Search

Background: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown., Methods: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated., Results: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values., Conclusion: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Acupuncture is a method for treating tic disorder. However, there is a lack of sufficient clinical objective basis in regards of its treatment efficacy. Indeed, there are structural abnormalities present in energy metabolism and infrared thermography in children with tic disorder. Therefore, this study proposes a clinical trial scheme to explore the possible mechanism of acupuncture in treating tic disorder., Methods: This randomized controlled trial will recruit a total of 90 children, in which they will be divided into non-intervention group and intervention group. The non-intervention group consists of 30 healthy children while the intervention group consists of 60 children with tic disorder. The intervention group will be randomly allocated into either the treatment group or the control group, with 30 children randomly assigned in each group. Children either received acupuncture treatment and behavioral therapy (treatment group) or sham acupuncture treatment and behavioral therapy (control group), 3 treatment sessions per week for a period of 12 weeks, with a total of 36 treatment sessions. Outcome measures include YGTSS, urinary and fecal metabolomics, infrared thermography of body surface including governor vessel. For the intervention group, these outcome measures will be collected at the baseline and 90th day prior to intervention. Whereas for the non-intervention group, outcome measures (excluding YGTSS) will be collected at the baseline., Discussion: The main outcome will be to observe the changes of the severity of tic condition, the secondary outcome will be to observe the changes of structural characteristic of infrared thermography of body surface/acupoints along the governor vessel and to evaluate the changes of urinary and fecal metabolomics at the end of the treatment, so as to analyze the relationship between them and to provide further knowledge in understanding the possible mechanism of acupuncture in improving the clinical symptoms via regulating and restoring the body metabolomics network, which in future it can develop as a set of clinical guideline (diagnosis, treatment, assessment, prognosis) in treating tic disorder. ChiCTR2300075188(Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 29 August 2023)., (© 2024. The Author(s).)

The mapping of long-wavelength phonons is important to understand and manipulate the thermal transport in multilayered structures, but it remains a long-standing challenge due to the collective behaviors of phonons. In this study, an experimental demonstration of mapping the long-wavelength phonons in an alloyed Al 0.1 Ga 0.9 As/Al 0.9 Ga 0.1 As superlattice system is reported. Multiple strategies to filter out the short- to mid-wavelength phonons are used. The phonon mean-free-path-dependent thermal transport properties directly demonstrate both the suppression effect of the ErAs nanoislands and the contribution of long-wavelength phonons. The contribution from phonons with mean free path longer than 1 μm is clearly demonstrated. A model based on the Boltzmann transport equation is proposed to calculate and describe the thermal transport properties, which depicts a clear physical picture of the transport mechanisms. This method can be extended to map different wavelength phonons and become a universal strategy to explore their thermal transport in various application scenarios.

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Wang et al.)

Background: The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice., Methods: A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy., Results: In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818-1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459-1.000)., Conclusions: The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19., (© 2023. The Author(s).)

Rice husk is one of the most plentiful agriculture by-products in rice producing areas, which harbors a substantial proportion of biological metabolites, however, it has not been well studied. As an attempt to utilize it as a productive manner, phytochemical investigation on rice husk has performed and led to the isolation of three undescribed (1, 2, and 7), along with twelve known components (3-6, and 8-15). Those chemical structures were elucidated based on massive spectroscopic methods. Among them, compounds 4, 6-8, and 10-13 have been shown to act as α-glucosidase inhibitors. Notably, the most active compounds, 10/11, demonstrated comparable α-glucosidase inhibitory effect (IC 50  = 1.83 ± 0.11 μg/mL) to that of 1-deoxynojirimycin (IC 50  = 1.02 ± 0.16 μg/mL). For the molecular docking simulation studies, compounds 10/11 showed relative binding interactions with α-glucosidase enzyme (PDB ID: 3A4A) that similar to those reference inhibitors. Additionally, the crude extract of O. sativa demonstrated better α-glucosidase inhibitory effect to that of isolated components, with the IC 50 value at 1.25 ± 0.07 μg/mL., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian Lin Li reports financial support was provided by Nantong Science and Technology Commission. Jian Lin Li reports a relationship with Nantong Science and Technology Commission that includes: funding grants. Jian Lin Li has patent Antifungal diterpenoid form the husks of rice pending to Jian Lin Li., (Copyright © 2023. Published by Elsevier B.V.)

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts., (© 2023. People´s Military Medical Press.)

Objective: To understand the distribution characteristics of age of Alzheimer's disease (AD) onset and influencing factors. Methods: Based on the follow-up data of Alzheimer's Disease Neuroimaging Initiative from 2005 to 2022, participants with normal cognition (CN) or mild cognitive impairment (MCI) at baseline survey, and those with progression to AD during follow-up period were selected as study subjects. Univariate analysis and multiple linear regression analysis were performed to explore the associations of gender, race, number of ApoE ε 4 genes carried, family history, years of education and marital status with the age of AD onset. Results: A total of 405 participants, with an average age of (74.0±6.9) years at baseline survey, progressed to AD during follow up period. The age of AD onset was (76.6±7.5) years, and age of onset in men was about 1.9 years later than women. Multiple linear regression analysis showed that for each increase in ApoE ε 4 gene number, the age of AD onset was about 0.344 years earlier. The age of AD onset was 4.007 years earlier for those with MCI at baseline survey compared with those with CN. Years of education were not significantly associated with the age of onset of AD ( P >0.05). Conclusion: Those who carry ApoE ε 4 gene, and have MCI at baseline survey might have earlier age of AD onset.

