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To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P

Ligusticum L., one of the largest members in Apiaceae, encompasses medicinally important plants, the taxonomic statuses of which have been proved to be difficult to resolve. In the current study, the complete chloroplast genomes of seven crucial plants of the best-known herbs in Ligusticum were presented. The seven genomes ranged from 148,275 to 148,564 bp in length with a highly conserved gene content, gene order and genomic arrangement. A shared dramatic decrease in genome size resulted from a lineage-specific inverted repeat (IR) contraction, which could potentially be a promising diagnostic character for taxonomic investigation of Ligusticum, was discovered, without affecting the synonymous rate. Although a higher variability was uncovered in hotspot divergence regions that were unevenly distributed across the chloroplast genome, a concatenated strategy for rapid species identification was proposed because separate fragments inadequately provided variation for fine resolution. Phylogenetic inference using plastid genome-scale data produced a concordant topology receiving a robust support value, which revealed that L. chuanxiong had a closer relationship with L. jeholense than L. sinense, and L. sinense cv. Fuxiong had a closer relationship to L. sinense than L. chuanxiong, for the first time. Our results not only furnish concrete evidence for clarifying Ligusticum taxonomy but also provide a solid foundation for further pharmaphylogenetic investigation.

Blastocystis, an enteric protist, has been reported to be an important cause of protozoal gastrointestinal manifestations in humans and animals worldwide. Animals harboring certain Blastocystis subtypes (STs) may serve as a potential source of human infection. However, information about the prevalence and genetic diversity of Blastocystis in alpacas is limited. In the present study, a total of 366 fecal samples from alpacas in Shanxi Province, northern China, were examined for Blastocystis by PCR amplification of the small subunit rRNA gene, followed by sequencing and phylogenetic analysis. The prevalence of Blastocystis in alpacas was 23.8%, and gender difference in the prevalence of Blastocystiswas observed. The most predominant Blastocystis ST was ST10, followed by ST14 and ST5. The detection of ST5, a potentially zoonotic genotype, indicates that alpacas harboring ST5 could be a potential source of human infection with Blastocystis. These data provide new insight into the prevalence and genetic diversity of Blastocystis in alpacas.

Cysticercus pisiformis, the larval stage of Taenia pisiformis, causes serious illness in rabbits that severely impacts the rabbit breeding industry. An inhibitive Th2 immune response can be induced by let-7-enriched exosomes derived from T. pisiformis cysticercus. However, the underlying molecular mechanisms are not completely understood. Here, we report that exosomal miR-let-7-5p released by T. pisiformis cysticercus played a critical role in the activation of M2 macrophages. We found that overexpression of let-7-5p in M1 macrophages decreased M1 phenotype expression while promoting polarization to the M2 phenotype, which is consistent with experimental data in exosome-treated macrophages alone. In contrast, knockdown of let-7-5p in exosome-like vesicles promoted M1 polarization and decreased M2 phenotype expression. Furthermore, down-regulation of transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ resulted in the decrease of M1 phenotype markers and increase of M2 phenotype markers. These results suggested that let-7 enriched in exosome-like vesicles from T. pisiformis metacestodes can induce M2 macrophage polarization via targeting C/EBP δ, which may be involved in macrophage polarization induced by T. pisiformis metacestodes. The finding helps to expand our knowledge of the molecular mechanism of immunosuppression and Th2 immune response induced by metacestodes.

Purpose We aimed to assess the awareness of interventional radiology (IR) among medical students, and to evaluate an IR curriculum in China. Methods Between the academic years of 2008 and 2016, 517 third-year medical undergraduates, who successfully applied for an IR curriculum, received a survey related to IR before taking the course. Final exams were conducted after the IR course. Results A total of 355 of the 517 medical students (68.67%) answered the survey; 81.97% of the respondents had heard of IR, 40.28% believed they understood what IR is, but no one was familiar with IR. The four most common pathways for medical students to acquire IR knowledge were via new media (e.g., internet, apps) (42.82%), a teacher/textbook (36.90%), a friend (32.68%), and traditional media (26.48%). The most familiar interventional procedures to respondents were percutaneous transluminal coronary angioplasty (PTCA, 78.59%) and transcatheter arterial chemoembolization (TACE, 44.51%). The results of the survey also indicated that 68.45% of the respondents wanted to learn about IR, but that only 47 male students (13.24%) considered a career in IR. The pass rate of the IR course final exam was 87.04%, i.e., 87.04% of the students successfully completed the course and final exam. Conclusion The IR knowledge of medical students in China is worse than that of European medical students. We suggest that providing medical students with general information about IR in the media, as well as via teaching and textbooks in medical school, requires prompt and significant attention. An IR curriculum is beneficial for increasing the IR knowledge of undergraduates.

