Deep Learning-Based Classification of Hepatocellular Nodular Lesions on Whole-Slide Histopathologic Images.

BACKGROUND & AIMS: Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS: The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS: We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS: We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.

Capillary-in-Capillary Electrospray Ionization (CC-ESI) Source Enabling Convenient Sampling and Quantitative Analysis for Point-of-Care Testing.

With outstanding analytical performances, mass spectrometry (MS) has shown great potential for clinical applications. To facilitate the sampling process and quantitative analysis, a capillary-in-capillary electrospray ionization (CC-ESI) source was developed in this study. Utilizing two nested capillaries as a sampler and an ESI emitter, the source enabled spontaneous liquid sampling based on the capillary phenomenon and electrospray ionization mass spectrometry (ESI-MS) analysis. Apart from the cheap price, high portability, and disposability, the CC-ESI had merits of quantitation capability as well as adequate sensitivity. By coupling CC-ESI to a miniature mass spectrometer (mini-MS), a limit of detection (LOD) of 1 ng/mL was achieved for standard imatinib at collision-induced dissociation (CID) tandem MS mode, and a LOQ of 1 ng/mL was obtained for atenolol and imatinib (with isotopic internal standard) at multiple ion reaction monitoring (MRM) modes. As two demonstrations for analysis of practical samples, rapid analysis of abused drugs on surface and quantitative analysis of therapeutic drugs in whole blood were also performed with a CC-ESI mini-MS.

Construction of the first high-density genetic linkage map and QTL mapping of flavonoid and leaf-size related traits in Epimedium.

BACKGROUND: Leaves are the main medicinal organ in Epimedium herbs, and leaf flavonoid content is an important criterion of Epimedium herbs. However, the underlying genes that regulate leaf size and flavonoid content are unclear, which limits the use of breeding for Epimedium development. This study focuses on QTL mapping of flavonoid and leaf-size related traits in Epimedium. RESULTS: We constructed the first high-density genetic map (HDGM) using 109 F1 hybrids of Epimedium leptorrhizum and Epimedium sagittatum over three years (2019-2021). Using 5,271 single nucleotide polymorphism (SNP) markers, an HDGM with an overall distance of 2,366.07 cM and a mean gap of 0.612 cM was generated by utilizing genotyping by sequencing (GBS) technology. Every year for three years, 46 stable quantitative trait loci (QTLs) for leaf size and flavonoid contents were discovered, including 31 stable loci for Epimedin C (EC), one stable locus for total flavone content (TFC), 12 stable loci for leaf length (LL), and two stable loci for leaf area (LA). For flavonoid content and leaf size, the phenotypic variance explained for these loci varied between 4.00 and 16.80% and 14.95 and 17.34%, respectively. CONCLUSIONS: Forty-six stable QTLs for leaf size and flavonoid content traits were repeatedly detected over three years. The HDGM and stable QTLs are laying the basis for breeding and gene investigation in Epimedium and will contribute to accelerating the identification of desirable genotypes for Epimedium breeding.

Phenotype correlation analysis and excellent germplasm screening of herb Bletilla Rchb. f. based on comprehensive evaluation from thirty-three geographic populations.

