Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 μm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review / 中国中药杂志

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Simultaneous determination of seven components and their distribution in Anoectochilus roxburghii by UHPLC-MS/MS / 药学学报

Based on ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), a rapid and simultaneous quantitative method for the measurement of seven components (kinsenoside; rutin; kaempferol-3-O-rutinoside; quercimeritrin; narcissin; isorhamnetin-3-O-glucoside; quercetin) of A. roxburghii was established. The separation was performed over 8.0 minutes on a Waters Acquity UPLC BEH Shield RP18 (2.1 mm × 100 mm; 1.7 μm) with a mobile phase consisting of acetonitrile (A) and 0.1% formic acid water solution (B) with gradient elution at a flow rate of 0.2 mL·min-1; the column temperature was 30 ℃ and the injection volume was 2 μL. Electrospray spray ionization source (ESI source) was used for mass spectrometry, and positive and negative ion modes were detected at the same time. The results showed good linearity (R2 ≥ 0.998 0), with good precision, repeatability and stability, and the average recovery was 97.71%-103.33%. Through cluster heat map and redundancy analysis, we found that kinsenoside was mainly distributed in stems, followed by leaves, and the lowest content in roots. The content of kinsenoside increased significantly in the stems of plants 6 months, but less change was evident in the roots and leaves. Flavonoids and flavonoid glycosides were mainly distributed in leaves. The UHPLC-MS/MS method established in this paper can be used for the quality control of A. roxburghii and provides a reference for establishing a more comprehensive quality detection method for this medicinal.

Quality evaluation of Lysimachiae Herba from different habitats based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis / 中国中药杂志

A method based on ultra-high performance liquid chromatography coupled with triple quadrupole linear ion trap-tandem mass spectrometry(UHPLC-QTRAP-MS/MS) was developed for the simultaneous determination of 41 bioactive constituents of flavonoids, organic acids, nucleosides, and amino acids in Lysimachiae Herba. The content of multiple bioactive constituents was compared among the samples from different habitats. The chromatographic separation was performed in a Waters XBridge®C_(18) column(4.6 mm×100 mm, 3.5 μm) at 30 ℃. The gradient elution was performed with 0.4% methanol(A)-formic acid water(B) as the mobile phase at a flow rate of 0.8 mL·min~(-1), and the multiple-reaction monitoring(MRM) mode was adopted. According to the content of 41 constituents, hierarchical cluster analysis(HCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and gray relational analysis(GRA) were perfomed to comprehensively evaluate the samples from different habitats. The results showed that the 41 constituents exhibited good linear relationship within the tested concentration ranges, with the correlation coefficients(r) greater than 0.999 4. The method featured good precision, repeatability, and stability with the relative standard deviations(RSDs) less than 5.0%. The average recoveries of the 41 constituents ranged from 98.06% to 101.9%, with the RSDs of 0.62%-4.6%. HCA and OPLS-DA separated 48 batches of Lysimachiae Herba samples from different habitats into three categories: the producing areas in Sichuan and Chongqing, the producing areas in Jiangsu, Zhejiang, and Jiangxi, and the producing areas in Guizhou. The content of 41 constituents varied among the Lysimachiae Herba samples from different habitats. The GRA results revealed that the Lysimachiae Herba sample from Nanchong City, Sichuan Province had the best comprehensive quality. The method developed in this study was accurate and reliable and thus can be used for comprehensive evaluation of Lysimachiae Herba quality and provide basic information for the selection of habitats.