Background: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT04288102)., Methods: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 10 7  cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs)., Findings: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04-0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00-20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups., Interpretation: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period., Funding: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6)., Competing Interests: Declaration of interests HF, WQY, YZ and RDB are current employees of Wuhan Optics Valley Zhongyuan Pharmaceutical Co.,Ltd. TYD and LLZ are current employees of Wuhan Optics Valley Vcanbio Cell & Gene Technology Co., Ltd. All authors declare no other conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the mechanism of VPS26 effect on osteogenesis and adipogenesis differentiation of rat bone marrow mesenchymal stem cells (BMSC) in high fat environment, and to explore the effect of VPS26 on implants osseointegration of high fat rats and ectopic osteogenesis in nude mice. Methods: BMSC were cultured under normal osteogenic induction (osteogenic group) and high-fat osteogenic induction (high-fat group).High-fat group was transfected with VPS26 enhancer and inhibitor, and the expression levels of osteogenesis related genes and adipogenesis related genes were examined. Osteogenesis and adipogenesis of BMSC were detected by alkaline phosphatase (ALP) staining and oil red O staining after 7 and 14 days of induction.In osteogenic group,the binding of VPS26 to β-catenin was detected by immunofluorescence staining and immunoprecipitation, and dual luciferase reporter assay (TOP Flash) was used to analyze the TOP/FOP ratio. Eighteen male 12-week hyperlipidemic Wista rats (160-200 g) were implanted with implants, and six in each group were injected with VPS26 overexpression lentivirus (LV-VPS26 group), negative control lentivirus (LV-nc group) and saline (blank control group).Micro-CT analysis , HE and oil red O staining were used to evaluate the osseointegration of the implants and lipid droplets formation of the femur samples. Twenty female 6-week nude mice (30-40 g) were divided into five groups and subcutaneously implanted with osteogenic BMSC non-transfected and transfected LV-VPS26, LV-nc, shVPS26, and shscr lentivirus on the back. Samples were used to observe ectopic osteogenesis. Results: The mRNA expression levels of ALP in the high-fat group BMSC after overexpression of VPS26 (1.56±0.09) were significantly higher than those of the negative control (1.01±0.03) ( t =10.09, P <0.001), while those of peroxisome proliferator-activated receptor-γ (PPAR-γ) ( t =6.44, P <0.001) and fatty acid-binding protein4 (FABP4) ( t =10.01, P <0.001) were lower than those of the negative control. Western blotting results showed that compared with the negative control, protein expression of ALP and Runt-related transcription gene 2 was enhanced in the high-fat group BMSC after overexpression of VPS26 while PPAR-γ and FABP4 were inhibited. ALP activity of BMSC in the high-fat group was stronger after overexpression of VPS26, and the formation of lipid droplets was weaker than that in negative control. The results of immunofluorescence, immunoprecipitation and dual luciferase reporter assays showed co-localization and interaction of VPS26 with β-catenin and a significant 43.10% increase in the TOP/FOP ratio ( t =-3.17, P =0.034). VPS26 overexpression enhanced osseointegration and decreased the number of lipid droplets in high-fat rat and enhanced ectopic osteogenesis of nude mice. Conclusions: VPS26 activated osteogenesis differentiation and inhibited adipogenic differentiation of BMSCs through Wnt/β-catenin pathway, promoting osseointegration of high-fat rat implants and ectopic osteogenesis of nude mice.

Elongation factor Tu GTP binding domain protein 2 (Eftud2) is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection. Microglia are the resident innate immune cells and the key players of immune response in the central nervous system. However, the role of Eftud2 in microglia has not been reported. In this study, we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer's disease. Next, we generated an inducible microglia-specific Eftud2 conditional knockout mouse line (CX3CR1-CreER; Eftud2 f/f cKO) via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia. Furthermore, we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway. Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway., Competing Interests: None

In recent years, sexual assault cases have been on the rise, seriously infringing the legitimate rights and interests of women and children, causing widespread concern in society. DNA evidence has become the key evidence to prove the facts in sexual assault cases, but lack of DNA evidence or only DNA evidence in some sexual assault cases leads to unclear facts and insufficient evidence. With the emergence of high-throughput sequencing technology and the development of bioinformatics and artificial intelligence, new progress has been made in the study of human microbiome. Researchers have begun to use human microbiome for difficult sexual assault cases indentification. This paper reviews the characteristics of human microbiome, and its application value in the inferences of the body fluid stain origin, the sexual assault method, the crime time, etc. In addition, the challenges faced by the application of the human microbiome in practical case handling, the solutions and future development potential are analyzed and prospected.

Objective: To explore the developmental trajectory of multimorbidity and its impact on new-onset disability to identify homogeneous groups with similar multimorbidity developmental courses and to provide evidence for interventions for disability risk among middle-aged and older adults in China. Methods: Data was retrospectively collected from China Health and Retirement Longitudinal Study with four consecutive surveys (2011-2018). Group-based trajectory modeling was used to fit multimorbidity developmental trajectories, and the impact of multimorbidity trajectories on new-onset disability was analyzed using the time-dependent Cox regression model. Results: A total of 8 580 participants were included in current analysis, and four multimorbidity trajectories were identified: no multimorbidity ( n =2 136, 24.90%), newly-developing ( n =3 758, 43.80%), moderate-developing ( n =2 270, 26.45%) and severe-developing ( n =416, 4.85%). Participants who belong to moderate-developing and severe-developing tended to be female, single, overweight or obese, live in rural areas, have poorer self-rated health and high levels of annual per capita household expenditure, and developed a new-onset disability. After adjusting for demographic and behavioral covariates, compared to the newly-developing, the severe-developing( HR =3.132, 95% CI :1.884-5.207) had the highest risk of disability, followed by the moderate- developing ( HR =1.400, 95% CI :1.026-1.909) and the risk for the no multimorbidity ( HR =0.631, 95% CI :0.424-0.938) was the lowest. Conclusions: There was great heterogeneity in the developmental trajectory of multimorbidity among middle-aged and older adults in China. Data showed that the risk of disability in the developmental trajectory of multimorbidity increases with increasing levels. We think that the elevating developmental trajectory of multimorbidity is a risk factor for developing disability.

