, Development and Evaluation will be utilized to assess the risk of bias and quality of evidence, respectively. We will perform statistical analysis using RevMan 5.3 software. Results: This study will provide a detailed summary of exist evidence related to the effectiveness and safety of HEEPSWT for ESFHO. Conclusion: The results of this study synthesize the evidence regarding the HEEPSWT for ESFHO, which may help to guide clinical management in the future. Systematic review registration: INPLASY202060055.

Background In March 2020, the WHO declared the novel coronavirus outbreak a global pandemic. While great success in coronavirus disease 2019 (COVID-19) control has been achieved in China, imported cases have become a major challenge. This study aimed to describe the epidemiological and clinical characteristics of imported COVID-19 cases and to assess the effectiveness of screening strategies in Beijing, China. Methods This retrospective study included all imported cases transferred to Beijing Ditan Hospital from 29 February to 20 March 2020 who were screened by both chest computed tomography (CT) and reverse-transcriptase-polymerase chain reaction (RT-PCR) at the initial presentation. Demographic, clinical and laboratory data, in addition to chest CT imaging, were collected and analysed. Results In total, 2545 cases were included, among which 71 (2.8%) were finally diagnosed with laboratory-confirmed COVID-19. The majority 63 (88.7%) were from Europe. The most common initial symptoms were cough and fever, which accounted for 49.3% and 42.3%, respectively. Only four cases (5.6%) had lymphocytopenia, and thirteen cases (18.3%) demonstrated elevated levels of C-reactive protein (CRP). All cases had normal serum levels of procalcitonin (PCT). At initial presentation, among the 71 confirmed cases, 59 (83.1%) had a positive RT-PCR assay, and 35 (49.3%) had a positive chest CT. Twelve (16.9%) had a negative RT-PCR assay but a positive chest CT. Conclusions A combination of RT-PCR and chest CT is an effective strategy for the screening of imported COVID-19 cases. Our findings provide important information and clinical evidence about the infection control of imported COVID-19 cases.

We determined the clinical effectiveness and long-term outcomes in patients with distal biliary obstruction (DBO) secondary to pancreatic carcinoma (PC) who were treated by self-expanded metallic stent (SEMS) insertion with or without high-intensity focused ultrasound (HIFU) ablation. From January 2014 to December 2018, consecutive patients with DBO secondary to PC underwent SEMS insertion with or without HIFU ablation in our center. The long-term outcomes were compared between the 2 groups. During the included period, 75 patients underwent SEMS insertion with (n = 34) or without (n = 41) HIFU ablation in our center. SEMS insertion was successfully performed in all patients. Liver function was significantly improved after SEMS insertion in both groups. An average of 2.9 HIFU treatment sessions per patient were performed. Twenty patients (stent + HIFU group: 7; stent-only group: 13) experienced stent dysfunction (P = .278). The clinical response rate to HIFU ablation was 79.4%. The median stent patency was significantly longer in the stent with HIFU group than in the stent-only group (175 vs 118 days, P = .005). The median survival was significantly longer in the stent with HIFU group compared with the stent-only group (211 versus 136 days, P = .004). An Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 (hazard ratio: 0.300; P = .002) and subsequent HIFU ablation (hazard ratio: 0.508; P = .005) were associated with prolonged survival. HIFU ablation following stent insertion can prolong the stent patency and survival for patients with DBO secondary to PC.

The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.

The aim of this study was to evaluate the safety and clinical effectiveness of endovascular stent repair of celiac arterial aneurysm (CAA). From January 2015 to December 2018, 11 patients (7 males, 4 females with a mean age of 52.2 ± 7.9 years) underwent endovascular stent repair of CAA in our center. A covered stent was used to occlude the CAA neck. Follow-up was performed 2 weeks and 1, 3, 6, and 12 months following surgery and yearly thereafter. Rates of technical success, treatment-related complications, and long-term outcome were analyzed. Each patient was placed with 1 stent for repair of CAA. Stent was placed in the celiac and common hepatic arteries for 10 patients and was placed in the celiac artery for 1 patient. The duration of the procedure ranged from 50 to 75 minutes (mean 63.2 ± 7.2 minutes). The rate of technical success of the endovascular stent repair was 100%. No patient experienced CAA rupture or instant endoleak during or after stent insertion. Abdominal pain was relieved progressively after stent insertion. All patients were followed-up for 6 to 48 months (mean 22.4 ± 10.8 months). All patients were alive during the follow-up. No endoleaks were experienced during follow-up with 100% stent patency rate. No patient suffered splenic, hepatic, or bowel infarction during follow-up. Endovascular stent repair is a safe, simple, and effective treatment for patients with CAA.

