Dysbiosis and Staphylococcus species over representation in the exit site skin microbiota of hemodialysis patients carrying tunneled cuffed central venous catheter.

OBJECTIVES: Hemodialysis patients with end-stage renal disease (ESRD) are susceptible to infections and dysbiosis. Catheter-related infections are typically caused by opportunistic skin pathogens. This study aims to compare the skin microbiota changes around the exit site of tunneled cuffed catheters (peri-catheter group) and the contralateral site (control group). METHODS: ESRD patients on hemodialysis were recruited. The skin microbiota were collected with moist skin swabs and analyzed using high-throughput sequencing of the 16S rDNA V3-V4 region. After denoising, de-replication, and removal of chimeras, the reads were assigned to zero-radius operational taxonomic units (ZOTU). RESULTS: We found significantly reduced alpha diversity in the peri-catheter group compared to the control group, as indicated by the Shannon, Jost, and equitability indexes, but not by the Chao1 or richness indexes. Beta diversity analysis revealed significant deviation of the peri-catheter microbiota from its corresponding control group. There was an overrepresentation of Firmicutes and an underrepresentation of Actinobacteria, Proteobacteria, and Acidobacteria at the phylum level in the peri-catheter group. The most abundant ZOTU (Staphylococcus spp.) drastically increased, while Cutibacterium, a commensal bacterium, decreased in the peri-catheter group. Network analysis revealed that the skin microbiota demonstrated covariance with both local and biochemical factors. CONCLUSIONS: In conclusion, there was significant skin microbiota dysbiosis at the exit sites compared to the control sites in ESRD dialysis patients. Managing skin dysbiosis represents a promising target in the prevention of catheter-related bacterial infections.

Expression profiles and function prediction of tRNA-derived fragments in glioma.

BACKGROUND: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. METHODS: The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3'UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively. RESULTS: tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3'UTR. CONCLUSION: tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3'UTR.

CircMTA1 promotes glioblastoma angiogenesis by encoding MTA1-134aa.

Glioblastoma multiforme (GBM) is the most malignant brain tumor with rapid angiogenesis. How to inhibit GBM angiogenesis is a key problem to be solved. To explore the targets of inhibiting GBM angiogenesis, this study confirmed that the expression of circMTA1 (hsa_circ_0033614) was significantly upregulated in human brain microvascular endothelial cells exposed to glioma cell-conditioned medium (GECs). The expression of circMTA1 in the cytoplasm was significantly higher than that in the nucleus. Upregulated circMTA1 in GECs can promote cell proliferation, migration, and tube formation. Further exploration of the circularization mechanism of circMTA1 confirmed that KHDRBS1 protein can bind to the upstream and downstream flanking sequences of circMTA1 and promote circMTA1 biogenesis by coordinating Alu element pairing. KHDRBS1 upregulated the proliferation, migration, and tube formation of GECs by promoting the biogenesis of circMTA1. CircMTA1 can encode the protein MTA1-134aa by internal ribosome entry site sequence-mediated translation mechanism, and promote the proliferation, migration, and tube formation of GECs through the encoded MTA1-134aa. This study provides a new target for inhibiting angiogenesis in brain GBM and a new strategy for improving the therapeutic efficacy of GBM.

Neuroprotective effect of salidroside on hippocampal neurons in diabetic mice via PI3K/Akt/GSK-3ß signaling pathway.