Enterocytozoon bieneusi is a zoonotic parasite which is considered to be an opportunistic pathogen of humans and animals. A number of studies have reported E. bieneusi infection in various animals. However, no information is available on the occurrence of E. bieneusi in Tan sheep, a unique indigenous sheep species in the Ningxia Hui Autonomous Region, China. The objectives of the present study were to examine the prevalence and identify the genotypes of E. bieneusi in Tan sheep in China. A total of 1014 fecal specimens of Tan sheep from six farms in the Ningxia Hui Autonomous Region were examined by nested PCR amplification of the internal transcribed spacer (ITS) of nuclear ribosomal DNA. The total prevalence of E. bieneusi was 12.2% (124/1014), ranging from 0.5 to 22.2% on six farms. Sequence analysis identified 10 genotypes of E. bieneusi, including three known genotypes, BEB6, COS-I, and CHG13, and seven novel genotypes designated as NX1 to NX7, which all belonged to group 2 by phylogenetic analysis. This is the first report describing the prevalence of E. bieneusi in Tan sheep, and the new genotypes identified in the current study expand the genotype distribution of E. bieneusi. These findings provide baseline data and have implications for the epidemiology and control of E. bieneusi infection in Tan sheep.

To investigate the association of family history of malignant tumors with clinicopathological characteristics of colorectal cancer, and its effects on prognosis. We conducted a retrospective review of pathological and follow-up data of patients with colorectal cancer treated in our hospital from January 2010 to December 2015. Of 870 patients undergoing surgery, 737 received follow-up (84.7%). Among them, 192 (26.1%) were family history of malignant neoplasm-positive [MN-FH (+)] and 545 (73.9%) were family history of malignant neoplasm-negative [MN-FH (-)]. MN-FH (+) patients had earlier disease onset, smaller tumor diameter, lower rate of lymph node metastasis, and lower depth of invasion. There were significant differences in BMI between the groups (P0.05) but no differences in sex or tumor differentiation grade (P0.05). Rates of Her-2 and p53 protein expression in MN-FH (+) patients were 34.3 and 40.5%, respectively, compared with 22.2 and 26.3% in MN-FH (-) patients. In stage 3, significantly higher Her-2 and p53 protein expression rates were observed in MN-FH (+) than in MN-FH (-) patients. Fluorescence in-situ hybridization showed significantly higher Her-2 expression in MN-FH (+) than in MN-FH (-) patients. The 3 and 5-year overall survival, disease-free survival, and progression-free survival were significantly lower in MN-FH (+) than in MN-FH (-) patients (P0.05). MN-FH (+) patients with colorectal cancer had earlier disease onset and smaller tumor area, lower invasion depth, a lower rate of lymph node metastasis, and earlier TNM tumor stage at diagnosis than MN-FH (-) patients. BMI value distribution significantly differed between groups. However, long-term prognosis was worse for MN-FH (+) than MN-FH (-) patients, suggesting that internal pathogenic genes play a more crucial role than external environmental factors in prognosis. Family history of tumors could be an independent prognostic factor for colon cancer.

Yunling cattle is an unique cattle breed distributed in Yunnan Province, southwestern China. It is yet to know whether Yunling cattle are infected with Giardia duodenalis and Cryptosporidium spp.. The objectives of the present study were to investigate the prevalence and characterize the assemblages of G. duodenalis and species of Cryptosporidium spp. in Yunling cattle in Yunnan province. The overall prevalence of G. duodenalis and Cryptosporidium spp. were 10.49% (41/391) and 0.77% (3/391), respectively. The age was considered as the risk factor for Yunling cattle infection with G. duodenalis (χ2 = 8.082, OR = 2.56, P = 0.004). Two assemblages of G. duodenalis, assemblage A (n = 1) and assemblage E (n = 40), were identified by amplification of the β-giardin (bg) and glutamate dehydrogenase (gdh) gene loci using the nested PCR methods. Furthermore, Cryptosporidium andersoni (n = 1) and Cryptosporidium ryanae (n = 2) were detected by nested PCR targeting the small subunit (SSU) rRNA gene. This is the first report of G. duodenalis and Cryptosporidium spp. in Yunling cattle in China, which provided baseline date for further studies of the prevalence, genetic identity, and public health potential of these parasites in Yunling cattle.

PurposeTo extract texture features from magnetic resonance imaging (MRI) scans of patients with brain tumors and use them to train a classification model for supporting an early diagnosis.MethodsTwo groups of regions (control and tumor) were selected from MRI scans of 40 patients with meningioma or glioma. These regions were analyzed to obtain texture features. Statistical analysis was conducted using SPSS (version 20.0), including the Shapiro–Wilk test and Wilcoxon signed-rank test, which were used to test significant differences in each feature between the tumor and healthy regions. T-distributed stochastic neighbor embedding (t-SNE) was used to visualize the data distribution so as to avoid tumor selection bias. The Gini impurity index in random forests (RFs) was used to select the top five out of all features. Based on the five features, three classification models were built respectively with three machine learning classifiers: RF, support vector machine (SVM), and back propagation (BP) neural network.ResultsSixteen of the 25 features were significantly different between the tumor and healthy areas. Through the Gini impurity index in RFs, standard deviation, first-order moment, variance, third-order absolute moment, and third-order central moment were selected to build the classification model. The classification model trained using the SVM classifier achieved the best performance, with sensitivity, specificity, and area under the curve of 94.04%, 92.3%, and 0.932, respectively.ConclusionTexture analysis with an SVM classifier can help differentiate between brain tumor and healthy areas with high speed and accuracy, which would facilitate its clinical application.