BACKGROUND: The Bletilla genus of Orchidaceae includes plants with great economic value, among which B. striata is the main traditional medicinal plant, and its pseudobulb, known as BaiJi, was first recorded in Shennong's Classic of Materia Medica. However, there has been little systemic evaluation of the germplasm quality of Bletilla plants in China. In order to comprehensive evaluate the Bletilla resources in China and screen out the candidate phenotypic traits determining yield and/or quality of Bletilla, the variation of phenotypic indicators (pseudobulb, leaf, stem, inflorescence, flower) and active ingredients contents (polysaccharide, total phenolics and militarine) in different populations of B. striata and B. ochracea were investigated through 4 years' common-garden experiment. RESULTS: There were abundant phenotypic variations and significant differences among different populations in the morphological phenotypes, pseudobulb weight and main active ingredient contents. AHBZ, HBLT and HBSN populations showed good prospects for industrial development, presenting higher quality in terms of yield and main active ingredient content. Pseudobulb yield, polysaccharide and total phenol content are positively correlated with phenotypic traits. Militarine content is negatively correlated with almost all indexes. Plant height, leaf width and stem diameter may be important indicators of potential excellent germplasms. CONCLUSIONS: Bletilla is not strictly geoauthentic medicinal plants. B. ochracea could be accepted as an alternative resource to B. striata. The best harvest period of Bletilla is the third year after cultivation. Plant height, leaf width and stem diameter may be important indicators of potential excellent germplasms. These results provide important information required for the efficient screening and utilization of Bletilla germplasm resources.

Development of SSR and SNP markers for identifying opium poppy.

Papaver somniferum L. (opium poppy) is the original plant of heroin, which is a major narcotic drug, and this plant has brought great harm to human health. However, the ban on opium poppy cultivation and trafficking is facing great challenges because of abnormal profits. Therefore, rapid and accurate identification is important to address the abovementioned problems. In this study, eleven simple sequence repeats (SSR) markers and two single nucleotide polymorphism (SNP) markers were mined to distinguish opium poppy from other six Papaver species. These molecular markers were further verified through a large number of plant materials of these seven Papaver species. An excellent multiplex polymerase chain reaction (PCR) system that simultaneously amplifies the three of eleven SSR markers was developed, which effectively improves the efficiency and speed of identification. The present research is of great implication for identifying and investigating the illegal cultivation and trafficking of opium poppy.

Multistimuli-Responsive Materials Based on Zn(II)-Viologen Coordination Polymers and Their Applications in Inkless Print and Anticounterfeiting.

Recently, stimuli-responsive materials have attracted great attention, while most of them respond to single or two stimuli. Thus, it is essential to design multifunctional stimuli-responsive materials and develop their applications. The strategy that constructing high-dimensional coordination polymers facilitates the application scope of a viologen-based photochromic system is put forward and confirmed for the first time. Herein, a novel multistimuli-responsive viologen-based Zn-MOF with a two-dimensional framework has been successfully designed and synthesized. Complex 1 exhibits chromic behavior under a variety of external stimuli such as 365 nm UV, X-rays, heat, electricity, and ethylamine. More interestingly, the crystal state of complex 1 displays dual fluorescence and room-temperature phosphorescence (RTP) emission and emits a yellow afterglow when turning off the UV lamp. In addition, Eu(III)-functionalized hybrids, Eu3+@Zn-MOF, were prepared by coordinated postsynthetic modification based on viologen complexes for the first time. The sample of Eu3+@Zn-MOF inherits the photochromic characteristics of the viologen complexes and gives the distinctive fluorescence of the europium ions. Based on the multicolor switching of 1 and Eu3+@Zn-MOF, their possible practical utilization was successfully developed in the fields of inkless, erasable print media, electrochromic information tag printing, information encryption, and anticounterfeiting.

Solvent-Modulated Self-Assembly of Naphthalenediimide-Based Cd(II) Complexes and the Controllable Photochromism via Conformational Isomerization.

Rational regulation of the properties of photochromic materials is a challenging and meaningful work. In the present work, NDI-based complexes, namely, [Cd0.5(NDI)(HBDC)]·H2O (1) and a series of conformational isomers of {[Cd(NDI)0.5(BDC)]·MeCN}n (2), were synthesized by varying the solvent conditions (H2BDC = terephthalic acid, NDI = N,N'-bis(3-pyridylcarbonylhydrazine)-1,4,5,8-naphthalene diimide). Complex 1 exhibits a 0D mononuclear structure without photochromic behavior due to the bad conjugation of the naphthalene diimide moiety. The conformational isomers of complex 2 manifest a 3D network, showing ultra-fast photo-induced intermolecular electron transfer photochromic behavior under X-ray, UV, and visible light. However, they show different photochromic rates and coloring contrast upon photoirradiation, which originates from their difference in the distances of lone pair(COO)···π(NDI). This was realized via controlling the solvent ratio in the reaction system. In addition, compared to UV/X-ray light, 2 exhibits greater sensitivity to visible light and is an organic-inorganic hybrid material with photomodulated luminescence. Based on the excellent performance, complex 2 can be applied to filter paper, showing potential applications as an inkless printing medium and selective perception of ammonia and amine vapors in the solid state via different visual color changes.