BACKGROUND: Diabetic encephalopathy is manifested by cognitive dysfunction. Salidroside, a nature compound isolated from Rhodiola rosea L, has the effects of anti-inflammatory and antioxidant, hypoglycemic and lipid-lowering, improving insulin resistance, inhibiting cell apoptosis, and protecting neurons. However, the mechanism by which salidroside alleviates neuronal degeneration and improves learning and memory impairment in diabetic mice remains unclear. OBJECTIVE: To investigate the effects and mechanisms of salidroside on hippocampal neurons in streptozotocin-induced diabetic mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into 4 groups to receive either sham (control group (CON)), diabetes mellitus (diabetes group (DM)), diabetes mellitus + salidroside (salidroside group (DM + SAL)), and diabetes mellitus + salidroside + phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (diabetes mellitus + salidroside + LY294002 group (DM + SAL + LY294002)). After 12 weeks of diabetes onset, the cognitive behaviors were tested using Morris water maze. The number of hippocampal neurons was detected by Nissl staining. The expressions of PI3K, p-PI3K, Akt, p-Akt, GSK-3ß, p-GSK-3ß, cleaved caspase-3, caspase-3, Bax, Bcl-2, MAP2, and SYN in the hippocampus were detected by Western blot. Moreover, the expression of MAP2 and SYN in the hippocampus was further confirmed by immunofluorescence staining. RESULTS: Salidroside increased the time of diabetic mice in the platform quadrant and reduced the escape latency of diabetic mice. Salidroside also increased the expression of p-PI3K, p-Akt, p-GSK-3ß, MAP2, SYN, Bcl-2, while suppressed the expression of cleaved caspase-3, caspase3, and Bax in the DM + SAL group compared with the DM group (P < 0.05). The Nissl staining showed that the number of hippocampus neurons in the DM + SAL group was increased with the intact, compact, and regular arrangement, compared with the DM groups (P < 0.05). Interestingly, the protective effects of salidroside on diabetic cognitive dysfunction, hippocampal morphological alterations, and protein expressions were abolished by inhibition of PI3K with LY294002. CONCLUSIONS: Salidroside exerts neuroprotective properties in diabetic cognitive dysfunction partly via activating the PI3K/Akt/GSK-3ß signaling pathway.

Deep Learning for Predicting Distant Metastasis in Patients with Nasopharyngeal Carcinoma Based on Pre-Radiotherapy Magnetic Resonance Imaging.

IMPORTANCE: Accurate pre-treatment prediction of distant metastasis in patients with Nasopharyngeal Carcinoma (NPC) enables the implementation of appropriate treatment strategies for high-risk individuals. PURPOSE: To develop and assess a Convolutional Neural Network (CNN) model using pre-therapy Magnetic Resonance (MR) imaging to predict distant metastasis in NPC patients. METHODS: We retrospectively reviewed data of 441 pathologically diagnosed NPC patients who underwent complete radiotherapy and chemotherapy at Renmin Hospital of Wuhan University (Hubei, China) between February 2012 and March 2018. Using Adobe Photoshop, an experienced radiologist segmented MR images with rectangular regions of interest. To develop an accurate model according to the primary tumour, Cervical Metastatic Lymph Node (CMLN), the largest area of invasion of the primary tumour, and image segmentation methods, we constructed intratumoural and intra-peritumoural datasets that were used for training and test of the transfer learning models. Each model's precision was assessed according to its receiver operating characteristic curve and accuracy. Generated high-risk-related Grad-Cams demonstrated how the model captured the image features and further verified its reliability. RESULTS: Among the four models, all intra-peritumoural datasets performed better than the corresponding intratumoural datasets, with the CMLN intra-peritumoural dataset exhibiting the best performance (average area under the curves (AUCs) = 0.88). There was no significant difference between average AUCs of the Max and NPC tumour datasets. AUCs of the eight datasets for the four models were higher than those of the Tumour-Node-Metastasis staging system (AUC=0.67). In most datasets, the xception model had higher AUCs than other models. The efficientnet-b0 and xception models efficiently extracted high-risk features. CONCLUSION: The CNN model predicted distant metastasis in NPC patients with high accuracy. Compared to the primary tumour, the CMLN better predicted distant metastasis. In addition to intratumoural data, peritumoural information can facilitate the prediction of distant metastasis. With a larger sample size, datasets of the largest areas of tumour invasion may achieve meaningful accuracy. Among the models, xception had the best overall performance.