The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP-1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse-transcription polymerase chain reaction (RT-PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)-1α, and programmed death ligand-1 (PD-L1) as well as those of cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12, and IL-10. THP-1 macrophages and T cells were co-cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M2 marker CD163 (P

Pudendal nerve injuries are not an uncommon side effect of patient positioning on a traction table, and muscle relaxation has been suggested to mitigate this risk by reducing pressure on the perineum. A total of 40 patients scheduled for hip arthroscopic surgery under general anaesthesia were recruited. After induction of anaesthesia, pressures on the perineum were measured in 20 subjects by means of an ultra-thin pressure sensor mat wrapped around the perineal post. Perineal pressures were assessed after the induction of anaesthesia, after leg traction and after deep muscle relaxation. In 22 subjects, the hip joint width was measured radiographically at the same time points. Pressures on the perineum were high after traction (median maximum pressure 2540 g cm−2). Neuromuscular paralysis reduced perineal pressures only minimally, but significantly (−5 g cm−2; P = 0.007). Traction increased hip joint width significantly [mean 66 (12)%; P = 0.001) and muscle relaxation further increased joint width by a mean of 3.2 (0–20)% (P = 0.001). Muscle relaxation was more beneficial for male patients (joint width increase 6.8% versus 2.8%; P = 0.04), as well as patients in whom traction alone did not achieve sufficient joint width. Muscle relaxation reduced the perineal pressure during hip arthroscopic surgery by only a negligible amount. With regard to joint space, relaxation may be of highest benefit in male patients and/or patients in whom traction alone produces only a relatively small increase in joint width (trial registration: ANZCTR 12617000191392).

Background Taenia pisiformis is one of the most common intestinal parasites in canines, and leads to serious economic losses in the rabbit breeding industry. Exosome-like vesicles from parasites play crucial roles in host-parasite interactions by transferring cargo from parasites to host cells and by modulating host immunological response through inducing production of host-derived cytokines. Nevertheless, the mechanism by which exosome-like vesicles from T. pisiformis cysticercus regulate the macrophage immune response remains unknown. Methods Using ultracentrifugation, we isolated exosome-like vesicles from excretory/secretory products (ESP) of T. pisiformis cysticercus. The morphology and size of purified vesicles were confirmed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The components of proteins and miRNAs within these vesicles were identified by proteomic analysis and high-throughput small RNA sequencing. The biological function of targets of exosomal miRNAs was predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Moreover, the expression of Th1- and Th2-type immune response associated cytokines in RAW264.7 macrophages were evaluated by qPCR and ELISA. We found that exosome-like vesicles were typical cup-shaped vesicles with diameters from 30 to 150 nm. A total of 87 proteins were identified by proteomic analysis, including proteins prominently associated with exosome-like vesicles biogenesis and vesicle trafficking. 41 known miRNAs and 18 novel miRNAs were identified in the exosome-like vesicles. Eleven selected miRNAs, including 7 known miRNAs (miR-71-5p, miR-10a-5p, miR-let-7-5p, miR-745-3p, miR-219-5p, miR-124-3p and miR-4989-3p) and 4 novel miRNAs (novel-mir-3, novel-mir-7, novel-mir-8 and novel-mir-11) were validated to exist in metacestiodes and exosome-like vesicles of T. pisiformis cysticercus by qPCR. The functions of most targets of exosomal miRNAs were mainly associated with signal transduction and the immune system. Additionally, T. pisiformis cysticercus-derived vesicles induced the production of IL-4, IL-6, IL-10, IL-13 and Arg-1, but downregulated the expression of IL-12, IFN-γ and iNOS in RAW264.7 macrophages. Conclusions We demonstrated that proteins and miRNAs enclosed within exosome-like vesicles from T. pisiformis cysticercus have immunomodulatory functions. Furthermore, exosome-like vesicles were shown to induce the macrophage Th2-type immune response in vitro. Our study suggests that exosome-like vesicles play an important role in the interaction between cysticerci and their hosts.

BACKGROUND: Thyroid cancer is a common endocrine tumor, the incidence of which is increasing each year. Early diagnosis and treatment can effectively prevent thyroid cancer. This article uses Chinese’s ultrasound reports to determine the value of early diagnosis. METHODS: The clinical data center of the First Affiliated Hospital of Nanjing Medical University was screened for patients diagnosed with a thyroid nodule, who had undergone a thyroid function test, ultrasound records and pathological assessment. A total of 811 patients with a total of 1,290 pathologically confirmed nodules (506 benign and 784 malignant) were enrolled. Logistic regression was used to analyze the variables that significantly affected malignant nodules. The sensitivity and specificity of ultrasound thyroid imaging-reporting and data system (TI-RADS) classification results for benign and malignant tumors were calculated. RESULTS: The age of the patients had a very significant difference in the classification of benign and malignant nodules (P0.05). Thyroglobulin (TG), free thyroxine (FT4), and free triiodothyronine (FT3) had significant effects (P=0.003) on the incidence of malignant nodules in patients, while thyroid-stimulating hormone (TSH) had no significant effect (P>0.05). Ultrasound analysis showed a Youden’s index of 78.97%, a positive predictive value of 93.20%, and a negative predicted value of 84.10% at the most excellent classification effect. The sensitivity was 89.0%, the specificity was 89.9%; much greater than the classification model based on the thyroid function test (sensitivity =80.6%, specificity =55.8%). CONCLUSIONS: The present study verifies the effectiveness of using TI-RADS classification for diagnosis of benign and malignant thyroid nodules, and explores the use of new analysis methods for clinical data. To reduce dependence on the doctors, ultrasound image data and clinical phenotypic data can be further used to assist clinical decision making.