The data presented in this article are related to the research article entitled “Pollen spectrum, a cornerstone for tracing the evolution of the eastern central Asian desert” (JQSR 5260) (Lu et al., 2018) [1] In this paper, we supply a dataset, which provides a descriptive and general summary of pollen characteristic of desert dominant species in the eastern arid central Asia (ACA). The other important component is the illustration on pollen grains traits under light microscopy (LM) and scanning electron microscopy (SEM). Pollen grains of 56 species are extracted from voucher specimens from the PE herbarium at the Institute of Botany. It is worth noting that these species own special distribution patterns in China. The distribution maps are plotted using the Google Maps and the species distribution data at the county level supplied by the Chinese Virtual Herbarium (http://www.cvh.ac.cn/). Keywords: Arid central Asia, Desert vegetation, Pollen morphological traits, Temperate desert

Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9+ basal cells (BCs) located at airway epithelium rugae can regenerate adult human lung. Human SOX9+ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient’s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3–12 months after cell transplantation. Altogether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future. Electronic supplementary material The online version of this article (10.1007/s13238-018-0506-y) contains supplementary material, which is available to authorized users.

Background: This study aims to systematically explore the efficacy and safety of mometasone furoate (MTF) for patients with nasal polyps (NP). Methods: We will search MEDLINE, Cochrane Library, PubMed, Springer, Web of Science, Ovid, Wangfang and Chinese Biomedical Literature Database from their inception to April 30, 2019 without language restrictions. All randomized controlled trials (RCTs) of MTF for the treatment of NP will be considered for inclusion. RevMan 5.3 software will be used for data synthesis, subgroup analysis, sensitivity analysis, as well as the meta-analysis. Results: Primary outcomes include change in symptom scores (as measured by any symptom scores), and polyp size (as assessed by any Polyp size scores or tools). Secondary outcomes consist of polyp recurrence, change in nasal air flow, quality of life outcomes (as measured by any quality of life scales, such as Short Form Health Survey is a 36-item), and adverse events. Conclusion: This study will provide evidence for judging whether MTF is an effective and safe treatment for NP or not. PROSPERO registration number: PROSPERO CRD42019134037.

The present study sought to assess the feasibility and effectiveness of double stent insertion as a means of managing combined malignant airway and superior vena cava (SVC) obstruction (CMASO). From July 2010 to January 2018, twelve consecutive patients with CMASO were treated by double stent insertion (airway and SVC stents) in our centers. We assessed data pertaining to both technical and clinical success rates, as well as to long-term patient outcomes. The use of double stents (12 airway stents and 19 SVC stents) was technically successful in all study subjects, with a 0 to 92 days period between the 2 stent insertions (mean 27.8 days). Patients did not show evidence of any procedure-related complications. Mean patient Hugh-Jones grades improved from 4.4 ± 0.5 before inserting the airway stent down to 1.2 ± 0.4 following this insertion (P

Background Around the Cretaceous-Paleogene (K-Pg) boundary, an obvious global cooling occurred, which resulted in dramatic changes in terrestrial ecosystems and the evolutionary trends of numerous organisms. However, how plant lineages responded to the cooling has remained unknown until now. Between ca. 70–60 Ma Mesocyparis McIver & Basinger (Cupressaceae), an extinct conifer genus, was distributed from eastern Asia to western North America and provides an excellent opportunity to solve this riddle. Results Here we report a new species, Mesocyparis sinica from the early Paleocene of Jiayin, Heilongjiang, northeastern China. By integrating lines of evidence from phylogeny and comparative morphology of Mesocyparis, we found that during ca.70–60 Ma, the size of seed cone of Mesocyparis more than doubled, probably driven by the cooling during the K-Pg transition, which might be an effective adaptation for seed dispersal by animals. More importantly, we discovered that the northern limit of this genus, as well as those of two other arboreal taxa Metasequoia Miki ex Hu et Cheng (gymnosperm) and Nordenskioldia Heer (angiosperm), migrated ca.4–5° southward in paleolatitude during this time interval. Conclusions Our results suggest that the cooling during the K-Pg transition may have been responsible for the increase in size of the seed cone of Mesocyparis and have driven the migration of plants southwards.

Eosinophil asthma is characterized by the infiltration of eosinophils to the bronchial epithelium. The toxic cationic protein released by eosinophils, mainly major basic protein (MBP), is one of the most important causative factors of epithelium damage. Poly-L-Arginine (PLA) is a kind of synthetic cationic polypeptides, which is widely used to mimic the effects of MBP on epithelial cells in vitro. However, little is known about the changes of differentially expressed genes (DEGs) and transcriptome profiles in cationic protein stimulated epithelial cells. In this study, we compared the expression of DEGs and transcriptome profiles between PLA-treated airway epithelial cells NCI-H292 and control. The results showed that there were a total of 230 DEGs, of which 86 were upregulated and 144 were downregulated. These DEGs were further analyzed using gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results showed that the upregulated DEGs were involved in cholesterol synthesis, protein binding, and composition of cellular membranes, mainly enriched in metabolic and biosynthesis pathways. While downregulated DEGs were implicated in cell adhesion, extracellular matrix (ECM) composition and cytoskeleton and were enriched in ECM pathway. In conclusion, our research provided the mechanism of the cationic polypeptides acting on the airway epithelial cells on the basis of transcriptomic profile, and this could be regarded as important indications in unveiling the pathologic role of natural cationic proteins in the damage to epithelial cells of asthmatics.