Oreocharisqianyuensis , a new species of Gesneriaceae from Southwest, China, is described and illustrated based on morphological comparisons and molecular phylogenetic analyses. Phylotranscriptomic analyses of the new species in the context of a comprehensive phylogeny with dense sampling of 88% (111/126) of all species of the genus indicated that the new species was most closely-related to O.fargesii . The new species is morphologically similar to O.fargesii and O.nanchuanica in the shape, color and structure of flowers and the number of stamens, but differs in the leaf blade shape, margin and the indumentum characters of the inflorescence. Its morphological relationship with similar species is discussed, the detailed descriptions, colour photographs, distribution, as well as the IUCN threatened status based on the IUCN Red List Categories and Criteria are also provided., (Jia-Wen Yang, Xin-Mei Qin, Jian Xu, Cong-Rui Li, Qi-Fei Ren, Mao-Qin Yuan, Qiang Zhang, Si-Rong Yi, Lei Cai.)

Objective: To understand the transition rules of cognitive frailty and its influencing factors in the elderly in China and provide evidence for the early intervention of cognitive frailty. Methods: Data were retrospectively collected from China Health and Retirement Longitudinal Study with 3 round consecutive survey (2011, 2013, 2015) and the state of the subjects were classified into four categories: robust-normal cognitive, cognitive impairment, physical frailty, and cognitive frailty. A multi-state Markov model was established to explore the transition rules of cognitive frailty and its influencing factors. Results: A total of 3 470 older adults were included, and 350 (10.09%) had cognitive frailty at baseline. After two years, the probability of cognitive frailty in the cognitive impairment population was higher than that in people with physical frailty (31.6% vs. 7.6%). Persons with cognitive frailty were more likely to become physical frailty (29.7% vs. 15.6%). Being women ( HR =1.599, 95% CI : 1.058-2.417), comorbidity ( HR =3.035, 95% CI : 1.090-8.450), and depression ( HR =1.678, 95% CI : 1.153-2.441) were the risk factors associated with cognitive frailty in the elderly, while being educated ( HR =2.367, 95% CI : 1.567-3.575) was a protective factor for the transition of cognitive frailty to physical frailty. Conclusions: The prevalence of cognitive frailty is relatively high in the elderly in China. Those with cognitive impairment have a higher probability of cognitive frailty. Gender, education level, comorbidity, and depression are the main influencing factors for the occurrence and transition of cognitive frailty.

Objective: To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Methods: Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)&#95;immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter ( α ). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of ( t, t+ Δ t ). The starting point t was selected at the 30 th , 42 nd , and 54 th month, and the Δ t was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Results: Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI ( P <0.001). The risk of MCI decreased by 32.3% ( HR =0.677, 95% CI : 0.541-0.846) and 10.8% ( HR =0.892, 95% CI : 0.865-0.919) for each one-point increase of MMSE and RAVLT&#95;immediate longitudinal scores. The risk of MCI increased by 53.2% ( HR =1.532, 95% CI : 1.393-1.686), 36.2% ( HR =1.362, 95% CI : 1.268-1.462), 23.2% ( HR =1.232, 95% CI : 1.181-1.285), and 85.1% ( HR =1.851, 95% CI :1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT&#95;immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. Conclusions: The RAVLT&#95;immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT&#95;immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.

Chemotherapy combined with surgery is effective for patients with breast cancer (BC). However, chemoresistance restricts the effectiveness of BC treatment. Immune microenvironmental changes are of pivotal importance for chemotherapy responses. Thus, we sought to construct and validate an immune prognostic model based on chemosensitivity status in BC. Here, immune-related and chemosensitivity-related genes were obtained from GSE25055. Then, univariate analysis was employed to identify prognostic-related gene pairs from the intersection of the two parts of the genes, and modified least absolute shrinkage and selection operator (LASSO) analysis was performed to build a prognostic model. Furthermore, we investigated the efficiency of this model from various perspectives, and further validation was performed using the Cancer Genome Atlas (TCGA) cohorts. We identified seven immune and chemosensitivity-related gene pairs and incorporated them into the Cox regression model. After multilevel validation, the risk model was found to be closely related to the survival rate, various clinical characteristics, tumor mutation burden (TMB) score, immune checkpoints, and response to chemotherapeutic drugs. In addition, the model was verified to exhibit predictive capacity as an independent factor over other candidate clinical features. Notably, the constructed nomogram was more accurate than any single factor. Altogether, the risk score model and the nomogram have potential predictive value and may have important practical implications., 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 © 2021 Deng, Hu, Dai, Yuan, Hu and Cheng.)

Objective: To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy., Methods: Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics., Results: Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment ( P <0.05), and the DQ score of fine motor in the rehabilitation group was increased after treatment ( P <0.05). Compared with the normal group, the serum L-glutamate, L-ornithine, L-tyrosine, L-methionine and L-arginine in the cerebral palsy group were down-regulated, and L-histidine, L-citrulline, 5-hydroxylysine and L-glutamine were up-regulated before treatment. The functional pathways mapped by different metabolites between the cerebral palsy group and the normal group included arginine biosynthesis, arginine and proline metabolism, etc. Compared with the cerebral palsy group, the serum L-histidine was decreased, and L-citrulline showed decreasing trend in the acupuncture and rehabilitation group after treatment., Conclusion: Acupuncture combined with rehabilitation training could improve cognitive function in children with cerebral palsy, and the effect may be related to the down-regulation of L-histidine and L-citrulline metabolism.

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Deng et al.)

Background: Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME)., Method and Result: We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through "xCell" algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes ( CXCL9 , VSIG4 , ALOX5AP , TGFBI , UBD , and CXCL11 ). And DC-related risk stratify model had been well established and validated., Conclusion: High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Shi-yi Liu et al.)