BACKGROUND: Evidence of a role for type 2 diabetes in overall cancer risk is limited in ethnic Chinese populations. We therefore investigated whether there is an association between diabetes and cancer incidence. METHODS: All type 2 diabetes and cancer hospitalized patients from the First Affiliated Hospital of Nanjing Medical University between 2006.01 and 2013.12 were eligible for the study. Our research used healthcare information technology and statistical methods to analyze the clinical data of hospitalized patients and explored the relationship between diabetes and cancer. Participants with fasting glucose ≥126 mg/dL, or taking hypoglycemic medications, were classed as having type 2 diabetes. Cancer incidence was established through regular follow-up interviews and medical records. Data were entered into Excel and a database was set up with ACCESS software. Clinical information such as demographics like gender, age, occupation, marriage, insurance and etc., diagnoses, and prescription record were chosen and analyzed. SPSS software was also used for statistical analysis. RESULTS: The number of patients with both diabetes and cancer rose from 220 cases in 2006 to 1,623 cases in 2013. The proportion of cancer patients with diabetes has also increased every year. Younger participants (aged ≤50 years) with diabetes had a greater risk of all cancers [P3.4]. And cancer patients with diabetes occurs more frequently in male patients than in female patients, especially since 2009 the proportion has increased more evidently (P1.4). Further analysis showed that the level of blood lipid in patients with diabetes mellitus and cancer was significantly different from that in patients with simple diabetes mellitus (P

Pancreatic cancer remains one of the most lethal human cancers without efficient therapeutic strategy. MicoRNAs (miRNAs) are a group of small non-coding RNAs involved in multiple biological processes including tumor development and progression. In this study, we investigated the expression and function of miR-4516 in pancreatic cancer. MiR-4516 was low-expressed in pancreatic cancer tissues and cell lines. Overexpression of miR-4516 inhibited pancreatic cancer cell proliferation, migration and invasion, while promoted cell apoptosis in vitro. Further, overexpression of miR-4516 suppressed xenograft pancreatic tumor growth in vivo. Bioinformatics analysis was performed and miR-4516 was predicted to negatively regulate orthodenticle homeobox 1 (OTX1) expression by binding to its 3'-UTR. Consistently, OTX1 was highly expressed in pancreatic cancer tissues and cell lines. Knockdown of OTX1 expression suppressed pancreatic cancer cell migration and invasion, with down-regulated MMP2 and MMP9 expression. Moreover, we demonstrated that miR-4516 regulated pancreatic cancer cell growth, migration, invasion and apoptosis via targeting OTX1. Overexpression of OTX1 could partially abrogate the inhibitory effect of miR-4516. Taken together, we conclude that miR-4516 could function as a tumor suppressor via targeting OTX1. These findings suggest that miR-4516/OTX1 axis might be a novel therapeutic target for miRNA-based therapy for pancreatic cancer patients.

Giardia duodenalis is a zoonotic enteric parasite that can infect humans and a number of animal species including rabbits with a worldwide distribution. Infection with G. duodenalis can cause serious public health problems and significant economic losses to animal husbandry. So accurate understanding of the prevalence and genotype distribution of G. duodenalis in rabbits is necessary. In the present study, a total of 616 fecal samples were collected from rabbits in Shandong province, eastern China, and examined in G. duodenalis prevalence and genotypes by nested PCR amplification of β-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi) gene loci of G. duodenalis. Sixty-nine (11.2%) of the examined rabbit fecal samples were G. duodenalis-positive. Of them, the prevalence of G. duodenalis is 8.4% (41/490) in Rizhao city and 22.2% (28/126) in Weihai city. Breeds, region, and feeding modes were highly correlated with G. duodenalis infection in rabbits. Moreover, three genotypes (assemblages A, B, and E) were identified in rabbits at three gene loci, and the assemblage E was the dominant genotype, while the assemblage A was reported in rabbits in China for the first time. It is noticeable that two rabbits were found to be infected with two different G. duodenalis assemblages (assemblages A and E, assemblages B and E, respectively). These findings enrich the genotype distribution of G. duodenalis in rabbits and provide baseline data for preventing and controlling G. duodenalis infection in rabbits in eastern China.

Eimeria spp. and Blastocystis are the common parasites that parasitize the intestinal tract of rabbits, which can seriously threaten the health of rabbits and lead to economic losses to the rabbit industry. However, information about the prevalence and transmission of these two parasites in rabbits is limited in China. The objective of this study was to survey the prevalence of Eimeria spp. and Blastocystis in rabbits in Shandong Province. A total of 616 rabbit fecal samples were collected from two cities (Rizhao and Weihai) in Shandong Province, eastern China, and Eimeria spp. and Blastocystis were identified by polymerase chain reaction based on species-specific markers. The prevalence of Eimeria spp. was 20% (123/616) and the Blastocystis prevalence was 0.97% (6/616). Five different Eimeria species (Eimeria intestinalis, E. perforans, E. magna, E. media, and E. irresidua) and the ST4 subtype of Blastocystis were identified in rabbits by sequence analysis. This is the first report of Blastocystis prevalence and subtype ST4 in rabbits in Shandong Province. The findings provide baseline data for the prevention and control of Eimeria spp. and Blastocystis in rabbits in Shandong Province, China.