Association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid and preterm delivery in women / 北京大学学报(医学版)

OBJECTIVE@#To explore the association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid(MMFA) and risk of preterm delivery in women with natural conception, singleton pregnancy and vaginal delivery.@*METHODS@#A retrospective cohort study was performed based on the prenatal health care system and hospital information system of Tongzhou Maternal and Child Health Hospital of Beijing and the women who had their prenatal care in the hospital from January 2015 to December 2018 were included. The information of 16 332 women who conceived naturally, had a singleton pregnancy, and delivered vaginally was collected. Compliance scores were constructed based on the time of initiation and the frequency of taking nutritional supplements. The association between maternal periconceptional micronutrient supplementation, including pure folic acid (FA) pills or MMFA and the rate of preterm delivery was evaluated using Logistic regression models.@*RESULTS@#The preterm delivery rate (gestational week < 37 weeks) of the study population was 3.8%, and the mean (standard deviation) of gestational age was (38.98±1.37) weeks. A total of 6 174 (37.8%) women took FA during the periconceptional period, 8 646 (52.9%) women took MMFA, and 1 512 (9.3%) women did not take any nutritional supplements. The association between periconceptional supplementation of FA or MMFA and risk of preterm delivery in women was not statistically significant [adjusted odds ratio (aOR)=1.01, 95%CI: 0.74-1.37]. The associations with preterm birth were not statistically significant in further analysis by the type of nutritional supplements, time of initiation, and the frequency of supplementation. In addition, the association between the compliance score of taking supplements and the rate of preterm delivery was not statistically significant, either.@*CONCLUSION@#This study did not find an association between the risk of preterm delivery and the use of FA or MMFA during the periconcep-tional period in women with natural conception, singleton pregnancy, and vaginal delivery. In the future, multicenter studies with large-scale prospective cohort or population-based randomized controlled trials are warranted to confirm the association between taking FA or MMFA during the periconceptional period and preterm delivery among women.

A Multicenter Randomized Trial Assessing ZENFlow Carrier-Free Drug-Coated Balloon for the Treatment of Femoropopliteal Artery Lesions.

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

Characterization of Changes and Driver Microbes in Gut Microbiota During Healthy Aging Using A Captive Monkey Model.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.

Analysis of the current status of knowledge, attitude and practice of metabolic syndrome and its influencing factors among the elderly in Beijing community / 中华老年医学杂志

Objective:To understand the status of knowledge, attitude and practice of metabolic syndrome(MS) among the elderly in the community and analyze its influencing factors, so as to provide guidance for the prevention and treatment of MS.Methods:From January 2021 to August 2021, permanent residents(residence duration ≥6 months)aged 65 and above with regular health check examination in Fangzhuang Community Health Service Center of Fengtai District, Beijing were investigated using self-designed MS knowledge, attitude and practice questionnaire.After excluding 34 incomplete questionnaires, the 491 valid questionnaires were recycled with questionnaire valid percentage of 93.5%(491/525). The survey results were analyzed by descriptive analysis, Mann-Whitney U test, Kruskal-Wallis H test and multiple linear regression analysis and multiple linear regression.Results:The scores of MS knowledge, attitude and practice of the elderly in the community were 7(5, 10), 9(8, 10)and 19(18, 21)respectively.The correct answer rate of the diagnostic criteria of MS components was less than 50%.The score of knowledge about MS in the elderly was positively correlated with the scores of attitudes( r=0.263)and practice( r=0.134)(all P<0.01). The results of univariate and multiple linear regression analysis showed that gender, attending educational lectures and the prevalence of MS were the influencing factors of MS knowledge score(all P<0.05). Leisure time, attending educational lectures, pre-retirement occupation and regular health check examination were the influencing factors for MS attitude score(all P<0.05); attending educational lectures, leisure time, regular health check examination and pre-retirement occupation were the influencing factors for MS practice score(all P<0.05). Conclusions:The elderly in the community have a low level of knowledge about the components and diagnostic criteria of MS, but have a positive attitude and practice towards the prevention and treatment of MS.The level of knowledge, attitude and practice of MS is affected by health education lectures, occupation, regular health check examination and other factors.Health education on the diagnostic criteria and the awareness of disease prevention for the elderly in the community should be strengthened to improve the levels of the knowledge, attitude and practice of MS.