Differential diagnosis of Crohn's disease and intestinal tuberculosis: development and assessment of a nomogram prediction model.

BACKGROUND: China is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn's disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model. METHODS: A total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve. RESULTS: T-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits. CONCLUSION: A nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.

Neuroendocrine-Immune Regulatory Network of Eucommia ulmoides Oliver.

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.

[Review of classical prescriptions in treatment of ulcerative colitis].

Ulcerative colitis(UC) is a continuous inflammatory bowel disease with the main clinical manifestations of abdominal pain, diarrhea, and mucous bloody stools, mainly attacking the colorectal mucosa and submucosa. It is characterized by high recurrence rate, difficult cure, and clustering and regional occurrence. Chinese medicinal prescriptions for the treatment of UC have good therapeutic effect, multi-target regulation, slight toxicity, and no obvious side effects. In particular, the classical prescriptions highlight the characteristics and advantages of traditional Chinese medicine theory and have attracted much attention in recent years. To enable researchers to timely and comprehensively understand the classical prescriptions in the treatment of UC, we reviewed the studies about the pharmacodynamic material basis, quality control, action mechanism, and clinical application of relevant classical prescriptions. We first introduced the latest research progress in the active components such as alkaloids, polysaccharides, saponins, and flavonoids in relevant classical prescriptions. Then, we reviewed the latest research achievements on the quality control of classical prescriptions for the treatment of UC by gas chromatography, liquid chromatography, mass spectrometry, liquid chromatography-mass spectrometry and the like. Further, we summarized the research advances in the mechanisms of relevant prescriptions in the treatment of UC based on network pharmacology, molecular docking, integrated pharmacology platform, and animal experiments. Finally, we generalized the clinical application of the classical prescriptions for clearing heat and removing dampness, mildly regulating cold and heat, soothing liver and regulating spleen, strengthening spleen and invigorating Qi, and tonifying spleen and stomach. By systematic summary of the research progress in relevant classical prescriptions, we hope to promote the application and development of such prescriptions in UC treatment.

Multistimuli Responsive Solid-State Emission of a Zinc(II) Complex with Multicolour Switching.

The development of smart luminescent materials, especially those stimulus-responsive fluorescent materials that can switch between different colors repeatedly under external stimulation based on a single molecule, is of great significance but a challenge. In this work, a novel zinc(II)-Schiff base complex (ZnL2) was obtained and characterized. Upon exposure to the HCl and NH3 vapors, it displayed remarkable tricolor acidochromic behavior with high contrast and rapid response under the ambient light as well as UV light (365 nm). The XPS analyses of ZnL2 crystals before and after HCl/NH3 fuming show that the acidochromism originates principally from the adsorption of vapor and the gas-solid reaction equilibrium on the crystal surface. The reddish-brown color of the HCl-fumigated ZnL2 crystals could be attributed to the generation of HL at the surface of ZnL2, and red-shifted emission could be ascribed to the self-absorption effect. The single crystal X-ray diffraction data indicate that these processes cause slight changes in the molecular conformation and crystal packing. ZnL2 shows reversible mechanochromic luminescence behavior between yellow and orange emission during the grinding-fuming/heating cycles due to the modulation between amorphous and crystalline states. Moreover, ZnL2 was successfully made into test paper for the rapid detection of HCl/NH3 vapors and mechanical stimuli.