Background The pathogenesis of congenital blepharoptosis remains controversial and most of the studies focused on the histologic changes of the levator muscle. However, thickening of the aponeurosis was reported in congenital blepharoptosis. And the thickness of the levator aponeurosis was found to be correlated with the levator function in congenital dysmyogenic blepharoptosis. Purpose The authors conducted this research to investigate the histological changes of the levator aponeurosis of simple congenital blepharoptosis patients. Patients and methods The authors analyzed 12 levator aponeurosis from ptosis patients and 21 levator aponeurosis from the cadaver specimens without relative medical history. The specimens were stained with hematoxylin and eosin as well as Sirius red. The sections were examined under light-microscopy. The content and type of collagen fibers were examined with the photos taken of the sections stained with Sirius red under polarized light-microscopy. Results The content and proportion of type I collagen increased significantly in the patient group compared with the cadaver group. The proportion of type I collagen was 97.5% in the patient group, while it was 51.5% in the cadaver group. However, no correlation was found either between the levator strength, degree of ptosis and the proportion of type I collagen in the patient group or between age, gender and proportion of type I collagen in the cadaver group. Conclusions To our knowledge, this is the first time this phenomenon was discovered. The increase of type I collagen in the levator aponeurosis of the simple congenital blepharoptosis patients may imply the increased stiffness and undermined ability of transmitting forces, dissipate energy and prevent mechanical failure in the levator aponeurosis.

Phenylalanine ammonia lyase (PAL) plays an important role in the biosynthesis of secondary metabolites regulating plant growth response. To date, the evolutionary history of the PAL family in Rosaceae plants remains unclear. In this study, we identified 16 PAL homologous genes in five Rosaceae plants (Pyrus bretschneideri, Fragaria vesca, Prunus mume, Prunus persica, and Malus × domestica). We classified these PALs into three categories based on phylogenetic analysis, and all PALs were distributed on 13 chromosomes. We tracked gene duplication events and performed sliding window analysis. These results revealed the evolution of PALs in five Rosaceae plants. We predicted the promoter of the PbPALs by PLANT CARE online software, and found that the promoter region of both PbPAL1 and PbPAL3 have at least one AC element. The results of qRT-PCR analysis found that PbPAL1 and PbPAL2 were highly expressed in the stems and roots, while expression level of PbPAL3 was relatively low in different tissues. The expression of PbPAL1 and PbPAL2 increased firstly and then decreased at different developmental periods of pear fruit. Among them, the expression of PbPAL1 reached the highest level 55 days after flowering. Three PbPALs were induced by abiotic stress to varying degrees. We transfected PbPAL1 and PbPAL2 into Arabidopsis thaliana, which resulted in an increase in lignin content and thickening of the cell walls of intervascular fibres and xylem cells. In summary, this research laid a foundation for better understanding the molecular evolution of PALs in five Rosaceae plants. Furthermore, the present study revealed the role of PbPALs in lignin synthesis, and provided basic data for regulating lignin synthesis and stone cells development in pear plants.

In this study, we investigated whether the metabolic alteration of cancer-associated fibroblasts (CAFs) occurs via miR-21 remodeling and the effect of this alteration on pancreatic cancer cells. CAFs and normal fibroblasts (NFs) were isolated and cultured. Glucose consumption and lactic acid production were tested, and lactate dehydrogenase (LDHA), pyruvate kinase m2 (PKM2), and miR-21 expression were examined. The level of glycolysis in CAFs was determined after treatment with a miR-21 inhibitor. Primary miR-21-NC CAFs and miR-21-inhibitor CAFs were indirectly co-cultured with BxPc-3 in vitro, and the invasion capacity of these cells was determined. The aerobic oxidation index of cancer cells and the expression of succinodehydrogenase (SDH) and fumarate hydratase (FH) were assessed. Compared with NFs, CAFs showed enhanced glucose uptake capacity, lactic acid production, and elevated LDHA, PKM2, and miR-21 expression. After miR-21 inhibitor treatment, the extent of glycolysis in CAFs was reduced. After indirect co-culture with CAFs, oxidative phosphorylation and SDH, FH, and MCT expression increased in BxPc-3 cells. After co-culture with miR-21-inhibitor-CAFs, oxidative phosphorylation and invasion ability of the pancreatic cancer cells decreased. MiR-21 was involved in metabolic alteration of CAFs and affected the development of cancer cells. This metabolic alteration may be an important mechanism by which the microenvironment promotes tumor progression in a nonvascular manner.