Valuing Personal Data with Privacy Consideration.

A key challenge in information privacy research is how to value personal data with privacy consideration. In this study, we propose an experimental auction approach for valuing personal data. We use the generalized second-price auction to assess the monetary values of individuals' identity, demographic, and private information. We find that individuals' economic valuation of personal data is consistent with their actual self-disclosure behaviors. The economic valuation approach also produces results that are consistent with some well-accepted observations about consumer demographics and privacy. On the other hand, individuals' stated privacy preferences and attitudes are not consistent with their economic valuation. The findings of this study suggest that the proposed approach can be an effective mechanism for measuring personal data privacy. This study also provides important insights into valuing personal information for practical uses with several implications to policy decision makers, corporate executives and managers, data analysts, as well as decision science researchers.

Determining 5HT7R's Involvement in Modifying the Antihyperalgesic Effects of Electroacupuncture on Rats With Recurrent Migraine.

Electroacupuncture (EA) is widely used in clinical practice to relieve migraine pain. 5-HT7 receptor (5-HT7R) has been reported to play an excitatory role in neuronal systems and regulate hyperalgesic pain and neurogenic inflammation. 5-HT7R could influence phosphorylation of protein kinase A (PKA)- or extracellular signal-regulated kinase1 / 2 (ERK1 / 2)-mediated signaling pathways, which mediate sensitization of nociceptive neurons via interacting with cyclic adenosine monophosphate (cAMP). In this study, we evaluated the role of 5-HT7R in the antihyperalgesic effects of EA and the underlying mechanism through regulation of PKA and ERK1 / 2 in trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC). Hyperalgesia was induced in rats with dural injection of inflammatory soup (IS) to cause meningeal neurogenic inflammatory pain. Electroacupuncture was applied for 15 min every other day before IS injection. Von Frey filaments, tail-flick, hot-plate, and cold-plated tests were used to evaluate the mechanical and thermal hyperalgesia. Neuronal hyperexcitability in TNC was studied by an electrophysiological technique. The 5-HT7R antagonist (SB269970) or 5-HT7R agonist (AS19) was administered intrathecally before each IS application at 2-day intervals during the 7-day injection protocol. The changes in 5-HT7R and 5-HT7R-associated signaling pathway were examined by real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) analyses. When compared with IS group, mechanical and thermal pain thresholds of the IS + EA group were significantly increased. Furthermore, EA prevented the enhancement of both spontaneous activity and evoked responses of second-order trigeminovascular neurons in TNC. Remarkable decreases in 5-HT7R mRNA expression and protein levels were detected in the IS + EA group. More importantly, 5-HT7R agonist AS19 impaired the antihyperalgesic effects of EA on p-PKA and p-ERK1 / 2. Injecting 5-HT7R antagonist SB-269970 into the intrathecal space of IS rats mimicked the effects of EA antihyperalgesia and inhibited p-PKA and p-ERK1 / 2. Our findings indicate that 5-HT7R mediates the antihyperalgesic effects of EA on IS-induced migraine pain by regulating PKA and ERK1 / 2 in TG and TNC.

Analysis of standard accounting method of economic compensation for ecological pollution in watershed.

With rapid development of social industry and agriculture, there is an increasing demand for water resources in a watershed, which leads to a series of serious problems in the watershed such as water resource shortage, water environment deterioration, water resource pollution, etc. This paper builds an econometric model of economic loss due to water pollution in a watershed based on the basic process of standard water pollution compensation calculation of economic loss. The econometric model is used to calculate the amount of compensation for economic loss due to water pollution; a mathematic model method of water environment is applied to calculate the degree of effect on the lower reaches; thus the proportion of the impact on the areas in the lower reaches to overall impact is obtained. The amount of compensation that should be borne by all areas is obtained in combination of amount of compensation for water pollution. Empirical analysis is carried out by taking the Taihu Basin for example, and the standard compensation and the amount of compensation for the economic loss caused by water pollution between different areas along the Jiangnan Canal in the Taihu Basin are defined, which provides scientific and theoretical bases for standard calculation of the water pollution compensation. This provides a theoretical basis for solving the problem of water pollution in the watershed and the contradiction in the development of the watershed, and realizing social equity and harmonious development.

