Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

Identification of osteoarthritis-characteristic genes and immunological micro-environment features through bioinformatics and machine learning-based approaches.

BACKGROUND: Osteoarthritis (OA) is a multifaceted chronic joint disease characterized by complex mechanisms. It has a detrimental impact on the quality of life for individuals in the middle-aged and elderly population while also imposing a significant socioeconomic burden. At present, there remains a lack of comprehensive understanding regarding the pathophysiology of OA. The objective of this study was to examine the genes, functional pathways, and immune infiltration characteristics associated with the development and advancement of OA. METHODS: The Gene Expression Omnibus (GEO) database was utilized to acquire gene expression profiles. The R software was employed to conduct the screening of differentially expressed genes (DEGs) and perform enrichment analysis on these genes. The OA-characteristic genes were identified using the Weighted Gene Co-expression Network Analysis (WGCNA) and the Lasso algorithm. In addition, the infiltration levels of immune cells in cartilage were assessed using single-sample gene set enrichment analysis (ssGSEA). Subsequently, a correlation analysis was conducted to examine the relationship between immune cells and the OA-characteristic genes. RESULTS: A total of 80 DEGs were identified. As determined by functional enrichment, these DEGs were associated with chondrocyte metabolism, apoptosis, and inflammation. Three OA-characteristic genes were identified using WGCNA and the lasso algorithm, and their expression levels were then validated using the verification set. Finally, the analysis of immune cell infiltration revealed that T cells and B cells were primarily associated with OA. In addition, Tspan2, HtrA1 demonstrated a correlation with some of the infiltrating immune cells. CONCLUSIONS: The findings of an extensive bioinformatics analysis revealed that OA is correlated with a variety of distinct genes, functional pathways, and processes involving immune cell infiltration. The present study has successfully identified characteristic genes and functional pathways that hold potential as biomarkers for guiding drug treatment and facilitating molecular-level research on OA.

Optimal fibular tunnel direction for anterior talofibular ligament reconstruction: 45 degrees outperforms 30 and 60 degrees.

PURPOSE: There is currently no consensus on the optimal drilling direction of the fibular bone tunnel for anterior talofibular ligament (ATFL) reconstruction, and few studies have investigated the potential injury to the peroneus longus and brevis tendons and the possibility of fibular fractures during the drilling process. The aim of this study was to assess the potential risk of drilling the tunnel from different directions and determine the most appropriate tunnel direction. The hypothesis was that drilling the tunnel in the 45-degree direction would be the safest and most suitable for the fibular tunnel. METHODS: Forty-eight fibular tunnels were drilled on fresh ankle specimens using a K-wire guide and a 5.0 mm hollow drill. Three tunnel orientations were created, parallel to the sagittal plane of the long axis of the fibula and angled 30°, 45°, and 60° to the coronal plane. The length of the fibular tunnel and the distances from the outlet of the K-wire to the peroneus longus and brevis tendons were measured. The occurrence of a fibula fracture was also observed. RESULTS: The lengths of the bone tunnels in the three groups were 32.9 ± 6.1 mm (30°), 27.2 ± 4.4 mm (45°) and 23.6 ± 4.0 mm (60°). The length of the tunnel drilled at 30° was the longest when compared with that of the tunnels drilled at 45° and 60° (all p values < 0.05). The distances from the outlet of the K-wire to the peroneus longus tendon were 3.0 ± 3.8 mm (30°), 3.8 ± 3.2 mm (45°) and 5.3 ± 1.8 mm (60°), and the distances to the peroneus brevis tendon were 4.2 ± 4.0 mm (30°), 6.1 ± 3.8 mm (45°), 7.9 ± 3.5 mm (60°). In terms of protecting the peroneus longus and brevis tendons, drilling in the 60° direction was better than drilling in the 30° and 45° directions (all p values < 0.05). The risk of injury to the peroneal longus and brevis tendons was 62.5% (30°), 31.3% (45°), and 0% (60°). Although no fibular fractures were observed in any of the three directions, drilling the bone tunnel in the 60° direction disrupted the lateral cortex of the fibula. CONCLUSION: This study shows that drilling the tunnel in the 45° direction is less likely to cause injury to the peroneus longus and brevis tendons, while ensuring that the tunnel has a sufficient length and avoiding fracturing the distal fibula. Drilling a fibular bone tunnel in a 45° direction is safer and recommended for ATFL reconstruction.