A Multistimuli Responsive Crystalline Cd(II)-Viologen Coordination Polymer with Single-Crystal-Single-Crystal Transformation.

It is necessary to develop stable and fast multistimuli responsive materials due to the growing demand in our daily life. In this work, a new viologen-based Cd-complex (1) exhibits multiple thermochromic and photochromic behaviors through 10 states with 7 colors. For example, it responds to both Cu Kα/Mo Kα X-ray sources and UV dual light quickly with a color change from colorless to dark blue (1X) (Cu Kα/Mo Kα X-ray sources) and cyan (1-UV) (UV light), respectively. Interestingly, it exhibits a three-step coloration phenomenon when heated, which is unprecedented in viologen compounds. Crystal 1 undergoes a color change to pink, blue, and brown under 130, 180, and 240 °C, respectively. In addition, upon fumigation, both 1P and 1Q undergo a decoloration process to colorless (1K) and yellow (1T), respectively. Four more states (1P, 1K, 1T, and 1O) obtained via dehydration-hydration treatment are all photochromic. More importantly, via single-crystal-single-crystal transformation (SC-SC), the photochromic and thermochromic behaviors of 1 were investigated from the molecular level, which is also rather rare for thermochromic species. The detailed electron donor and the pathways for electron transfer were clearly given according to the results of crystal structure. The colorful states upon external stimuli may be attributed to the multiple pathways for electron transfer.

Multistimulus Response of Two Tautomeric Zn(II) Complexes and Their White-Light Emission Based on Different Mechanisms.

A triphenylamine (TPA)-based 2H-quinazoline Zn(II) complex (Q-TPA-Zn) exhibiting dual fluorescence and phosphorescence emission in the solid state was designed and prepared. It possesses mechanochromic luminescence and thermochromic luminescence properties. In the solid state, the white afterglow luminescence could be observed at 77 K (CIExy: 0.27, 0.33) while cyan luminescence could be observed at 297 K. After thermolysis at 300 °C, Q-TPA-Zn could be transformed into Schiff base complex S-TPA-Zn with white fluorescence in the powder state (CIExy: 0.32, 0.38), in methanol (CIExy: 0.32, 0.39), and in dimethylformamide (CIExy: 0.26, 0.32) at room temperature. This arises from dual emission of normal* emission and tautomeric* emission induced by excited-state intramolecular proton transfer (ESIPT) from the benzimidazole NH group to the Schiff base N atom. Q-TPA-Zn could also be transformed into its isomeric form, S-TPA-Zn, through photochemical ring-opening reaction upon irradiation under 365 nm in the solution, exhibiting high-contrast photochromic luminescence. Interestingly, S-TPA-Zn could further be transformed into its zwitterionic isomer after continuous irradiation. The same ring-opening reaction could also take place for the orgainc compound Q-TPA via heating or 365 nm irradiation. The ring-opening reaction mechanism and ESIPT emission were interpreted via theoretical calculation.

Antibacterial Activity and Mechanism of Linalool against Shewanella putrefaciens.

The demand for reduced chemical preservative usage is currently growing, and natural preservatives are being developed to protect seafood. With its excellent antibacterial properties, linalool has been utilized widely in industries. However, its antibacterial mechanisms remain poorly studied. Here, untargeted metabolomics was applied to explore the mechanism of Shewanella putrefaciens cells treated with linalool. Results showed that linalool exhibited remarkable antibacterial activity against S. putrefaciens, with 1.5 µL/mL minimum inhibitory concentration (MIC). The growth of S. putrefaciens was suppressed completely at 1/2 MIC and 1 MIC levels. Linalool treatment reduced the membrane potential (MP); caused the leakage of alkaline phosphatase (AKP); and released the DNA, RNA, and proteins of S. putrefaciens, thus destroying the cell structure and expelling the cytoplasmic content. A total of 170 differential metabolites (DMs) were screened using metabolomics analysis, among which 81 species were upregulated and 89 species were downregulated after linalool treatment. These DMs are closely related to the tricarboxylic acid (TCA) cycle, glycolysis, amino acid metabolism, pantothenate and CoA biosynthesis, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. In addition, linalool substantially affected the activity of key enzymes, such as succinate dehydrogenase (SDH), pyruvate kinase (PK), ATPase, and respiratory chain dehydrogenase. The results provided some insights into the antibacterial mechanism of linalool against S. putrefaciens and are important for the development and application of linalool in seafood preservation.