To evaluate the feasibility, local control, and survival after computed tomography (CT)-guided cryoablation for adrenal metastases. This study included 31 consecutive patients with adrenal metastases who were treated by CT-guided cryoablation in our center from July 2011 to October 2017. The technical success rate, local progression rate, local progression-free survival (LPFS), systemic progression-free survival (SPFS), and overall survival were assessed. The predictors of survival were determined using univariate and multivariate Cox regression analyses. The primary and secondary technical success rates were 90.3% and 100%, respectively. None of the patients experienced a hypertensive crisis. The local progression rate during follow-up was 19.4%. Systemic progression was found in 9 patients. The cumulative 1-, 3-, and 5-year LPFS rates were 80.6%, 37.8%, and 18.4%, respectively. The cumulative 1-, 3-, and 5-year SPFS rates were 77.4%, 31.9%, and 14.6%, respectively. The cumulative 1-, 3-, and 5-year overall survival rates were 83.9%, 45.0%, and 30.0%, respectively. The existence of an extra-adrenal tumor was a significant independent predictor of worse overall survival (P = .012). The mean overall survival durations were significantly different between patients with and without an extra-adrenal tumor (16.6 ± 2.4 vs 50.9 ± 4.5 months, P

We examined the therapeutic effects of argon-helium cryoablation guided by computed tomography (CT) in the treatment of sacral chordoma. This is a retrospective study. CT-guided argon-helium cryoablation was used to treat 9 sacral chordoma patients at our centers between January 2016 and June 2019. We collected data on treatment response and success. Data from long-term follow-up of treatment outcomes were also assessed. All patients were treated successfully according to the indicated technical parameters. There were no reports of procedure-related complications from any of the patients. Complete response (CR) was also achieved in all patients. Six patients (66.7%) achieved initial CR after 1 treatment session and 3 patients (33.3%) achieved secondary CR after 2 treatment sessions. The chordoma-related symptoms improved significantly in all patients after treatment. The mean visual analogue scale score improved from 7.3 before treatment to 4.2 after treatment (P

Objective. The aim of our study was to investigate the expression of EGFR and PTEN in tissues and measure the serum platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) to evaluate the prognostic factors of patients with epithelioid malignant peritoneal mesothelioma (MPeM). Methods. 33 patients of pathologically diagnosed epithelioid MPeM tissues were analyzed using immunohistochemistry to detect EGFR and PTEN; the PLR and NLR were determined by using a routine blood test. We analyzed the relationships of these markers to age, sex, asbestos exposure, elevated platelet count, ascites, and clinical stage. Results. EGFR and PTEN expressions were positive in 22 (66.67%) and 7 (21.21%) epithelioid MPeM patients, respectively. However, these two markers as well as PLR and NLR were not significantly associated with age, sex, asbestos exposure, elevated platelet counts, ascites, and clinical stage (P>0.05). The correlation between EGFR and PTEN was negative (r=−0.577, P<0.001), but the correlation between NLR and PLR was positive (r=0.456, P=0.008). The median survival of all patients was 6 months. In univariate analysis, PTEN (P<0.001), PLR (P=0.014), and NLR (P=0.015) affected the overall survival. Multivariate analysis revealed that PTEN and PLR were validated as predictive for overall survival of epithelioid MPeM (HR=0.070, P=0.001, and HR=3.379, P=0.007, respectively). Conclusion. On the basis of these results, it is suggested that PTEN and PLR are risk factors for the prognosis of epithelioid MPeM, which may be targets for selective therapies and improve the outcomes of patients with epithelioid MPeM.

Introduction: Spontaneous cerebrospinal fluid leakage is usually caused by developmental abnormalities and is rare, accounting for approximately 5% of the cases of cerebrospinal fluid (CSF) leakage.[1] To the best of our knowledge, clival dysplasia-caused CSF rhinorrhea has never been reported in the neurosurgical field. Conclusion: Spontaneous cerebrospinal fluid rhinorrhea is often treated by surgery, and a transsphenoidal approach repair is the main surgical method used, offering the advantages of less trauma, fewer complications, rapid postoperative recovery, and low recurrence rate.

Background Lin28B and its paralog Lin28A are small RNA binding proteins that have similar inhibitory effects, although they target separate steps in the maturation of let-7 miRNAs in mammalian cells. Because Lin28B participates in the promotion and development of tumors mostly by blocking the let-7 tumor suppressor family members, we sought to explore the associated mechanisms to gain insights into how Lin28B might be decreased in human cancer cells to increase let-7 levels and reverse malignancy. Results We demonstrated that the histone acetyltransferase PCAF, via its cold shock domain, directly interacts with and subsequently acetylates Lin28B in lung adenocarcinoma-derived H1299 cells. RT-qPCR assays showed that both let-7a-1 and let-7g were increased in PCAF-transfected H1299 cells. Lin28B is acetylated by ectopic PCAF and translocates from the nucleus to the cytoplasm in H1299 cells. Conclusions The effects of acetylated Lin28B on let-7a-1 and let-7g are similar to that of stable knockdown of Lin28B in H1299 cells. The new role of PCAF in mediating Lin28B acetylation and the specific release of its target microRNAs in H1299 cells may shed light on the potential application of let-7 in the clinical treatment of lung cancer patients.