Impact of early heparin therapy on mortality in critically ill patients with sepsis associated acute kidney injury: a retrospective study from the MIMIC-IV database.

Background: Inflammatory-coagulation dysfunction plays an increasingly important role in sepsis associated acute kidney injury (SAKI). This study aimed to investigate whether early heparin therapy improves survival in patients with SAKI. Methods: Patients with SAKI were identified from the Medical Information Mart for Intensive Care-IV database. The patients were divided into two groups: those who received heparin subcutaneously within 48 h after intensive care unit (ICU) admission and the control group, who received no heparin. The primary endpoint was ICU mortality, the secondary outcomes were 7-day, 14-day, 28-day, and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), and E-value analyses were performed. Results: The study included 5623 individuals with SAKI, 2410 of whom received heparin and 3213 of whom did not. There were significant effects on ICU and 28-day mortality in the overall population with PSM. MSCM further reinforces the efficacy of heparin administration reduces ICU mortality in the general population. Stratification analysis with MSCM showed that heparin administration was associated with decreased ICU mortality at various AKI stages. Heparin use was also associated with reduced 28-day mortality in patients with only female, age >60 years, and AKI stage 3, with HRs of 0.79, 0.77, and 0.60, respectively (p < 0.05). E-value analysis suggests robustness to unmeasured confounding. Conclusion: Early heparin therapy for patients with SAKI decreased ICU mortality. Further analysis demonstrated that heparin therapy was associated with reduced 28-day mortality rate in patients only among female, age > 60 years and AKI stage 3.

Deployment Optimization Method of Multistatic Radar for Constructing Circular Barrier Coverage.

To construct circular barrier coverage (CBC) with multistatic radars, a deployment optimization method based on equipartition strategy is proposed in this paper. In the method, the whole circular area is divided into several sub-circles with equal width, and each sub-circle is blanketed by a sub-CBC that is built based on the multistatic radar deployment patterns. To determine the optimal deployment patterns for each sub-CBC, the optimization conditions are firstly studied. Then, to optimize the deployment of the whole circular area, a model based on minimum deployment cost is proposed, and the proposed model is divided into two sub-models to solve the optimization issue. In the inner model, it is assumed that the width of a sub-circle is given. Based on the optimization conditions of the deployment pattern, integer linear programming (ILP) and exhaustive method (EM) are jointly adopted to determine the types and numbers of deployment patterns. Moreover, a modified formula is introduced to calculate the maximum valid number of receivers in a pattern, thus narrowing the search scope of the EM. In the outer model, the width of a sub-circle is assumed to be a variable, and the EM is adopted to determine the minimum total deployment cost and the optimal deployment patterns on each sub-circle. Moreover, the improved formula is exploited to determine the range of width for a sub-circle barrier and reduce the search scope of the EM. Finally, simulations are conducted in different conditions to verify the effectiveness of the proposed method. The simulation results indicate that the proposed method can spend less deployment cost and deploy fewer transmitters than the state-of-the-artwork.

Review and Thinking on Forensic Pathological Changes of Coronavirus-Infected Diseases / 法医学杂志

Since the beginning of this century, three types of coronavirus have widely transmitted and caused severe diseases and deaths, which strongly indicates that severe infectious diseases caused by coronavirus infection are not accidental events. Coronavirus-infected diseases are mainly manifested by respiratory symptoms, with multiple organ dysfunctions. Precisely investigating the pathological process, characteristics and pathogenesis of coronavirus-infected diseases will be beneficial for us to understand clinical manifestations and provide targeted suggestions on prophylaxis and treatment. This paper briefly reviews the pathological findings of three known coronavirus-infected diseases, and attempts to construct the pathological spectrum of coronavirus-infected diseases, aiming to provide reference and thinking for autopsy, histopathological examination and animal infection model study of coronavirus-infected diseases.