Our results not only provide a comprehensive overview of the starch biosynthetic pathway in the developing endosperm but also reveal some important protein markers that regulate the synthesis of starch. In human diets, rice (Oryza sativa L.) is an important source of starch, a substantial amount of which is accumulated in developing endosperm. A better understanding of the complicated pathways involved in starch biosynthesis is needed to improve the yield and quality of rice and other cereal crops through breeding. One pure line rice mutant, SA0419, was induced from a wild-type rice, TNG67, by sodium azide mutagenesis; therefore, TNG67 and SA0419 share the same genetic background. SA0419 is, however, a unique glutinous rice with a lower amylose content (8%) than that of TNG67 (20%), and the grains of SA0419 develop earlier and faster than those of TNG67. In this study, we used a comparative proteomic analysis to identify the differentially expressed proteins that may explain the differences in starch biosynthesis and the characteristics of TNG67 and SA0419. A gel-based proteomic approach was applied to profile the expressed proteome in the developing endosperm of these two rice varieties by nano-LC/MS/MS. Several over-expressed proteins were found in SA0419, such as plastidial ADP-glucose pyrophosphorylase (AGPase), phosphoglucomutase (PGM), pyrophosphate-fructose 6-phosphate 1-phosphotransferase (PFP), 6-phosphofructokinase (PFK), pyruvate phosphate dikinase (PPDK), starch branching enzymes (SBE) and starch debranching enzyme (SDBE), with those proteins mainly being involved in the pathways of starch metabolism and PPDK-mediated gluconeogenesis. Those over-expressed enzymes may contribute to the relatively early development, similar starch accumulation and rapid grain filling of SA0419 as compared with TNG67. This study provides a detailed biochemical description of starch biosynthesis and related information regarding a unique starch mutant that may assist future research efforts to improve the yield and quality of grain and starch in rice through breeding.

We investigated the mechanism of cancer-associated fibroblasts (CAFs) in promoting the invasion and metastasis of pancreatic cancer cells in a non-vascular manner. We verified the original generation of isolated cultured CAFs and normal fibroblasts (NFs) based on the expression of α-SMA and vimentin, and we examined the cell glycolysis level through glucose consumption and lactate production experiments. The mRNA and protein expression of CAF glycolytic enzymes, lactate dehydrogenase and pyruvate kinase m2, were examined by RT-PCR and western blotting, respectively. In vitro culture first-generation pancreatic CAFs were collected and cultured together with pancreas cancer BxPc-3 and Panc-1 cells. Cell invasion and migration were assessed using a Transwell assay and scratch test, respectively. Mitochondrial activity was assessed by experimentally determining oxidative phosphorylation (OP) activity. The aerobic oxidation index of cancer cells was also examined. Succinate dehydrogenase, fumarate hydratase (FH), and monocarboxylate transporter 1 (MCT1) expression were examined using an MCT1-specific inhibitor to remove 'tumor-stromal' metabolic coupling to observe the influence of cell interstices on pancreas cancer progression. First-generation isolated cultured CAFs and NFs both grew well, and showed active proliferation. Glucose absorption and lactate production were significantly enhanced in CAFs compared with that in NFs. PCR and western blotting showed that the lactate dehydrogenase and pyruvate kinase m2 mRNA and protein expression levels were increased in the CAFs. After indirect co-culture, OP was increased in the BxPc-3 and Panc-1 cells; correspondingly, succinate dehydrogenase, FH and MCT expression were increased. After the MCT1-specific inhibitor removed 'tumor-stromal' metabolic coupling, the migration and invasion abilities of the pancreatic cancer cells were decreased. Pancreatic CAFs can alter metabolism as well as communicate with and respond to cancer cell migration and invasion. This may be an important mechanism for promoting tumor progression in a non-vascular manner in the tumor microenvironment. The mechanism by which CAFs reshape metabolic transition requires further analysis.

The present study examined treatment pathways (the ordered sequence of medications that a patient is prescribed) for three chronic diseases (hypertension, type 2 diabetes, and depression), compared the pathways with recommendations from guidelines, discussed differences and standardization of medications in different medical institutions, explored population diversification and changes of clinical treatment, and provided clinical big data analysis-based data support for the development and study of drugs in China. In order to run the “Treatment Pathways in Chronic Disease” protocol in Chinese data sources,we have built a large data research and analysis platform for Chinese clinical medical data. Data sourced from the Clinical Data Repository (CDR) of the First Affiliated Hospital of Nanjing Medical University was extracted, transformed, and loaded into an observational medical outcomes partnership common data model (OMOP CDM) Ver. 5.0. Diagnosis and medication information for patients with hypertension, type 2 diabetes, and depression from 2005 to 2015 were extracted for observational research to obtain treatment pathways for the three diseases. The most common medications used to treat diabetes and hypertension were metformin and acarbose, respectively, at 28.5 and 20.9% as first-line medication. New drugs were emerging for depression; therefore, the favorite medication changed accordingly. Most patients with these three diseases had different treatment pathways from other patients with the same diseases. The proportions of monotherapy increased for the three diseases, especially in recent years. The recommendations presented in guidelines show some predominance. High-quality, effective guidelines incorporating domestic facts should be established to further guide medication and improve therapy at local hospitals. Medical institutions at all levels could improve the quality of medical services, and further standardize medications in the future. This research is the first application of the CDM model and OHDSI software in China, which were used to study, treatment pathways for three chronic diseases (hypertension, type 2 diabetes and depression), compare the pathways with recommendations from guidelines, discuss differences and standardization of medications in different medical institutions, demonstrate the urgent need for quality national guidelines, explores population diversification and changes of clinical treatment, and provide clinical big data analysis-based data support for the development and study of drugs in China.