Post-contrast 3D-FLAIR in idiopathic sudden sensorineural hearing loss.

PURPOSE: Our study investigated correlations between clinical characteristics, particularly hearing recovery, interval time between onset and three-dimensional fluid attenuation inversion recovery magnetic resonance imaging (3D-FLAIR MRI), and the signal intensity of post-contrast 3D-FLAIR MRI in patients with idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: The study enrolled 100 SSNHL patients. The signal intensities and asymmetry ratios of the inner ear structures, including the cochleae, vestibules and vestibulocochlear nerve, were evaluated and calculated. The relationships between the clinical characteristics and MRI findings were assessed. RESULTS: After intravenous gadolinium (Gd) injection, 3D-FLAIR revealed high signal intensities in 65 patients. The corrected asymmetry ratios of cochlea correlated closely with interval time between onset and MRI. The asymmetry ratios of the inner ear structures were significantly lower in patients with final complete to partial hearing recovery. The corrected asymmetry ratios of the inner ear structures correlated with initial/final pure tone audiometry (PTA) and hearing recovery in the affected ear. Notably, it was shown that the corrected asymmetry ratios identified a poor prognosis for hearing recovery, with a sensitivity and specificity of 67.9% and 75.0% in the cochlea, 83.3% and 75.0% in the vestibule, and 52.4% and 81.2% in the vestibulocochlear nerve, respectively. CONCLUSIONS: Post-contrast 3D-FLAIR after intravenous Gd injection in SSNHL can be used to assess the permeability of the blood-labyrinth and blood-nerve barriers. The asymmetry ratios of the inner ear structures may identify patients with poor prognosis for hearing recovery. Signal characteristics are closely related to interval time between onset and MRI.

Preservation of Denonvilliers' fascia for nerve-sparing laparoscopic total mesorectal excision: A neuro-histological study.

Urogenital complications due to pelvic autonomic nerve damage frequently occur following rectal surgery. We investigated whether total mesorectal excision (TME) with preservation of the Denonvilliers' fascia (DVF) can effectively prevent the removal of pelvic autonomic nerves through microscopy. Twenty consecutive male patients with mid-low rectal cancer who received TME with preservation or resection of the Denonvilliers' fascia (P and R groups, respectively) were included. Serial transverse sections from surgical specimens were studied histologically. Nerve fibers at the surfaces of the mesorectum were counted. Clinical correlation between the amount of nerve fibers removed and post-operative sexual function was analyzed. Nerve fibers closely localized to the DVF in the R group displaying rich erectile activity (positive anti-nNOS immunostaining). At the anterior surface of the mesorectum, the mean numbers of nNOS-positive nerve fibers per specimen in the P group were significantly lower than the R group (3.0 ± 1.8 vs. 5.0 ± 2.3, P < 0.05). Compared to the R group, patients in the P group had higher IIEF scores and better erectile function at 3 and 6 months post-operatively. The DVF is a key risk zone for pelvic denervation during laparoscopic TME. Preservation of the DVF can prevent the removal of autonomic nerves and protect post-operative erectile function. Clin. Anat. 32:439-445, 2019. © 2019 Wiley Periodicals, Inc.

Collapsin response mediator protein 4 promotor methylation level as a potential predictor for diagnosing primary malignant lymphoma of the prostate.