Abstract: Objective To develop an SNP Panel for East Asian population, which has a high individual identification rate and the capability of ancestry analysis. Methods The 55 SNP Panel by Professor KIDD of Yale University and the 128 SNP Panel by Professor SELDIN of Davis School of California University, 170 SNP Panel in total was used as the basis and its test data in the East Asian population was collected. The genetic parameters of SNP loci were calculated and combined with the results of heatmap analysis to screen SNP loci suitable for East Asian population. Some Tibetan and Han samples were tested. The possibility of using the SNP loci in ancestry inference was analyzed by means of STRUCTURE analysis, principal component analysis and heatmap analysis. Results A Panel with 45 SNPs （45 SNP Panel） was screened out, and the average genetic parameters of each SNP were better than 170 SNP Panel, with the same ancestry analysis and inference ability. Conclusion In terms of ancestry inference information, the 45 SNP Panel can completely replace the 170 SNP Panel and achieve the same ancestry analysis and inference ability. In genetic parameters, 45 SNP Panel is better than 170 SNP Panel in the East Asian population, which shows its important potential forensic application value., 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 Forensic Medicine.)

Luteoloside (Lute), a bioactive natural ingredient, widely exists in nature and possesses hepatoprotective and hepatocyte proliferation-promoting properties. This study aimed to investigate whether Lute could counteract non-alcoholic fatty liver disease (NAFLD)-caused hepatocyte damage via its stimulation of hepatocyte regeneration efficacy and to explore the involved mechanism. LO2 cells and primary hepatocytes were used to examine the hepatocyte proliferation effects of Lute under physiological conditions and in the palmitic acid (PA)- induced in vitro model of NAFLD. STAT3 and cell cycle-related proteins (cyclin D1, c-myc and p21) were evaluated by Western blot. Under physiological conditions, LO2 cells and primary hepatocytes treated with various concentration of Lute for 12 and 24 h showed increased hepatocyte proliferation, especially with 20 μM treatment for 24 h. More notably, under the model conditions, co-incubation with 20 μM of Lute also markedly reversed PA-induced inhibition of cell proliferation and viability in primary hepatocytes. Mechanistically, Lute could activate STAT3 and subsequently increase cyclin D1 and cmyc expression, which positively regulates cell cycle progression, and decrease expression of p21, an inhibitor of cell cycle progression. Furthermore, Luteinduced hepatocyte proliferation-promoting efficacy was abolished by STAT3 inhibitor stattic. Collectively, Lute can alleviate PA-induced hepatocyte damage via activating STAT3-mediated hepatocyte regeneration.

The effects of adverse childhood experiences on adult health has aroused increasing concern in the world in recent years, but limited studies have been conducted in China. This study synthesized the measurement of adverse childhood experiences, the association between adverse childhood experiences and the prevalence common chronic diseases in adulthood and possible mechanisms. It was found that though measurement range of adverse childhood experiences might be different among studies, current used measurement scales basically met the requirement of disease prevention. Most categories of adverse childhood experiences were positively related to risk of common chronic diseases, and the relationship was influenced by social economic status, sex and age. However, people with exposure to famine in childhood had lower prevalence of hypertension compared with those without the exposure. The possible mechanisms might be that the occurrence of adverse childhood experiences might damage physiological functions or increase the adoption of poor healthy behaviors and lifestyles, and finally increased the risk of chronic diseases directly or indirectly. While premature death due to adverse childhood experiences might reverse the association because of nonrandom selection. It is necessary for us to select appropriate indexes of adverse childhood experiences and conduct more studies to prove the association between adverse childhood experiences and prevalence of common chronic diseases in adulthood and explore the related mechanism for the better prevention of chronic diseases in China.

Endophytic fungi produce many novel bioactive metabolites that are directly used as drugs or that function as the precursor structures of other chemicals. The metabolic shaping of endophytes on grape cells was reported previously. However, there are no reports on the interactions and metabolic impact of endophyte symbiosis on in vitro vine leaves, which may be examined under well-controlled conditions that are more representative of the natural situation of endophytes within grapevines. The present study used an in vitro leaf method to establish endophyte symbiosis of grapevines and analyze the effects on the metabolic profiles of grape leaves from two different cultivars, 'Rose honey' (RH) and 'Cabernet sauvignon' (CS). The effects of endophytic fungi on the metabolic profiles of grape leaves exhibited host selectivity and fungal strain specificity. Most of the endophytic fungal strains introduced novel metabolites into the two varieties of grape leaves according to the contents of the detected metabolites and composition of metabolites. Strains RH49 and MDR36, with high or moderate symbiosis rates, triggered an increased response in terms of the detected metabolites, and the strains MDR1 and MDR33 suppressed the detected metabolites in CS and RH leaves despite having strong or moderate symbiosis ability. However, the strain RH12 significantly induced the production of novel metabolites in RH leaves due to its high symbiosis ability and suppression of metabolites in CS leaves., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Cerebral palsy is the most common motor disability of childhood. Spastic cerebral palsy accounts for 60% to 70% of cases. Research has shown that acupuncture can improve the quality of life of children with cerebral palsy, but the mechanism of action remains unclear. This study aims to determine the effectiveness of acupuncture for treatment of children with spastic cerebral palsy and to assess the value of multimodal magnetic resonance imaging (MRI) and ambulatory electroencephalogram (EEG) for evaluation of treatment effect., Methods and Analysis: This randomized controlled trial will enroll a total of 72 children with CP from 2 hospitals-Jiangsu Province Hospital of Chinese Medicine and Nanjing State Hospital of Pediatric-with 36 participants from each hospital. Patients will be randomly assigned (1:1 ratio) to receive "Tonifying Kidney and Invigorating Brain" acupuncture treatment plus standardized physical rehabilitation treatment (treatment group) or only standardized physical rehabilitation (control group). All participants will receive 3 treatment sessions per week for 3 consecutive months; they will then be followed up for another 3 months. The primary outcome measures will include multimodal magnetic resonance imaging (MRI), ambulatory electroencephalogram (EEG), and Gesell Developmental Diagnostic Schedules. The secondary outcome measures will include Gross Motor Function Classification System (GMFCS), Gross Motor Function Measure (GMFM), Functional Independence Measure (WeeFIM), and Modified Ashworth Scale score. Outcome measures (including primary and secondary outcome measures) were collected at the baseline, 3 months and 6 months prior to the intervention.Ethics and dissemination PATIENTS CONSENT:: Obtained., Ethics Approval: The central independent ethics committee of Jiangsu Province Hospital of Traditional Chinese Medicine approved the protocol (2017NL-115-02)., Safety Considerations: Routine blood tests and liver and kidney function tests will be conducted to exclude patients with severe heart, liver, or kidney diseases. The same examinations will be performed again at the end of the study to detect any possible side effects. Possible acupuncture-related adverse events (e.g., fainting, needle stick injury, local infection, subcutaneous hematoma, and low-grade fever) will be documented. Serious adverse events will be reported to the principal investigator immediately. All unexpected and unintended responses, even those not necessarily related to the acupuncture intervention, will be documented as adverse events., Case Dropout Management: Participants have a right to withdraw from the study at any time if they feel uncomfortable upon receiving the treatments or being diagnosed with serious complications or diseases. They will then be referred to the preferred department for further treatment and management. If cases of dropout, the researcher need to contact the participant to reason the problem out, collect and record all the necessary assessments on the last visit as well as the date of last visit. All data available until the date of withdrawal will be stored for further statistical analysis., Discussion: This research is being conducted to assess the value of acupuncture as an intervention for rehabilitation of children with spastic cerebral palsy and also to evaluate the usefulness of multimodal MRI and ambulatory EEG for identifying changes in brain function., Trial Registration: This trial is registered with Chinese Clinical Trials Register, ChiCTR 1900024546 (registered 15 July 2019; retrospective registration, http://www.chictr.org.cn/showproj.aspx?proj=35763).