The pygmy killer whale (Feresa attenuata) (PKW) is a tropical and subtropical marine mammal commonly found in the Atlantic, Indian and Pacific oceans. Since the PKWs live in offshore protected territories, they are rarely seen onshore. Hence, PKW are one of the most poorly understood oceanic species of odontocetes. The dermal tissue comes primarily from stranding events that occur along the coast of the Shantou, Guangdong, China. The sampled tissues were immediately processed and attached on collagen-coated 6-well tissue culture plate. The complete medium (DMEM and Ham’s F12, fetal bovine serum, antibiotic and essential amino acids) was added to the culture plates. The primary culture (PKW-LWH) cells were verified as fibroblast by vimentin and karyotype analyses, which revealed 42 autosomes and two sex chromosomes X and Y. Following transfection of PKW-LWH cells with a plasmid encoding, the SV40 large T-antigens and the transfected cells were isolated and expanded. Using RT-PCR, western blot, immunofluorescence analysis and SV40 large T-antigen stability was confirmed. The cell proliferation rate of the fibroblast cells, PKW-LWHT was faster than the primary cells PKW-LWH with the doubling time 68.9h and 14.4h, respectively. In this study, we established PKW dermal fibroblast cell line for the first time, providing a unique opportunity for in vitro studies on the effects of environmental pollutants and pathogens that could be determined in PKW and/or Cetaceans.

The goal of this study is to determine the feasibility, diagnostic accuracy, and risk factor of complications of computed tomography (CT)-guided percutaneous cutting needle biopsy (PCNB) for small lung nodules. From January 2014 to May 2015, 141 patients with small lung nodule were performed with CT-guided PCNB procedure. Data on technical success, diagnostic accuracy, and complication were collected and analyzed. Technical success of CT-guided PCNB for small lung nodules was 100%. A total of 141 nodules were punctured. The mean time of the procedure was 15.7 ± 4.3 minutes. The PCNB results included malignancy (n = 79), suspected malignancy (n = 6), specific benign lesion (n = 8), nonspecific benign lesion (n = 47), and invalid diagnosis (n = 1). The final diagnosis of the 141 nodules included malignancy (n = 90), benign (n = 37), and nondiagnostic lesion (n = 14). The nondiagnostic nodules were not included for calculating the diagnostic accuracy. The sensitivity, specificity, and overall diagnostic accuracy of CT-guided PCNB for small lung nodule were 94.4% (85/90), 100% (37/37), and 96.1% (122/127), respectively. Pneumothorax and lung hemorrhage (≥ grade 2) occurred in 17 (12.1%) and 22 (15.6%) patients, respectively. Based on the univariate and multivariate logistic analyses, the risk factors of pneumothorax included nonprone position (P = .019) and longer procedure time (P = .018). The independent risk factor of lung hemorrhage (≥ grade 2) was deeper lesion distance from pleura along needle path (P = .024). This study demonstrates that CT-guided PCNB can provide a high diagnostic accuracy for small lung nodule with acceptable complications.

The inherent stochasticity generates substantial gene expression variation among isogenic cells under identical conditions, which is frequently referred to as gene expression noise or cell-to-cell expression variability. Similar to (average) expression level, expression noise is also subject to natural selection. Yet it has been observed that noise is negatively correlated with expression level, which manifests as a potential constraint for simultaneous optimization of both. Here, we studied expression noise in human embryonic cells with computational analysis on single-cell RNA-seq data and in yeast with flow cytometry experiments. We showed that this coupling is overcome, to a certain degree, by a histone modification strategy in multiple embryonic developmental stages in human, as well as in yeast. Importantly, this epigenetic strategy could fit into a burst-like gene expression model: promoter-localized histone modifications (such as H3K4 methylation) are associated with both burst size and burst frequency, which together influence expression level, while gene-body-localized ones (such as H3K79 methylation) are more associated with burst frequency, which influences both expression level and noise. We further knocked out the only “writer” of H3K79 methylation in yeast, and observed that expression noise is indeed increased. Consistently, dosage sensitive genes, such as genes in the Wnt signaling pathway, tend to be marked with gene-body-localized histone modifications, while stress responding genes, such as genes regulating autophagy, tend to be marked with promoter-localized ones. Our findings elucidate that the “division of labor” among histone modifications facilitates the independent regulation of expression level and noise, extend the “histone code” hypothesis to include expression noise, and shed light on the optimization of transcriptome in evolution., Author summary Gene expression noise, or cell-to-cell expression variability, has been a topic of intense interest for more than a decade. The prevailing model of “burst-like transcription” mediated by the promoter transitions between on and off states explains the formation of noise in eukaryotes. Albeit widely accepted, the cis- elements that determine the burst frequency and burst size remain largely unknown. Here we systematically examined the relationship between transcriptional burst frequency/size and all major histone modifications in various cell types, including human embryonic cells, mouse embryonic stem cells, and yeast, and found that histone markers can be divided into two groups based on their associations with burst frequency/ size. Coincidently, promoter-localized histone markers are associated with both burst size and burst frequency whereas gene-body-localized ones are more associated with burst frequency. We further knocked out a gene that is responsible for “writing” a gene-body histone mark in yeast, and found that burst frequency is indeed reduced. Our findings reveal a new mechanism of transcriptional burst regulation and shed light on the simultaneous optimization of gene expression level and noise in evolution.