In the present study, a dense granule protein 17 (gra17) and novel putative transporter (npt1) double deletion mutant of Toxoplasma gondii RH strain was engineered. The protective efficacy of vaccination using RH&Delta, gra17&Delta, npt1 tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RH&Delta, npt1 induced a strong humoral and cellular response, as indicated by the increased levels of anti-T. gondii specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-&gamma, ). Vaccinated mice were protected against a lethal challenge dose (103 tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 T. gondii Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that T. gondii RH&Delta, npt1 mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis by balancing inflammatory response with immunogenicity.

Activation of pancreatic stellate cells (PSCs) initiates pancreatic fibrosis in chronic pancreatitis and furnishes a niche that enhances the malignancy of pancreatic cancer cells (PCCs) in pancreatic ductal adenocarcinoma (PDAC). Resveratrol (RSV), a natural polyphenol, exhibits potent antioxidant and anticancer effects. However, whether and how RSV influences the biological properties of activated PSCs and the effects of these changes on tumor remain unknown. In the present study, we found that RSV impeded hydrogen peroxide-driven reactive oxygen species- (ROS-) induced activation, invasion, migration, and glycolysis of PSCs. In addition, miR-21 expression in activated PSCs was downregulated after RSV treatment, whereas the PTEN protein level increased. miR-21 silencing attenuated ROS-induced activation, invasion, migration, and glycolysis of PSCs, whereas the overexpression of miR-21 rescued the responses of PSCs treated with RSV. Moreover, RSV or N-acetyl-L-cysteine (NAC) administration or miR-21 knockdown in PSCs reduced the invasion and migration of PCCs in coculture, and the effects of RSV were partly reversed by miR-21 upregulation. Collectively, RSV inhibits PCC invasion and migration through suppression of ROS/miR-21-mediated activation and glycolysis in PSCs. Therefore, targeting miR-21-mediated glycolysis by RSV in tumor stroma may serve as a new strategy for clinical PDAC prevention or treatment.

Ophiopogon japonicus, extensively distributed in East Asia, is widely used in landscaping, the tuber of which also play a vital role in Oriental Medicine. Here, we reported the complete chloroplast...

Background The wide adoption of electronic health record systems (EHRs) in hospitals in China has made large amounts of data available for clinical research including breast cancer. Unfortunately, much of detailed clinical information is embedded in clinical narratives e.g., breast radiology reports. The American College of Radiology (ACR) has developed a Breast Imaging Reporting and Data System (BI-RADS) to standardize the clinical findings from breast radiology reports. Objectives This study aims to develop natural language processing (NLP) methods to extract BI-RADS findings from breast ultrasound reports in Chinese, thus to support clinical operation and breast cancer research in China. Methods We developed and compared three different types of NLP approaches, including a rule-based method, a traditional machine learning-based method using the Conditional Random Fields (CRF) algorithm, and deep learning-based approaches, to extract all BI-RADS finding categories from breast ultrasound reports in Chinese. Results Using a manually annotated dataset containing 540 reports, our evaluation shows that the deep learning-based method achieved the best F1-score of 0.904, when compared with rule-based and CRF-based approaches (0.848 and 0.881 respectively). Conclusions This is the first study that applies deep learning technologies to BI-RADS findings extraction in Chinese breast ultrasound reports, demonstrating its potential on enabling international collaborations on breast cancer research.

Bladder reconstruction remains challenging for urological surgery due to lack of suitable regenerative scaffolds. In a previous study, we had used a collagen-binding basic fibroblast growth factor (CBD-bFGF) to bind bFGF to the collagen scaffold, which could promote bladder regeneration in rats. However, the limited graft size in rodent models cannot provide enough evidence to demonstrate the repair capabilities of this method for severely damaged bladders in humans or large animals. In this study, the CBD-bFGF was used to activate a bladder acellular matrix (BAM) scaffold, and the CBD-bFGF/BAM functional scaffold was assessed in a canine model with a large segment defect (half of the entire bladder was resected). The results demonstrated that the functional biomaterials could promote bladder smooth muscle, vascular, and nerve regeneration and improve the function of neobladders. Thus, the CBD-bFGF/BAM functional scaffold may be a promising biomaterial for bladder reconstruction.

Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined. Transwell chambers were used to examine tumor invasiveness, and scratch assays were performed to examine cell migration. Reverse transcription-polymerase chain reaction and western blot analysis were used to quantitate the mRNA and protein expression of E-cadherin, vimentin, Snail and hypoxia-inducible factor (HIF)-1α. BxPc-3 and Panc-1 cells grown under hypoxic conditions demonstrated increased partial EMT, reduced E-cadherin expression, and increased vimentin expression, compared with cells grown under normoxic or hyperoxic conditions. Cells grown under hypoxic conditions also indicated increased migration and invasiveness. HIF-1α mRNA and protein expression was increased in cells grown under hypoxic conditions. These changes were reversed when a specific inhibitor of the HIF-1α receptor was used to block HIF-1α signaling. Differences in oxygen concentration at primary sites and homing sites are important in the EMT-MET process, and the underlying mechanism may involve HIF-1α-Snail signaling.