Endometriosis is a common gynecological disease characterized by the presence and growth of endometrial tissue outside the uterus, including the pelvis and abdominal cavity. This condition causes various clinical symptoms, such as non-menstrual pelvic pain, dysmenorrhea and infertility, seriously affecting the health and quality of life of women. To date, the specific mechanism and the key molecules of endometriosis remain uncertain. The purpose of the present study was to elucidate the mechanisms involved in the development and persistence of the disease. A number of mRNA expression profile datasets (namely GSE11691, GSE23339, GSE25628 and GSE78851) were downloaded from the Gene Expression Omnibus (GEO) database. These gene expression profiles were normalized, and the differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis. A total of 103 DEGs were screened upon excluding the genes that exhibited inconsistency of expression (P<0.05). Furthermore, the Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and construction of protein-protein interaction networks of DEGs were performed using online software. The results revealed that the DEGs were closely associated with cell migration, adherens junction and hypoxia-inducible factor signaling. In addition, immunohistochemical assay results were found to be consistent with the bioinformatics results. The present study may help us understand underlying molecular mechanisms and the development of endometriosis, which has a great clinical significance for early diagnosis of the disease., (Copyright: © Dai et al.)

Post inflammatory irritable bowel syndrome (PI-IBS), a subset of IBS, is characterized by symptoms of visceral pain, bloating, and changed bowel habits that occur post initial episode of intestinal infection. Gut microbial dysbiosis or inflammation plays a key role in the pathogenesis of abdominal hypersensitivity of PI-IBS. Electroacupuncture (EA) stimulation results in an alleviated PI-IBS-associated symptom. This study investigated the effect of EA on IL-18 and gut microbial dysbiosis in one visceral hypersensitive rat models with PI-IBS. A trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity rat model was developed. EA stimulation was applied to the ST25 and ST36 acupoints. Animals were assessed using abdominal withdrawal reflex (AWR) scores to determine the development of colonic visceral hypersensitivity. The 16S rRNA was used to correlate microbial diversity. IL-18 expression in colon was quantified by quantitative real-time PCR and western blotting. We identified that model rats had an increased visceral hypersensitivity to colorectal distention at different distention pressures compared with the normal group. Sensitivity to colorectal distention decreased after EA stimulation. The composition of the fecal microbiota was different between groups. Specifically, in the model group Empedobacter, Psychrobacter, Enterococcus, Butyricimonas, Vampirovibrio, Kurthia, Intestinimonas, Neisseria, Falsiporphyromonas, Bilophila, Fusobacterium, Alistipes, Veillonella, Flavonifractor, Clostridium XlVa were more abundant affected genera, whereas Lactobacillus was enriched in normal rats. EA stimulation was correlated with significant decrease in the phyla of Fusobacteria . The mRNA and protein levels of IL-18 were higher in the model group. Meanwhile, EA stimulation attenuated this response. In a word, our findings suggest that PI-IBS is associated with significant increase in IL-18 levels as well as an alteration in microbiome diversity. These changes can be reversed with EA treatment. EA stimulation has a positive effect in alleviating symptoms of visceral hypersensitivity and protecting the gastrointestinal tract.

Professor SHENG Can-ruo is a well-known national veteran doctor with over 70 years of clinical experience. He has unique academic thoughts and clinical experience for common diseases and some difficult and complicated diseases. This paper mainly introduces professor SHENG 's syndrome-differentiation thought and experience of acupoint selection for hot flashes. It is emphasized that common hot flashes, such as hot flashes and night sweats, are different between yin and yang . While regulating yin and yang , more attention should be paid to ying - wei harmony, which is not only suitable for women's perimenopausal syndrome, but also for a series of clinical diseases caused by refractory drugs such as endocrine therapy after breast cancer surgery. At the same time of acupoint selection based on syndrome differentiation, a more rational prescriptions should be made according to the duration of the disease and the experience acupoints to improve the clinical efficacy.