This meta-analysis was performed to evaluate the effect of cognitive behavioural therapy (CBT) in improving the depression symptoms of patients with diabetes. Literature search was conducted in PubMed and Embase up to October 2016 without the initial date. The pooled SMD (standard mean difference) and its 95% confidence interval (CI) were calculated by Revman 5.3. Subgroup analyses were performed by type of diabetes and evaluation criteria of depression. A total of five randomized control trials involving 834 patients with diabetes mellitus (including 417 patients in CBT group and 417 patients in control group) were included in this meta-analysis. The pooled estimates indicated significant improvement of depression by CBT compared with routine approaches in overall outcomes (SMD =–0.33, 95% CI =–0.46 to –0.21, P

Purpose Diabetic retinopathy (DR) is a leading cause of vision loss in working-age people. To retard the development and progression of retina lesions, effective therapeutic strategies directed toward key molecular targets are desired. Phlorizin is effective in treating diabetic complications, but little is known about functional protein changes that may mediate its actions. The aim of this study was to identify retinal proteomic alterations in db/db mice treated with phlorizin. Methods We used C57BLKS/J db/db mice as a type 2 diabetic animal model, while C57BLKS/J db/m mice were selected as the control. Phlorizin (20 mg/kg bodyweight /d) was administrated to db/db mice for ten weeks. Serum fasting blood glucose and advanced glycation end products were determined. Meanwhile, retina cell apoptosis was determined with terminal transferase dUTP nick end labeling. Isobaric tags for relative and absolute quantification and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to identify and profile retinal proteins among control, untreated diabetic, and phlorizin-treated db/db mice. The expression of glial fibrillary acidic protein was measured in retinas using western blotting analysis. Results Phlorizin treatment significantly reduced fasting blood glucose and levels of advanced glycation end products (p

Despite the prevalence of intron losses during eukaryotic evolution, the selective forces acting on them have not been extensively explored. Arabidopsis thaliana lost half of its genome and experienced an elevated rate of intron loss after diverging from A. lyrata. The selective force for genome reduction was suggested to have driven the intron loss. However, the evolutionary mechanism of genome reduction is still a matter of debate. In this study, we found that intron-lost genes have high synonymous substitution rates. Assuming that differences in mutability among different introns are conserved among closely related species, we used the nucleotide substitution rate between orthologous introns in other species as the proxy of the mutation rate of Arabidopsis introns, either lost or extant. The lost introns were found to have higher mutation rates than extant introns. At the genome-wide level, A. thaliana has a higher mutation rate than A. lyrata, which correlates with the higher rate of intron loss and rapid genome reduction of A. thaliana. Our results indicate that selection to minimize mutational hazards might be the selective force for intron loss, and possibly also for genome reduction, in the evolution of A. thaliana. Small genome size and lower genome-wide intron density were widely reported to be correlated with phenotypic features, such as high metabolic rates and rapid growth. We argue that the mutational-hazard hypothesis is compatible with these correlations, by suggesting that selection for rapid growth might indirectly increase mutational hazards.

Background: Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. Methods: PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Results: Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98–1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90–1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94–1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23–0.94; P = 0.032). Conclusion: Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers.

Thuja, a genus of Cupressaceae comprising five extant species, presently occurs in both East Asia (3 species) and North America (2 species) and has a long fossil record from Paleocene to Pleistocene in the Northern Hemisphere. Two distinct hypotheses have been proposed to account for the origin and present distribution of this genus. Here we recognize and describe T. sutchuenensis Franch., a new fossil Thuja from the late Pliocene sediments of Zhangcun, Shanxi, North China, based on detailed comparisons with all living species and other fossil ones, integrate the global fossil records of this genus plotted in a set of paleomaps from different time intervals, which show that Thuja probably first appeared at high latitudes of North America in or before the Paleocene. This genus reached Greenland in the Paleocene, then arrived in eastern Asia in the Miocene via the land connection between East Asia and western North America. In the late Pliocene, it migrated into the interior of China. With the Quaternary cooling and drying, Thuja gradually retreated southwards to form today’s disjunctive distribution between East Asia and North America.