BACKGROUND: Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. METHODS: We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (-) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. RESULTS: The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (-) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal-Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P < 0.001). An ROC curve analysis found that CRMP4 methylation > 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. CONCLUSIONS: Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

A study on the roles of Helicobacter pylori in bile reflux gastritis and gastric cancer.

PURPOSE: To observe the infection rates of Helicobacter pylori (HP) in bile reflux gastritis (BRG) and gastric cancer and the clinical significance of HP eradication in BRG and gastric cancer patients complicated with HP. METHODS: 248 patients diagnosed with BRG and gastric cancer via gastroscopy were enrolled in this study. HP detection and infection rates of HP were evaluated. Then, BRG and gastric cancer patients complicated with HP were randomly divided into BRG group 1, BRG group 2, gastric cancer group 1 and gastric cancer group 2. BRG group 1 and gastric cancer group 1 were treated with conventional anti-inflammatory drugs for 10 days, and BRG group 2 and gastric cancer group 2 were treated with anti-HP drugs in addition to conventional anti-inflammatory drugs. One month after drug withdrawal, the infection rates of HP in each group were evaluated, and prognostic follow-up was performed to record the post-therapy patient conditions. RESULTS: HP infection rate was 35.8% (57/159) in the BRG group and 73.0% (65/89) in the gastric cancer group, with statistically significant difference (p<0.01). In patients treated with anti-HP drugs had the HP infection rate effectively reduced. The treatment effective rates of patients with BRG and gastric cancer complicated with HP infection after eradication of HP were 82.8 and 68.8%, respectively, while those of patients with non-eradicated HP were only 46.4 and 37.5 %, respectively. The differences between the two groups were statistically significant (p<0.05). CONCLUSION: HP is directly and closely related to the occurrence of gastric diseases, HP infection rate in patients with gastric cancer is significantly higher than that in patients with BRG, and the treatment of HP can effectively improve the rehabilitation rate in patients with gastric diseases.

[Current situation and prospect of resource evaluation and sustainable utilization on Bletilla].

The plants of Bletilla are one of the groups in Orchidaceae with the highest economic value. As the traditional Chinese medicinal material, Bletillae Rhizoma exhibits excellent efficacy in hemostatic, antibiosis, detumescent, anticancer activities and regenerating tissue to heal wound, which has great development potential. However, Bletillae Rhizoma is mainly collected from wild resources. At present, the quantity of wild resources of Bletilla plants has sharply decreased and is far from meeting the needs. Resource appraisal and breeding and cultivation of excellent germplasms of Bletilla plants are important for scientific utilization of the resources of the genus. This paper reviewed the following researches of Chinese Bletilla resources: species and distribution, genetic diversity, active ingredient evaluation, breeding, as well as seeding production and cultivation techniques. Suggestions were also provided in further researches on the resources evaluation, sustainable development and efficient utilization of Chinese Bletilla plants.

A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers.

It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6.785, 4.071, 1.357 mg·kg-1·d-1, respectively) of GQD extract for 60 d. Metformin (300 mg·kg-1·d-1) was taken as the positive control. Blood samples were collected to assess serum biochemical indexes and metabolic profiling. After "Focus" analysis, the biochemical index triglycerides (TG) and insulin sensitivity (ISI) were identified as focused integrated biomarkers (FIBs), while arachidonic acid and docosatetraenoic acid were the metabolic FIBs. Dose-effect relationship curves of GQD were built based on these types of FIBs. Furthermore, the two dose-effect relationship curves showed similar trends with the middle dosage displaying the greatest efficacy, suggesting that insulin function and arachidonic acid metabolism played important roles in 2-DM and the responses to GQD. The metabolic FIB docosatetraenoic should be further explored for understanding its involvement in the process of 2-DM occurrence and the treatment. This "Focus" mode provides a novel strategy to evaluate the dose-effect relationship of a TCM. The system and concepts established here may also be applicable for assessing the dose-effect relationships of Western medicines.