miRNAs are small non-coding RNAs modulating gene expression, and variants in miRNA genes are involved in the pathogenesis of ischemic stroke (IS). However, the effect of miR-34a polymorphisms on IS susceptibility has rarely been reported. In the present study, we investigated the association between rs12128240, rs2666433, and rs6577555 of the miR-34a gene and IS susceptibility. Snapshot assay was used to detect miR-34a polymorphisms in 548 IS patients and 560 controls. Relative expression of miR-34a was measured by quantitative real-time PCR. We found that rs2666433 was associated with a significantly increased risk of IS (AA vs. GG: OR = 1.61, 95% CI = 1.05-2.52, P = 0.031; AA vs. GG+GA: OR = 1.58, 95% CI = 1.05-2.45, P = 0.026). For the IS subtypes, rs2666433 was associated with large artery atherosclerosis (AA vs. GG: OR = 2.09, 95% CI = 1.16-3.51, P = 0.007; AA vs. GG+GA: OR = 2.02, 95% CI = 1.15-3.33, P = 0.007; A vs. G: OR = 1.36, 95% CI = 1.07-1.81, P = 0.021). Additionally, the level of miR-34a was significantly up-regulated in IS patients compared to the controls ( P < 0.001), and patients with rs2666433 AA genotype had a higher level of miR-34a than those with GG+GA genotypes ( P < 0.001). Furthermore, increased level of homocysteine was observed in IS patients compared to the controls ( P < 0.001), especially in patients carrying the rs2666433AA genotype compared to those carrying the rs2666433 GG+GA genotypes ( P < 0.001). However, no significant association between rs12128240 or rs6577555 and IS was found. Collectively, our study found the association between miR-34a polymorphisms and the risk of IS among the Chinese population. The results may provide an explanation for etiology of IS and a potential biomarker or therapeutic target for IS. HIGHLIGHTS-MiR-34a rs2666433 polymorphism was associated with an increased risk of ischemic stroke.-The level of miR-34a was significantly up-regulated in ischemic stroke patients compared with controls, and patients with rs2666433 AA genotype had a higher level miR-34a than those with GG+GA genotypes.-Furthermore, increased level of homocysteine was showed in IS patients compared to controls, and in patients carrying the rs2666433AA compared to those carrying the rs2666433 GG+GA.

Objective: To explore the cognitive functions of the elderly aged 60 years and above in Xiamen, and whether TV watching time would affect those functions. Methods: We conducted a cross-sectional study on 3 230 registered individuals aged 60 years and above in Xiamen from July to October in 2016 with a multi-stage random sampling method. Montreal Cognitive Assessment (MoCA) was used to measure cognitive functions and ordinal logistic regression was used to quantify their associations with TV watching time. Results: A total of 2 944 respondents were included in this study. The overall age of them was (70.14±7.81) years. 51.49% ( n= 1 516) of all participants were men. Overall, the mean scores of MoCA in general and each subdomain cognitive function were 18.65±6.43 (general), 5.43±1.17 (orientation), 2.33±1.95 (memory), 1.80±1.52 (visuospatial), 1.66±1.20 (executive), 4.54±1.71 (attention), and 4.09±1.64 (language). Compared to those who watched TV no more than 2 hours per day, the elderly who did not watch TV had a worse performance in general, orientation, memory, visuospatial, executive, attention, language function, with OR (95 %CI ) values about 0.50 (0.35-0.71), 0.52 (0.37-0.73), 0.68 (0.48-0.96), 0.67 (0.47-0.96), 0.48 (0.34-0.67), 0.56 (0.41-0.77) and 0.45 (0.33-0.62), respectively. As to respondents who watched TV more than 2 hours but no more than 4 hours per day, they had a better performance in general, executive, attention, language, and orientation function with respective OR (95 %CI ) values about 1.24 (1.05-1.47), 1.20 (1.02-1.41), 1.41 (1.19-1.67), 1.51 (1.28-1.77) and 1.33 (1.08-1.64). Conclusion: The elderly aged 60 years and above in Xiamen City with TV watching time between 2 and 4 hours per day had a good performance in cognitive functions compared to those with more or less TV watching time.

Since endophytes can affect metabolism of host plants, they are expected to be used to improve crop quality, especially for crops with organoleptic sensitive products such as wine grape. However, details of metabolic interactions between endophytes and host plants were less understood. In this work, we used high pressure liquid chromatography (HPLC) to analyze the metabolites of fruit flesh cells of grape treated with dual culture of different endophytic fungal strains (EFS). We observed that the dual-culture with different fungal strains show different metabolites composition in grape cells. In response to different EFS, quantities of detected metabolites in grape cells varied from 6 to 17 in this assay, and 1 to 11 novel metabolites were introduced into metabolome of grape cells. Dual-culture with fungal strains CS2, RH16 and RH5 introduced the highest quantities (10 or 11) of novel metabolites in grape cells. More importantly, the modification of metabolic profiles in grape cells via fungal endophytes appeared to be fungal strain/genus-specificity. Overall, this work revealed that introduction of specific metabolites in host plants may be one consequence during the process of endophytes-host metabolic interactions, which raise the possibility to shape grape qualities and characteristics using tool of fungal endophytes.

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC-MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p -coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.

Objective: To establish a dynamic spatiotemporal spread modes of influenza A (H7N9) virus by using discrete geographic information and explore the spatiotemporal transmission of the virus. Methods: The gene sequences of H7N9 virus isolated from human in China, which were available from Global Initiative on Sharing Avian Influenza Data (GISAID), were used in alignment by using software BioEdit 7.0. Spatiotemporal spread model of H7N9 virus was established in a Bayesian statistical framework by using software BEAST 1.8.2. The symmetric substitution model and Bayesian stochastic search variable selection (BSSVS) were used to infer and verify the historical transmission route of H7N9 virus. Finally the spatiotemporal transmission route was presented by Google Earth software. Results: The transmission of avian influenza A (H7N9) virus originated in Shanghai and Hangzhou, and can be dated back to October 2012. In March and April 2013, it began to spread to the neighboring provinces. The transmission speed up in August and September and affected more than ten geographic positions within 3 months. Conclusion: Based on gene sequences and spatial geographic information, the transmission route of H7N9 virus was traced, which would support the avian influenza prevention and control as well as avian influenza virus tracing.