Modern pollen records have been used to successfully distinguish between specific prairie types in North America. Whether the pollen records can be used to detect the occurrence of Eurasian steppe, or even to further delimit various steppe types was until now unclear. Here we characterized modern pollen assemblages of meadow steppe, typical steppe and desert steppe from eastern Eurasia along an ecological humidity gradient. The multivariate ordination of the pollen data indicated that Eurasian steppe types could be clearly differentiated. The different steppe types could be distinguished primarily by xerophilous elements in the pollen assemblages. Redundancy analysis indicated that the relative abundances of Ephedra, Tamarix, Nitraria and Zygophyllaceae were positively correlated with aridity. The relative abundances of Ephedra increased from meadow steppe to typical steppe and desert steppe. Tamarix and Zygophyllaceae were found in both typical steppe and desert steppe, but not in meadow steppe. Nitraria was only found in desert steppe. The relative abundances of xerophilous elements were greater in desert steppe than in typical steppe. These findings indicate that Eurasian steppe types can be differentiated based on recent pollen rain.

The aim was to investigate the effects of theGABABreceptor antagonist, CGP46381, on form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25). The deprived eyes were treated with daily subconjunctival injections (100 μl) of either 2% CGP46381, 0.2% CGP46381, or saline or received no injection. The fellow eyes were left untreated. Another six animals received no treatment. At the start and end of the treatment period, ocular refractions were measured using retinoscopy and vitreous chamber depth (VCD) and axial length (AL) using A-scan ultrasound. All of the deprived eyes developed relative myopia (treated versus untreated eyes,P<0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA,P<0.0001). The highest dose tested, 2% CGP46381, significantly inhibited myopia development compared to saline (2% CGP46381: −1.08 ± 0.40 D, saline: −4.33 ± 0.67 D,P<0.01). The majority of these effects were due to less AL (2% CGP46381: 0.03 ± 0.01 mm, saline: 0.13 ± 0.02 mm,P<0.01) and VCD (2% CGP46381: 0.02 ± 0.01 mm, saline: 0.08 ± 0.01 mm,P<0.01) elongation. The lower dose tested, 0.2% CGP46381, did not significantly inhibit FDM (P>0.05). Subconjunctival injections of CGP46381 inhibit FDM development in guinea pigs in a dose-dependent manner.

Phosphorylation of histone demethylase KDM3A in response to thermal stress enables its specific recruitment to target genes by Stat1., Histone lysine (K) residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from specific K residues in histones. KDM3A (also known as JHDM2A or JMJD1A) is an H3K9me2/1 demethylase. KDM3A performs diverse functions via the regulation of its associated genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanism by which the activity of KDM3A is regulated is largely unknown. Here, we demonstrated that mitogen- and stress-activated protein kinase 1 (MSK1) specifically phosphorylates KDM3A at Ser264 (p-KDM3A), which is enriched in the regulatory regions of gene loci in the human genome. p-KDM3A directly interacts with and is recruited by the transcription factor Stat1 to activate p-KDM3A target genes under heat shock conditions. The demethylation of H3K9me2 at the Stat1 binding site specifically depends on the co-expression of p-KDM3A in the heat-shocked cells. In contrast to heat shock, IFN-γ treatment does not phosphorylate KDM3A via MSK1, thereby abrogating its downstream effects. To our knowledge, this is the first evidence that a KDM can be modified via phosphorylation to determine its specific binding to target genes in response to thermal stress., Author Summary Histone methylation regulates gene expression and can have drastic consequences for health if the process is defective. Histone lysine demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from histones. KDM3A is a H3K9me2/1 demethylase that performs diverse functions via the regulation of its target genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanisms underlying KDM3A regulation of specific genes at specific times are largely unknown. Here we found that a physiological stress—elevated temperature—induces KDM3A phosphorylation in human cells via the MSK1 kinase. This phosphorylated form of KDM3A directly interacts with the transcription factor Stat1, which enables Stat1 to recruit KDM3A to Stat1-binding sequences at the promoters of specific target genes. KDM3A then acts to demethylate H3K9me2/1 at these targets, thereby causing specific gene expression in response to the thermal stress. We conclude that heat shock can affect the expression of many genes in human cells via a novel activation mechanism that is centered around the phosphorylation of KDM3A.

Purpose. To determine interfractional changes of lung tumor centroid position and tumor regression during stereotactic body radiation therapy (SBRT).Methods and Materials. 34 patients were treated by SBRT in 4-5 fractions to a median dose of 50 Gy. The CT scans acquired for verification were registered with simulation CT scans. The gross target volume (GTV) was contoured on all verification CT scans and compared to the initial GTV in treatment plan system.Results. The mean (±standard deviation, SD) three-dimension vector shift was5.2±3.1 mm. The mean(±SD)interfractional variations of tumor centroid position were-0.7±4.5 mm in anterior-posterior (AP) direction,0.2±3.1 mm in superior-inferior (SI) direction, and0.4±2.4 mm in right-left (RL) direction. Large interfractional variations (≥5 mm) were observed in 5 fractions (3.3%) in RL direction, 16 fractions (10.5%) in SI direction, and 36 fractions (23.5%) in AP direction. Tumor volume did not decrease significantly during lung SBRT.Conclusions. Small but insignificant tumor volume regression was observed during lung SBRT. While the mean interfractional variations of tumor centroid position were minimal in three directions, variations more than 5 mm account for approximately a third of all, indicating additional margin for PTV, especially in AP direction.