Review and Prospects of Pathogen Detection Related to Autopsy of Coronavirus Infectious Diseases / 法医学杂志

In the past, coronavirus caused two serious human-to-human pandemics in the world, including severe acute respiratory syndrome （SARS） and Middle East respiratory syndrome （MERS）. In late 2019, coronavirus disease 2019 （COVID-19） caused another major global public health event. Due to the strong infectivity of novel coronavirus, it is difficult to carry out the autopsy of related death cases widely. This paper reviews the previous status of the pathogen detection related to the autopsy of coronavirus infection diseases, and introduces the ongoing detection methods of novel coronavirus in clinical practice, in order to provide reference for the pathogen detection and study related to autopsy of COVID-19.

Correlation between Abdominal Wall Subcutaneous Fat Thickness and Heart Weight in Southern Chinese Population / 法医学杂志

Objective To study the correlation between the abdominal wall subcutaneous fat thickness and heart weight, so as to provide reference for prediction methods of normal range of heart weight that is suitable for autopsy in China. Methods The forensic pathology autopsy cases accepted by Center for Medicolegal Expertise of Sun Yat-sen University from 1998 to 2017 were collected. Then the exclusion criteria were determined, and according to them the total case group was selected, and the 6 disease groups and the normal group were further selected from the total case group. The rank sum test was used to compare the heart weight of the normal group and the disease groups to determine the influence of diseases on heart weight. Then the Spearman rank correlation analysis of abdominal wall subcutaneous fat thickness and heart weight in different genders and different ages in the total case group and the normal group was conducted to get the correlation coefficient （rs）. Results In the total case group, correlation between abdominal wall subcutaneous fat thickness and heart weight was shown in males of all ages （P<0.05）; while in females, the correlation had no statistical significance （P>0.05） in 15-<20 age and 50-<60 age, but was statistically significant （P<0.05） in other age groups. For the males in the normal group, rs was respectively 0.411, 0.541 and 0.683 in the 15-<40 age, the 40-<60 age, and the ≥60 age. For the females, rs was respectively 0.249 and 0.317 in the 15-<40 age and the 40-<60 age. The correlation in the ≥60 age had no statistical significance（P>0.05）. Conclusion In the general population and the normal population, abdominal wall subcutaneous fat thickness is correlated with the heart weight of males. It is of significance to include the abdominal wall subcutaneous fat thickness in the prediction of normal range of heart weight for males in China.

Minimum Eigenvector Collaborative Representation Discriminant Projection for Feature Extraction.

High-dimensional signals, such as image signals and audio signals, usually have a sparse or low-dimensional manifold structure, which can be projected into a low-dimensional subspace to improve the efficiency and effectiveness of data processing. In this paper, we propose a linear dimensionality reduction method-minimum eigenvector collaborative representation discriminant projection-to address high-dimensional feature extraction problems. On the one hand, unlike the existing collaborative representation method, we use the eigenvector corresponding to the smallest non-zero eigenvalue of the sample covariance matrix to reduce the error of collaborative representation. On the other hand, we maintain the collaborative representation relationship of samples in the projection subspace to enhance the discriminability of the extracted features. Also, the between-class scatter of the reconstructed samples is used to improve the robustness of the projection space. The experimental results on the COIL-20 image object database, ORL, and FERET face databases, as well as Isolet database demonstrate the effectiveness of the proposed method, especially in low dimensions and small training sample size.

A Robust Nonrigid Point Set Registration Method Based on Collaborative Correspondences.

The nonrigid point set registration is one of the bottlenecks and has the wide applications in computer vision, pattern recognition, image fusion, video processing, and so on. In a nonrigid point set registration problem, finding the point-to-point correspondences is challengeable because of the various image degradations. In this paper, a robust method is proposed to accurately determine the correspondences by fusing the two complementary structural features, including the spatial location of a point and the local structure around it. The former is used to define the absolute distance (AD), and the latter is exploited to define the relative distance (RD). The AD-correspondences and the RD-correspondences can be established based on AD and RD, respectively. The neighboring corresponding consistency is employed to assign the confidence for each RD-correspondence. The proposed heuristic method combines the AD-correspondences and the RD-correspondences to determine the corresponding relationship between two point sets, which can significantly improve the corresponding accuracy. Subsequently, the thin plate spline (TPS) is employed as the transformation function. At each step, the closed-form solutions of the affine and nonaffine parts of TPS can be independently and robustly solved. It facilitates to analyze and control the registration process. Experimental results demonstrate that our method can achieve better performance than several existing state-of-the-art methods.