[Research of inflammatory factors and signaling pathways in knee osteoarthritis].

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 ß, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-ß pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.

[Effect of fire-needle intervention on joint function, cartilage impairment and inflammatory response in knee osteoarthritis rats].

OBJECTIVE: To observe the effect of fire-needle stimulation of "Neixiyan"(EX-LE4) and "Dubi"(ST35) on changes of motor function, structure of cartilage degradation and inflammatory factors in knee osteoarthritis (KOA) rats, so as to explore its underlying mechanisms in improving KOA. METHODS: Thirty-nine male SD rats were randomly divided into normal, model and fire-needle groups (n＝13 in each group). The KOA model was established by injection of Monoiodoacetate (MIA, 1 mg) into the lumen of the right knee joint. On the 7th day after successful modeling, fire-needle was applied to EX-LE4 and ST35, twice a week for 3 weeks. The rats' behavioral reactions of gait (0 to 3 points) and claw pressure (0 to 3 points) were scored, and histopathological changes scored by assessing the impairment grade (0 to 6) and stage (0 to 4) of the articular cartilage after safranin O-fast green staining. The contents of serum Interleukin (IL)-1α， Tumor necrosis factor α(TNF-α), IL-10, IL-37 and transforming growth factor ß(TGF-ß) were assayed by ELISA, and ultrastructural changes were observed under transmission electron microscope(TEM). RESULTS: After modeling, the gait and claw-pressure scores were significantly increased in the model group in comparison with the normal group (P<0.05), and the OA score and contents of serum IL-1α and TNF-α were also appa-rently increased in the model group relevant to the normal group (P<0.05，P<0.01), while the levels of serum IL-10, IL-37 and TGF-ß remarkably decreased in the model group in contrast to the normal group (P<0.01). After the intervention, the increase of gait and claw-pressure and OA scores, as well as serum IL-1α and TNF-α contents, and the decrease of serum IL-10, IL-37 and TGF-ß levels were all reversed in the fire needle group (P<0.05, P<0.01). Outcomes of TEM showed more and larger lipid droplets, swollen mitochondria with some vacuoles, and expanded, broken or dissolved rough endoplasmic reticulum in the model group, which was milder in the fire-needle group. CONCLUSION: Fire-needle can improve motor function and relieve impairment of articular cartilage of KOA rats, which may be related to its effects in reducing inflammatory factors and in increasing anti-inflammatory factor levels.

Protecting Privacy When Sharing and Releasing Data with Multiple Records per Person.

This study concerns the risks of privacy disclosure when sharing and releasing a dataset in which each individual may be associated with multiple records. Existing data privacy approaches and policies typically assume that each individual in a shared dataset corresponds to a single record, leading to an underestimation of the disclosure risks in multiple records per person scenarios. We propose two novel measures of privacy disclosure to arrive at a more appropriate assessment of disclosure risks. The first measure assesses individual-record disclosure risk based upon the frequency distribution of individuals' occurrences. The second measure assesses sensitive-attribute disclosure risk based upon the number of individuals affiliated with a sensitive value. We show that the two proposed disclosure measures generalize the well-known k-anonymity and l-diversity measures, respectively, and work for scenarios with either a single record or multiple records per person. We have developed an efficient computational procedure that integrates the two proposed measures and a data quality measure to anonymize the data with multiple records per person when sharing and releasing the data for research and analytics. The results of the experimental evaluation using real-world data demonstrate the advantage of the proposed approach over existing techniques for protecting privacy while preserving data quality.

Predictive Analytics with Strategically Missing Data.

We study strategically missing data problems in predictive analytics with regression. In many real-world situations, such as financial reporting, college admission, job application, and marketing advertisement, data providers often conceal certain information on purpose in order to gain a favorable outcome. It is important for the decision-maker to have a mechanism to deal with such strategic behaviors. We propose a novel approach to handle strategically missing data in regression prediction. The proposed method derives imputation values of strategically missing data based on the Support Vector Regression models. It provides incentives for the data providers to disclose their true information. We show that with the proposed method imputation errors for the missing values are minimized under some reasonable conditions. An experimental study on real-world data demonstrates the effectiveness of the proposed approach.