The Hengduan Mountains, with a distinct altitudinal differentiation and strong vertical vegetation zonation, occupy an important position in southwestern China as a global hotspot of biodiversity. Pollen analysis of lake sediments sampled along an altitudinal gradient in this region helps us to understand how this vegetation zonation arose and how it has responded to climate change and human impacts through time. Here we present a ~30-ka pollen record and interpret it in terms of vegetational and climatic change from a 310 cm-long core from Shudu Lake, located in the Hengduan Mountains region. Our results suggest that from 30 to 22 cal. ka BP, the vegetation was dominated by steppe/grassland (comprising mainly Artemisia, Poaceae and Polygonaceae) and broad-leaved forest (primarily Quercus, Betula and Castanopsis) in the lake catchment, reflecting a relatively warm, wet climate early in this phase and slightly warmer, drier conditions late in the phase. The period between 22 and 13.9 cal. ka BP was marked by a large expansion of needle- and broad-leaved mixed forest (Pinus, Abies and Quercus) and a decline in the extent of steppe/grassland, indicating warming, drying climatic conditions followed by a cold, wet period. Between 13.9 and 3 cal. ka BP, steppe/grassland expanded and the area covered by needle- and broad-leaved mixed forest reduced, implying a fluctuating climate dominated by warm and humid conditions. After 3 cal. ka BP, the vegetation was characterized by an increase in needle-leaved forest and reduction in steppe/grassland, suggesting warming and drying climate. A synthesis of palynological investigations from this and other sites suggests that the vegetation succession patterns seen along an altitudinal gradient in northwestern Yunnan since the Late Pleistocene are comparable, but that each site has its own characteristics probably due to the influences of altitude, topography, microclimate and human impact.

Background Omega-3 fatty acids are known to prevent cardiac death. However, previous observational studies have suggested that omega-3 fatty acids are associated with cancer risk in adults. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of omega-3 fatty acids on the risk of cancer incidence, nonvascular death, and total mortality. Methods In February 2013, we performed electronic searches in PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials on cancer incidence, nonvascular death, and total mortality. Relative risk (RR) was used to measure the effect of omega-3 fatty acid supplementation on the risk of cancer incidence, nonvascular death, and total mortality using a random-effect model. The analysis was further stratified by factors that could affect the treatment effects. Results Of the 8,746 identified articles, we included 19 trials reporting data on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439 events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97–1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93–1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88–1.03; P = 0.24) when compared to a placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was associated with a reduction in total mortality risk if the proportion of men in the study population was more than 80%, or participants received alpha-linolenic acid. Conclusions Omega-3 fatty acid supplementation does not have an effect on cancer incidence, nonvascular death, or total mortality.

Background.The prognostic significance of COX2 for survival of patients with oral cancer remains controversial. Thus, the meta-analysis was performed in order to identify COX2 expression impact on prognosis of oral cancer.Method.Relevant literatures were searched using the following electronic databases without any language restrictions: Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and CBM. Version 12.0 STATA software (Stata Corporation, College Station, Texas, USA) was used for the current meta-analysis. Odds ratios (ORs) and hazard ratios (HRs) with their corresponding 95% confidence interval (95% CI) were also calculated to clarify the correlation between COX2 expression and prognosis of oral cancer.Results.Final analysis of 979 oral cancer patients from 12 clinical cohort studies was performed. The meta-analysis results show that COX2 expression in cancer tissues was significantly higher than those in normal and benign tissues (allP< 0.05). Combined HR of COX2 suggests that positive COX2 expression has a shorter overall survival (OS) than those of negative COX2 expression (P< 0.05).Conclusion.The meta-analysis study shows that elevated COX2 expression may be associated with the pathogenesis of oral cancer and with a worse prognosis in oral cancer patients.

Background Studies have reported inconsistent results for the existence of an association between polyunsaturated fatty acid (PUFA) intake and risk of lung cancer. The purpose of this study is to summarize the evidence regarding this relationship using a dose response meta-analytic approach. Methodology and Principal Findings We searched the PubMed, EmBase, and Cochrane Library electronic databases for related articles published through July 2013. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were included. We did random-effects meta-analyses of study-specific incremental estimates to determine the risk of lung cancer associated with a 5 g per day increase in PUFA intake. Overall, we included 8 prospective cohort studies reporting data on 1,268,442 individuals. High PUFA intake had little or no effect on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78–1.06; P = 0.230). Furthermore, the dose-response meta-analysis also suggested that a 5 g per day increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98; 95%CI: 0.96–1.01; P = 0.142). Finally, the findings of dose response curve suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small beneficial effect and borderline statistical significance. Subgroup analyses for 5 g per day increment in PUFA indicated that the protective effect of PUFA was more evident in women (RR, 0.94; 95% CI, 0.87–1.01; P = 0.095) than in men (RR, 1.00; 95% CI, 0.98–1.02; P = 0.784). Conclusion/Significance Our study indicated that PUFA intake had little or no effect on lung cancer risk. PUFA intake might play an important role in lung cancer prevention in women.