Background: This study aimed to investigate the prevalence and risk factors for hypertension, diabetes, and dyslipidemia, and to evaluate their additive effects on myocardial infarction (MI) and stroke in Nanjing in East China. Methods: A multistage, stratified random cluster sampling method was used to select representative participants. All eligible participants completed questionnaires, physical measurements, and blood tests. Multivariable and univariable logistic regression analyses were used to identify associated risk factors and evaluate additive effects on cardiovascular events, respectively. Results: Hypertension was the most prevalent chronic disease among 11,036 participants enrolled (18.5%), followed by dyslipidemia (8.3%) and diabetes (6.0%). The prevalence of hypertension was higher in men than in women while no sex-related difference was observed in the prevalence of diabetes and dyslipidemia. Older age and higher body mass index were risk factors for all three diseases. Sex, central obesity, smoking, number of family members, salt intake, and family history of hypertension were associated with hypertension; central obesity, smoking, alcohol assumption, and family history of diabetes correlated with diabetes; and female sex, higher education, and alcohol assumption were risk factors for dyslipidemia. Hypertension complicated with dyslipidemia conferred more risk of MI and stroke than independent effects. Diabetes also contributed to risk based on hypertension or dyslipidemia. Conclusions: The burden of hypertension and diabetes has stopped increasing. However, total cholesterol (TC) concentration in the population has not been well controlled. A more comprehensive approach to managing dyslipidemia, hypertension, and diabetes needs to be developed, especially for individuals with multiple cardiovascular risk factors.

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)-MET (mesenchymal-epithelial transition) two-step process. In this study, we investigated the importance of cancer associated fibroblasts (CAF) in the process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were identified and verified via the expression of α-SMA and vimentin. Using an indirect three-dimensional co-culture model, the morphological changes were observed by light microscopy and laser scanning confocal microscopy. The invasive and migration capacity of pancreatic cancer cells was determined by Transwell chamber migration assay or scratch assay. The mRNA and protein expression levels of E-cadherin, vimentin, and Gli1 were determined by RT-PCR and western blotting. Primary cultures of isolated CAF, NF, HSF showed satisfactory growth with active proliferation. Indirect co-culture with CAF, BxPc-3 and Panc-1 cells showed significant partial EMT, reduced E-cadherin expression, and enhanced vimentin expression as compared with the single culture and NF/HSF co-culture groups, with corresponding increases in migratory and invasive capacities. PCR and western blotting results showed that mRNA and protein expression levels of Gli1 in CAF and Snail in cancer cells were increased. This process could be reversed by inhibition of hedgehog (HH) signaling in CAF. In the tumor microenvironment, activation of CAF is the key event in mediating partial EMT, and its mechanism may be associated with paracrine action after activation of HH signaling in CAF.

Nrf2 (NF-E2-related factor 2) pathway and autophagy both can respond to oxidative stress to promote cancer cells to survive in the tumor microenvironment. We, therefore, explored the relevance between Nrf2 pathway and autophagy in pancreatic cancer cells upon stimulation of reactive oxygen species (ROS). Pancreatic cancer cells were cultured under controlled ROS stressing condition or basal condition. Different inhibitors were used to prevent autophagy at particular stages. Nrf2 siRNA was used to inhibit Nrf2 pathway activation. Ad-mRFP-GFP-LC3 infection was used to monitor autophagic flux. The result shows that a small amount of exogenous hydrogen peroxide (H2O2) can significantly improve the level of intracellular ROS. Moreover, our findings indicate that ROS promotes the activation of both Nrf2 pathway and autophagy in pancreatic cancer cells. Moreover, our data demonstrate that suppression of autophagic activity at particular stages results in an increased promotion of Nrf2 pathway activation upon ROS stimulation. Furthermore, we found that silencing of Nrf2 promotes autophagy upon ROS stimulation. In addition, Nrf2 interference effectively promotes autophagic flux upon ROS stimulation. In summary, our findings suggest that Nrf2 pathway and autophagy have a negative interaction with each other upon ROS stimulation.

Lipoxin A4(LXA4), an endogenous arachidonic acid metabolite, was previously considered an anti-inflammatory lipid mediator. But it also has the potential to inhibit cancer progression. To explore the therapeutic effect of LXA4in pancreatic cancer, we used Panc-1 cells to investigate the mechanism by which LXA4can attenuate pancreatic cancer cell invasion. Our data showed that LXA4significantly inhibited both cell invasion and the expression of matrix metalloproteinase- (MMP-) 9 and MMP-2. Further experiments implied that LXA4decreased the levels of intracellular reactive oxygen species (ROS) and the activity of the extracellular signal regulated kinases (ERK) pathway to achieve similar outcome to ROS scavenger N-acetyl-L-cysteine (NAC). However, a decreased level of intracellular ROS was not observed in cells treated with the specific ERK pathway inhibitor FR180204. The blocking of either intracellular ROS or ERK pathway caused the downregulation of MMP-9 and MMP-2 expression. Furthermore, tests revealed that LXA4inhibited MMP-9 and MMP-2 at the mRNA, protein, and functional levels. Finally, LXA4dramatically limited the invasion of CoCl2-mimic hypoxic cells and abrogated intracellular ROS levels, ERK activity, and MMPs expression. These results suggest that LXA4attenuates cell invasion in pancreatic cancer by suppressing the ROS/ERK/MMPs pathway, which may be beneficial for preventing the invasion of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy.

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts., A survey of 419,680 peer-reviewed papers in 16 languages reveals that non-English-language studies can expand geographical (by 12-25%) and taxonomic (by 5-32%) coverage of English-language evidence on the effectiveness of biodiversity conservation interventions, especially in biodiverse regions.