Endophytes proved to exert multiple effects on host plants, including growth promotion, stress resistance. However, whether endophytes have a role in metabolites shaping of grape has not been fully understood. Eight endophytic fungal strains which originally isolated from grapevines were re-inoculated to field-grown grapevines in this study, and their effects on both leaves and berries of grapevines at maturity stage were assessed, with special focused on secondary metabolites and antioxidant activities. High-density inoculation of all these endophytic fungal strains modified the physio-chemical status of grapevine to different degrees. Fungal inoculations promoted the content of reducing sugar (RS), total flavonoids (TF), total phenols (TPh), trans-resveratrol (Res) and activities of phenylalanine ammonia-lyase (PAL), in both leaves and berries of grapevine. Inoculation of endophytic fungal strains, CXB-11 (Nigrospora sp.) and CXC-13 (Fusarium sp.) conferred greater promotion effects in grape metabolic re-shaping, compared to other used fungal strains. Additionally, inoculation of different strains of fungal endophytes led to establish different metabolites patterns of wine grape. The work implies the possibility of using endophytic fungi as fine-tuning regulator to shape the quality and character of wine grape., Competing Interests: The authors have declared that no competing interests exist.

Fresh cut Chinese water-chestnut is a popular ready-to-eat fresh-cut fruit in China. However, it is prone to etiolation and the chemicals responsible for this process are not known yet. To address this problem, we extracted phytochemicals from etiolated Chinese water-chestnut and separated them using MPLC and column chromatography. Four compounds were obtained and their structures were determined by interpretation of UV, TLC, HPLC and NMR spectral data and by comparison with reported data. We identified these compounds as eriodictyol, naringenin, sucrose and ethyl D-glucoside. Among those, eriodictyol and naringenin were both isolated for the first time in fresh-cut Chinese water-chestnut and are responsible for the yellowing of this fruit cutting., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma., Methods: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan-Meier method and then compared using the log-rank test., Results: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001)., Conclusions: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response of palliative chemotherapy and the long-term survival outcomes.

The accidental release of radioactive materials from nuclear power plant leads to radioactive pollution. We apply an augmented ensemble Kalman filter (EnKF) with a chemical transport model to jointly estimate the emissions of Perfluoromethylcyclohexane (PMCH), a tracer substitute for radionuclides, from a point source during the European Tracer Experiment, and to improve the forecast of its dispersion downwind. We perturb wind fields to account for meteorological uncertainties. We expand the state vector of PMCH concentrations through continuously adding an a priori emission rate for each succeeding assimilation cycle. We adopt a time-correlated red noise to simulate the temporal emission fluctuation. The improved EnKF system rapidly updates (and reduces) the excessively large initial first-guess emissions, thereby significantly improves subsequent forecasts (r = 0.83, p < 0.001). It retrieves 94% of the total PMCH released and substantially reduces transport error (>80% average reduction of the normalized mean square error)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases., (Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.)

To reduce the toxic effect on normal cells and improve the treatment effects of docetaxel, a novel transferrin modified docetaxel-loaded long circulating liposome for ovarian tumor was established for the first time. The transferrin-modified long-circulating liposomes loaded with docetaxel (TF-LP-DOC) were prepared by the post-insertion method and exhibited excellent characteristics in terms of particle size, encapsulation efficiency and stability. We investigated the targeting efficiencies of liposomes by the cellular uptake in vitro and biodistribution in vivo, and identified the therapeutic effects using cytotoxicity experiment (in vitro)and tumor growth inhibition (in vivo) on ovarian cancer. The in vitro and in vivo results showed that TF-LP-DOC were successfully established and presented an enhanced targeting ability. With decreased side effect and improved anti-tumor efficacy of chemotherapeutic drugs, TF-LP-DOC proved itself to be a very promising tumor targeted drug delivery system., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective/hypothesis: To estimate the aerodynamic multiparameters for patients with muscular tension dysphonia (MTD) and evaluate voice aerodynamic analysis for assisting the diagnosis of this disorder., Study Design: A prospective study., Methods: Voice aerodynamic parameters, including subglottal pressure (SGP) level, glottal resistance (GR), mean airflow rate (MFR), and maximum phonation time (MPT), for 26 MTD patients and 27 normal adults were analyzed using receiver operating characteristics (ROC) analysis and multivariate logistic regression., Results: For male samples, MTD patients had higher SGP (P=0.001), higher GR (P=0.012), lower MFR (P=0.042), and shorter MPT (P=0.027), whereas for female samples, the difference between cases and controls was statistically significant only in SGP (P<0.001) and MPT (P<0.001). ROC analysis showed that the threshold of 8.175 cm H(2)O for SGP achieved a good classification for MTD, with an adequate sensitivity (76.9%) and the perfect specificity (100%). Finally, multivariate logistic regression established a credible model (with SGP and MPT as the predictors) for classifying MTD, with a 92.5% percentage correct., Conclusions: This analysis indicates that aerodynamics evaluation could help the diagnosis of MTD patients, jointly with medical history scrutiny, physical examination, fibrolaryngoscopy, and/or videoendostroboscopy., (Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.)