Analysis of Chemical Variability on Different Processed Products of Glycyrrhiza uralensis Dry Roots and Rhizomes Based on UPLC-Q-TOF-MSE and Plant Metabolomics / 中国实验方剂学杂志

Objective:To identify the quality differential markers of different processed products of Glycyrrhiza uralensis dry roots and rhizomes. Method:Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MSE) was used to collect high-precision mass-charge ratio and ion response strength information of the components in G. uralensis dry roots and rhizomes before and after processing by negative ion mode. The data set collected after pretreatment was analyzed with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to quickly search the differential components in different processed products of G. uralensis dry roots and rhizomes. Differential components were identified according to the relative molecular weight, fragment ion, mass spectrum database and related literature information, then the migration of components before and after processing was studied. Result:A total of 10 quality differential markers were searched from raw products, roasted products and honey-roasted products of G. uralensis dry roots and rhizomes, mainly derivatives of liquiritin and glycyrrhizic acid. Among them, the contents of 6''-O-acetylliquiritin apioside, 6''-O-acetylliquiritin apioside isomer, 6''-O-acetylliquiritin, formononetin and 11-deoxo-18β-glycyrrhetic acid were the highest in the raw products, the contents of 6''-O-acetylisoliquiritin apioside, 6''-O-acetylisoliquiritin, isoliquiritin and glycyrrhetic acid 3-O-glucuronide were the highest in the roasted products, the content of liquiritin was the lowest in the honey-roasted products. Conclusion:There are some chemical differences among the three products. This study can provide material basis for the quality control and pharmacodynamic research of processed products of G. uralensis dry roots and rhizomes.

Analysis on epidemiological and spatio－temporal characteristics of hand，foot and mouth disease in Yunnan Province from 2014 to 2018 / 中华疾病控制杂志

@#Objective To analyze the epidemic situation and characteristics of spatial autocorrelation and spatiotemporal regular of hand，foot and mouth disease( HFMD) in Yunnan Province during the period from 2014 to 2018，thus to provide theoretical basis for HFMD prevention and control． Methods Descriptive epidemiologic method was used to analyze the epidemic situation of HFMD，spatial autocorrela- tion was used to analyze the spatial cluster aggregation，and discrete Possion model in spatio－temporal in scan was used to detect HFMD＇s spatio－temporal clustering condition． Ｒesults The incidence of HFMD in Yunnan Province had been risen rapidly during the past 5 years． Cases mainly occurred among the group of male，0－4 years old group and scattered children． The predominant pathogen had changed，Other enterovir- us gradually replaced enterovirus 71( EV71) to be the predominant． HFMD cases and pathogen showed sig- nificant spatial clustering aggregation，HFMD cases hot spots mainly concentrated in the central and south－ central part of Yunnan Province． The amount of EV71 cases hot spots increased gradually，and the hot spot areas augmented and extended to the central and south－central part of Yunnan Province． There was obvious spatial－temporal aggregation of HFMD，annual scan results detected 3 first－level cluster areas and 1 second －level cluster area． Clustering time was mainly concentrated in April to October of each year． Conclusions Distribution characteristics of HFMD among people in Yunnan Province did not change significantly during the period from 2014 to 2018，while the proportion of pathogenic spectrum changed significantly． The key areas of HFMD control and prevention were still in the central and central－south part of Yunnan Province，while the aggregation and break of HFMD in these areas from April to October should be concerned．

Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） / 法医学杂志

Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 （COVID-19） and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.