Background Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach. Methodology and Principal Findings In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84–1.01; P = 0.076). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97–1.01; P = 0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100–299 µg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 µg/day). Finally, subgroup analyses of a 100 µg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women. Conclusion/Significance Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men.

Novel hybrid magnetic cross-linked enzyme aggregates of phenylalanine ammonia lyase (HM-PAL-CLEAs) were developed by co-aggregation of enzyme aggregates with magnetite nanoparticles and subsequent crosslinking with glutaraldehyde. The HM-PAL-CLEAs can be easily separated from the reaction mixture by using an external magnetic field. Analysis by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) indicated that PAL-CLEAs were inlayed in nanoparticle aggregates. The HM-PAL-CLEAs revealed a broader limit in optimal pH compared to free enzyme and PAL-CLEAs. Although there is no big difference in Km of enzyme in CLEAs and HM-PAL-CLEAs, Vmax of HM-PAL-CLEAs is about 1.75 times higher than that of CLEAs. Compared with free enzyme and PAL-CLEAs, the HM-PAL-CLEAs also exhibited the highest thermal stability, denaturant stability and storage stability. The HM-PAL-CLEAs retained 30% initial activity even after 11 cycles of reuse, whereas PAL-CLEAs retained 35% of its initial activity only after 7 cycles. These results indicated that hybrid magnetic CLEAs technology might be used as a feasible and efficient solution for improving properties of immobilized enzyme in industrial application.

Background Sequencing of the genome of Propionibacterium acnes produced a catalogue of genes many of which enable this organism to colonise skin and survive exposure to the elements. Despite this platform, there was little understanding of the gene regulation that gives rise to an organism that has a major impact on human health and wellbeing and causes infections beyond the skin. To address this situation, we have undertaken a genome–wide study of gene regulation using a combination of improved differential and global RNA-sequencing and an analytical approach that takes into account the inherent noise within the data. Results We have produced nucleotide-resolution transcriptome maps that identify and differentiate sites of transcription initiation from sites of stable RNA processing and mRNA cleavage. Moreover, analysis of these maps provides strong evidence for ‘pervasive’ transcription and shows that contrary to initial indications it is not biased towards the production of antisense RNAs. In addition, the maps reveal an extensive array of riboswitches, leaderless mRNAs and small non-protein-coding RNAs alongside vegetative promoters and post-transcriptional events, which includes unusual tRNA processing. The identification of such features will inform models of complex gene regulation, as illustrated here for ribonucleotide reductases and a potential quorum-sensing, two-component system. Conclusions The approach described here, which is transferable to any bacterial species, has produced a step increase in whole-cell knowledge of gene regulation in P. acnes. Continued expansion of our maps to include transcription associated with different growth conditions and genetic backgrounds will provide a new platform from which to computationally model the gene expression that determines the physiology of P. acnes and its role in human disease.

Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1)H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS) treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36) were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36) involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC) and indoleamine 2, 3-dioxygenase (IDO) in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1)H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify the comprehensive potential depression-related biomarkers and helpful in further understanding the underlying molecular mechanisms of depression through the disturbance of metabolic pathways.

This study proposed a new strategy for uncovering the active chemical constituents of a traditional Chinese medicines (TCMs) formula, Chaihu-Shu-Gan-San (CSGS). Metabonomics and chemical profile were integrated in combination with the multivariate statistical analysis (MVA) to discover the chemical constituents which contribute to the antidepressant effect of CSGS. Based upon the difference between CSGS and QZ (CSGS without Zhi-Qiao) extracts in the chemical profiles and the regulations of metabolic disturbances induced by CUMS, synephrine, naringin, hesperidin, and neohesperidin were recognized as the active constituents of CSGS from Zhi-qiao responsible for those missing regulations of CSGS when Zhi-Qiao was subtracted from the whole formula. They participated in the regulations of the deviated metabolites2–4,10–14, and22–25, involved in metabolic pathways of ketone bodies synthesis, phenylalanine, tyrosine and tryptophan biosynthesis, valine, aspartate, glutamate metabolism, and glycolysis/gluconeogenesis. Furthermore, the assay of MAO-A activity confirmed the potential antidepressant effect of naringin and its active sites on the MAO-A was inferred by molecular docking study. The integration of metabonomics and chemical profile was proved to be a useful strategy for uncovering what the active chemical constituents in TCM formula are and how they make contributions for the efficacy of the formula.