Folate derivatives are crucial growth factors for Ketogulonigenium vulgare which is used in mixed culture with Bacillus megaterium for the industrial production of 2-keto-L-gulonic acid (2-KGA), the precursor of L-ascorbic acid (L-AA) or vitamin C (Vc). To improve the growth and 2-KGA production, five genes involved in folate biosynthesis identified in a folate gene cluster from Lactococcus lactis MG1363, including folB, folKE, folP, folQ and folC, were over-expressed in K. vulgare. Intracellular folate concentration in the recombinant strain harboring folate biosynthesis genes cluster under the control of P(sdh) (sorbose dehydrogenase gene sdh promoter from K. vulgare) was 8 times higher than that of the wildtype K. vulgare DSM 4025 (P<0.001). In shake flask studies, the cell density and 2-KGA production of the recombinant K. vulgare Rif (pMCS2PsdhfolBC) were increased by 18% (P<0.001) and 14% (P<0.001), respectively, under a relatively stable pH 7 condition. In fermentor studies, enhancements around 25% cell density (P<0.001) and approximately 35% 2-KGA productivity (P<0.001) were observed in comparison with the controls without over-expressing the folate biosynthesis genes. This was the first successful study of metabolic engineering on K. vulgare for enhanced 2-KGA production., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Polyhydroxyalkanoate synthase gene phaC(ah) in Aeromonas hydrophila strain 4AK4 was deleted and its function was replaced by phaC1(ps) cloned from Pseudomonas stutzeri strain 1317 which favors 3-hydroxyhexanoate (3HHx) and longer chain length monomers. Genes fadD and fadL encoding Escherichia coli acyl-CoA synthase and Pseudomonas putida KT2442 fatty acid transport protein, respectively, were introduced into the recombinant with new phaC1(ps). Accumulation of a series of novel medium-chain-length polyhydroxyalkanoates (mcl-PHA) consisting of 80-94 mol% 3HHx were observed. The recombinant accumulated 54% poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) in cell dry weight consisting of 94.5 mol% 3HHx or 51% poly(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3-hydroxyoctanoate) consisting of 82 mol% 3HHx and 16 mol% of 3HO during a two-step cultivation process under nitrogen limitation when grown on sodium hexanoate or sodium octanoate. The two polyesters containing high percentage of 3HHx are physically characterized. They could be used as biodegradable pressure sensitive adhesives, coatings, polymer binding agents in organic-solvent-free paints or a source for chiral R-3-hydroxyhexanoate., ((c) 2010 Elsevier Ltd. All rights reserved.)

Pseudomonas putida KT2442 is a medium-chain-length polyhydroxyalkanoates (PHA) producer. One of the main shortages in the production of PHA has been the intracellular PHA degradation caused by its endogenous PHA depolymerase. The aim of this study was to improve PHA production via removing the PHA degradation mechanism. PHA depolymerase phaZ knockout mutant P. putida KTMQ01 was successfully constructed, which accumulated 86 wt% medium-chain-length PHA (mcl PHA) when cultured in mineral medium containing sodium octanoate as the carbon source compared with P. putida KT2442 which produced only 66 wt% of its cell dry weight (CDW). P. putida KTMQ01 cultured over a five-day period on sodium octanoate produced 4.5 g L(-1)-4.0 g L(-1) CDW containing approximately 80 wt% PHA without degradation. In contrast, P. putida KT2442 was observed with decreasing CDW and PHA from over 4 to less than 2 g L(-1) over the same period of time, indicating the function of PHA depolymerases which reduced the amount of PHA from around 50 wt% to none over the incubation period. RT-PCR analysis showed that phaC2 transcriptional level of P. putida KTMQ01 was higher than that of P. putida KT2442, indicating the possibility of relief on negative control of phaC2 transcription by the deletion of phaZ, which combined with the lack of in vivo PHA degradation, led to more PHA accumulation. P. putida KTMQ01 contained PHA granules with larger sizes and smaller numbers than those of P. putida KT2442.

Nine anaerobic promoters were cloned and constructed upstream of PHB synthesis genes phbCAB from Ralstonia eutropha for the micro- or anaerobic PHB production in recombinant Escherichia coli. Among the promoters, the one for alcohol dehydrogenase (PadhE) was found most effective. Recombinant E. coli JM 109 (pWCY09) harboring PadhE and phbCAB achieved a 48% PHB accumulation in the cell dry weight after 48 h of static culture compared with only 30% PHB production under its native promoter. Sixty-seven percent PHB was produced in the dry weight (CDW) of an acetate pathway deleted (Deltapta deletion) E. coli JW2294 harboring the vector pWCY09. In a batch process conducted in a 5.5-l NBS fermentor containing 3 l glucose LB medium, E. coli JW2294 (pWCY09) grew to 7.8 g/l CDW containing 64% PHB after 24 h of microaerobic incubation. In addition, molecular weight of PHB was observed to be much higher under microaerobic culture conditions. The high activity of PadhE appeared to be the reason for improved micro- or anaerobic cell growth and PHB production while high molecular weight contributed to the static culture condition.

Monomers of microbial polyhydroxyalkanoates, mainly 3-hydroxyhexanoic acid (3HHx) and 3-hydroxyoctanoic acid (3HO), were produced by overexpressing polyhydroxyalkanoates depolymerase gene phaZ, together with putative long-chain fatty acid transport protein fadL of Pseudomonas putida KT2442 and acyl-CoA synthetase (fadD) of Escherichia coli MG1655 in P. putida KT2442. FadL(Pp), which is responsible for free fatty acid transportation from the extracellular environment to the cytoplasm, and FadD(Ec), which activates fatty acid to acyl-CoA, jointly reinforce the fatty acid beta-oxidation pathway. Pseudomonas putida KT2442 (pYZPst01) harboring polyhydroxyalkanoates depolymerase gene phaZ of Pseudomonas stutzeri 1317 produced 1.37 g L(-1) extracellular 3HHx and 3HO in shake flask studies after 48 h in the presence of sodium octanoate as a sole carbon source, while P. putida KT2442 (pYZPst06) harboring phaZ(Pst), fadD(Ec) and fadL(Pp) achieved 2.32 g L(-1) extracellular 3HHx and 3HO monomer production under the same conditions. In a 48-h fed-batch fermentation process conducted in a 6-L fermentor with 3 L sodium octanoate mineral medium, 5.8 g L(-1) extracellular 3HHx and 3HO were obtained in the fermentation broth. This is the first time that medium-chain-length 3-hydroxyalkanoic acids (mcl-3HA) were produced using fadL(Pp) and fadD(Ec) genes combined with the polyhydroxyalkanoates depolymerase gene phaZ.