Discussion on Research and Development of Following Original Methods of Famous Classical Formulas——Taking Xiebaisan as an Example / 中国实验方剂学杂志

The National Medical Products Administration intends to simplify the registration and approval process of the classic Chinese herbal compound preparations that meet the requirements, but it is a prerequisite for obtaining preferential policies that the preparation method and the route of administration are consistent with the records of ancient medical books. As most of the famous classical formulas are recorded in the medical books of the Qing dynasty and before the Qing dynasty, during the use of medicinal materials in various dynasties, the processing of herbs, dose of medicinal herbs, and the method of decocting may have changed. If researchers simply adopt modern methods to study the formula, it is easy to deviate from policy requirements. The strengthening of preliminary data survey and definition of prescription component and the medication situation of the dynasties can provide strong theoretical support for the study of famous classical formulas. Based on this, the authors take Xiebaisan as an example, which being collected in the First Batch of Catalogue of Ancient Classical Formulas. By following the principles of ancient methods, the research and development ideas of the classic Chinese herbal compound preparations were expounded from the aspects of origin of medicinal materials, processing of medicinal materials, preparation of standard decoction and quality standard of Xiebaisan granules, so as to provide a referential method for the development and research of the famous classical formulas.

Strategy of the Causes of Death of Dependents / 法医学杂志

Objective To discuss the methods and strategies to identify the causes of dependents' deaths, as well as provide the experiences that can be used for reference and scientific basis for the forensic identification of the potentially growing deaths of the same kind in the future. Methods The 13 cases concerning death of dependents accepted by Sun Yat-sen University Forensic Center were collected, and the basic information of the dependents were statistically described. The nutritional status, environmental condition and medical care condition were evaluated according to dietary energy, living space, environment and medical treatment condition. Results Among the 13 dependents, there were 11 males and 2 females, with the oldest 74 and the youngest 9 and dwelling time was from 0.4 to 5.6 years. Forensic pathological examination showed that 13 dependents had infectious diseases and 11 were severely dystrophic. There were no fatal mechanical injuries or poisoning in dependents. Molecular pathological screening of 4 cases revealed no pathogenic variants of sudden death susceptible genes. The poor status of the diet, nutrition, living environment and medical care of these dependents were discovered. The direct cause of death of all 13 dependents was identified to be disease. The lack of nutrition, poor living environment and lack of medical care were thought to play a dominant role in causing the deaths of 12 dependants. Conclusion The death identification should follow the judicial procedure. In identification of the causes of death and analysis of the proportion of the affecting factors resulting in death, all factors, including nutrition,environment, medical care, injury and diseases, need to be considered.

Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai powder injection in rats with chronic heart failure by UFLC-MS/MS.

YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese medicine (TCM) formula Shengmai San, is a modern preparation widely used to combat cardiovascular diseases, chronic heart failure (CHF) for example, in clinical practice in China. Ginsenosides are the major components of YQFM, which are responsible for its therapeutic effect. In this research, we developed a rapid, sensitive and simple method for simultaneous determination of ten ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). After solid phase extraction (SPE), chromatography was done on an Acquity UPLC HSS T3 column (1.8µm, 100mm×2.1mm, i.d.) through an 8.0min gradient elution with acetonitrile and 0.1% formic acid in water, while mass spectrometry was performed in the positive ion electrospray ionization (ESI) mode. A good linearity was achieved for each analyte with correlation coefficient (r) >0.9920. The lower limits of quantification (LLOQ) were 1.25ng/mL for ginsenoside Rg1, Rd, Re and Rh1, 2.5ng/mL for ginsenoside Rf, Rg3, Rb2 and Rb3 and 5.0ng/mL for ginsenoside Rb1 and Rc, respectively. All the precision (RSD) data ranged from 1.7-14.5% and the accuracy (RE) data was within ±13.73%. Moreover, the validated method has been applied to investigate the integrated pharmacokinetic profiles of ginsenosides in CHF rats following intravenous administration of YQFM successfully.

Microarray expression profiling of long non-coding RNAs in epithelial ovarian cancer.