One-Step Dip-Coating-Fabricated Core-Shell Silk Fibroin Rice Paper Fibrous Scaffolds for 3D Tumor Spheroid Formation.

Bioscaffolds are important substrates for supporting three-dimensional (3D) cell cultures. Silk fibroin (SF) is an attractive biomaterial in tissue engineering because of its good biocompatibility and mechanical properties. Electrospinning is one of the most often used approaches to fabricate SF fibrous scaffolds; yet, this technique still faces many challenges, such as low yield, residual organic solvents, limited extensibility of fibers, and a lack of spatial control over pore size. To circumvent these limitations, a core-shell SF on rice paper (SF@RP) fibrous scaffold was fabricated using a mild one-step dip-coating method. The cellulose fiber matrix of RP is the physical basis of the 3D scaffold, whereas the SF coating on the cellulose fiber controls the adhesion/spreading of the cells. The results indicated that by tuning the secondary structure of SF on the surface of a SF@RP scaffold, the cell behavior on SF@RP could be tuned. Tumor spheroids can be formed on SF@RP scaffolds with a dominant random secondary structure, in contrast to cells adhering and spreading on SF@RP scaffolds with a higher ratio of ß-sheet secondary structures. Direct culturing of breast cancer MDA-MB-231 and MCF-7, lung cancer A549, prostate cancer DU145, and liver cancer HepG2 cells could spontaneously lead to corresponding tumor spheroids on SF@RP. In addition, the physiological characteristics of HepG2 tumor spheroids were investigated, and the results showed that compared with HepG2 monolayer cells, CYP3A4, CYP1A1, and albumin gene expression levels in HepG2 cell spheres formed on SF@RP scaffolds were significantly higher. Moreover, these spheroids showed higher drug resistance. In summary, these SF@RP scaffolds prepared by the dip-coating method are biocompatible substrates for cell culture, especially for tumor cell spheroid formation.

Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson's disease: a meta-analysis.

BACKGROUND: Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson's disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson's disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality. RESULTS: Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD - 7.00, 95% CI - 8.35 to - 5.65, P < 0.00001) for total UPDRS score (nine trials; MD - 5.74, 95% CI - 7.71 to - 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD - 1.61, 95% CI - 2.18 to - 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD - 0.38, 95% CI - 0.61 to - 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD - 5.71, 95% CI - 7.11 to - 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83-3.00, P = 0.16). CONCLUSIONS: S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

Chromosomal aberrations detection in chronic lymphocytic leukemia by conventional cytogenetics using DSP30 and IL-2 / 中华血液学杂志

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion: DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Roles of Probiotic Supplementation in the Prevention and Treatment of Asthma:A Systematic Review / 中国医学科学院学报

To systematically review the effects of probiotic supplementation on the prevention and treatment of asthma. A computerized literature search was conducted in CNKI,CBM,VIP,Wanfang,PubMed,Embase,Cochrane Library,and Web of Science from their inception to February,2019 to collect all relevant studies. Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the included studies. Twelve studies were included in the systematic review of the value of probiotics in asthma prevention. The results showed that probiotic supplementation was not significantly associated with a lower risk of asthma (=0.95,95%=0.82-1.11) or wheeze (=0.99,95%=0.88-1.11). Subgroup analyses based on interventions did not show significant differences. Six studies were included in the systematic review of the role of probiotics in asthma treatment. The results showed that probiotic supplementation improved pulmonary function and asthma control in asthmatic patients. However,more studies are needed to validate this effect. Moreover,further studies are needed to clarify the effect of probiotics on the immune markers and the use of asthmatic drugs in asthmatic patients. Based on the currently available literature,probiotic supplementation can not prevent asthma or wheeze. However,it may improve pulmonary function and asthma control in asthmatic patients,although further studies are needed.