Although numerous long non-coding RNAs (lncRNAs) have been identified to be important in human cancer, their potential regulatory roles in epithelial tumorigenesis and tumor progression in ovarian cancer remain unclear. The purpose of the present study was to investigate lncRNAs that were differentially expressed (DE) in epithelial ovarian cancer and to explore their potential functions. The lncRNA profiles in five pairs of human epithelial ovarian cancer tissues and their adjacent normal tissues were described using microarrays. The results of the microarray analysis revealed that 672 upregulated and 549 downregulated (fold-change ≥2.0) lncRNAs were DE between the cancerous and normal tissues. Reverse transcription-quantitative polymerase chain reaction was used to validate the microarray results using four upregulated (RP11-1C1.7, XLOC_003286, growth arrest-specific 5 and ZNF295-AS1) and four downregulated (protein tyrosine kinase 7, maternally expressed gene 3, AC079776.2 and ribosomal protein lateral stalk subunit P0 pseudogene 2) lncRNAs. Furthermore, gene ontology and pathway analyses were used to carry out functional analyses of the candidate genes of DE lncRNAs. The results identified lncRNAs with significantly altered expression profiles in human epithelial ovarian cancer cells compared with those in adjacent normal cells. These data offer new insights into the occurrence and development of epithelial ovarian cancer, and these lncRNAs may provide novel molecular biomarkers for further research on epithelial ovarian cancer.

Comparatively evaluating the pharmacokinetic of fifteen constituents in normal and blood deficiency rats after oral administration of Xin-Sheng-Hua Granule by UPLC-MS/MS.

Xin-Sheng-Hua Granule (XSHG), a famous traditional Chinese medicine prescription, are clinically applied for the treatment of postpartum disease through nourishing blood and promoting blood circulation. In this investigation, a multi-constituents (trigonelline, stachydrine hydrochloride, hydroxysafflor yellow A, chlorogenic acid, amygdalin, leonurine, liquiritin, ferulic acid, senkyunolide I, senkyunolide H, glycyrrhizic acid, senkyunolide A, ligustilide, butylidenephthalide and glycyrrhetinic acid) pharmacokinetic study of XSHG was conducted for the first time. These fifteen constituents in both normal and blood deficiency rat plasma were monitored by using the established and validated ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UPLC-TQ-MS/MS) method. The samples were prepared through removing protein from plasma with three volumes of methanol. Sufficient separation of target constituents and internal standards (chloramphenicol and clarithromycin) was obtained on a Thermo Scientific Hypersil GOLD column (100mm×3mm, 1.9µm) within a 20min gradient elution (0.1% formic acid aqueous - acetonitrile). Multiple reaction monitoring (MRM) mode was applied to monitor target analytes in both positive and negative electrospray ionization. For the fifteen selected target analytes, this method was fully validated with excellent linearity (r≥0.9925), satisfactory intra- and inter-day precisions (RSD≤11.87%), as well as good accuracies (RE, between -12.84 and 11.69). And the stabilities, matrix effects and extraction recoveries of the rat plasma samples were also within acceptable limits (RSD<15%). Compared to normal group, the pharmacokinetics of major active constituents (except liquiritin and glycyrrhetinic acid) had significant differences (P<0.05) in the model rats, indicated that several metabolite enzymes activities could be altered at disease condition.

Influence of ultrafiltration membrane on ophiopogonins and homoisoflavonoids in Ophiopogon japonicus as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry.

Ultrafiltration is one of the most fascinating technologies, which makes it possible to improve the quality of traditional medicines for application in the pharmaceutical industry. However, researchers have paid little attention to the effect of ultrafiltration membrane on traditional medicines chemical constituents. In this work, Ophiopogon japonicus (L.f) Ker-Gawl. was used as an example to illuminate the influence of ultrafiltration with different material and molecular weight cut-off (MWCO) membrane on natural chemical constituents as measured by ultra-fast liquid chromatography coupled with ion trap time-of-flight mass spectrometry (UFLC-IT-TOF/MS). Our results indicated that ultrafiltration membrane significantly impacted homoisoflavonoids, especially homoisoflavonoids that were almost completely retained on the polyethersulfone (PES) membrane. We also found that the larger number of aglycone hydroxy and sugar moiety in steroid saponins, the higher the transmittance. Furthermore, the passage rate (%) of ophiogenin type saponins was higher than that of others. The possible adsorptive mechanisms were hydrogen bonding, hydrophobic interactions, and benzene ring interaction by π-π stacking. In conclusion, it is crucial to choose appropriate ultrafiltration membrane based on the characteristics of produce products for application of ultrafiltration technique.