Abnormal coagulation activity and the related clinical significance in patients with novel bunyavirus infection / 中华检验医学杂志

Objective:To explore the related indexes of coagulation and thrombosis and their clinical significance in patients with severe fever with thrombocytopenia symptoms (SFTS) during the onset and recovery period after novel bunyavirus infection.Methods:A total of 36 patients diagnosed with SFTS (SFTS onset group) and 18 convalescent SFTS patients, who were hospitalized in the First Affiliated Hospital of Anhui Medical University from April 12, 2020, to October 12, 2020 were recruited in this study. Thirty-six healthy controls were recruited from volunteers. Plasma was collected and prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time(TT), antithrombin-Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and D-dimer (D-D) were determined by automatic blood coagulation analyzer. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminase-α2 plasminase inhibitor complex (PIC) and tissue plasminogen activator-plasminogen activator inhibitor 1 complex (t-PAIC) were determined by an automatic chemiluminescence analyzer.Results:Compared with the healthy control group, PT was significantly prolonged (12.5 [12.1, 13.6] s, vs 10.8 [10.5, 11.5] s, P<0.05) in SFTS onset group, but was still within the reference range (14.0-21.0 s), and APTT (49.1 [42.0, 58.2]s vs 28.5 [26.6, 30.4]s, P<0.05) was also significantly prolonged in SFTS onset group. Compared with healthy control group, FDP (6.07 [2.67, 8.64] μg/ml vs 1.00 [0.80, 1.87] μg/ml, P<0.001), D-D (2.27 [1.04, 2.98] μg/ml vs 0.30 [0.21, 0.47] μg/ml, P<0.001), TAT (16.05 [8.05, 26.58] ng/ml vs 3.55 [2.60, 4.85] ng/ml, P<0.001), PIC (4.44 [2.52, 5.54] μg/ml vs 0.84 [0.60, 1.35] μg/ml, P<0.001), TM ([19.41±8.29] TU/ml vs [9.33±1.89] TU/ml, P<0.001), and t-PAIC ([37.52±21.10] ng/ml vs [7.06±3.37] ng/ml, P<0.001) values were all significantly higher in the SFTS onset group (all P<0.001). The level of TAT in the SFTS recovery group (9.10 [3.95, 18.40] ng/ml) was still out of the reference range (<4 ng/ml), while the level of PIC in the SFTS recovery group was lower than in SFTS onset group (1.91 [1.45, 2.93] μg/ml vs 4.44 [2.52, 5.54] μg/ml, P<0.05). Compared with SFTS onset group, the levels of TM and t-PAIC were lower in the SFTS recovery group ( P<0.05). Conclusions:Coagulation system activation and vascular endothelial injury are evidenced in SFTS patients. In the convalescence period, the vascular endothelial injury is recovered, however, there is still a certain degree of coagulation dysfunction, therefore, it is necessary to monitor the coagulation indicator of discharged patients post SFTS.

Cloning and prokaryotic expression analysis of AlCMK from Atractylodes lancea / 药学学报

4-(Cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) was one of the key enzymes in the methylerythritol-4-phosphate (MEP) pathway to generate terpenoids. In this study, based on the transcriptome data of Atractylodes lancea, the sequence of the CMK gene was cloned, named AlCMK (GenBank accession number OM283293). The results showed that AlCMK contains a 1 230 bp open reading frame (ORF) encoding 409 amino acids. The deduced protein had a theoretical molecular weight of 44 752.53 and an isoelectric point of 6.67. Transmembrane structure analysis showed that there was no transmembrane structure, and the secondary structure of AlCMK was predicted to be mainly composed of random coil. Homologous alignment revealed that AlCMK shared high sequence identity with the CMK proteins of Tanacetum cinerariifolium, Osmanthus fragrans, Eucommia ulmoides, Lonicera japonica and Salvia miltiorrhiza. Phylogenetic analysis indicated that AlCMK protein had the higher homology with CMK protein of Compositae. The pET-32a-AlCMK prokaryotic expression vector was constructed and a fusion protein with molecular mass of about 65 kDa was expressed in the E. coli BL21 (DE3). The qRT-PCR was used to analyze the expression pattern of AlCMK gene in different tissues and after MeJA treatment. Meanwhile, the enzyme activity was determined by ELISA kit. The results showed that AlCMK gene was tissue-expressed in different origins and its expression was induced by MeJA, and the results of the enzyme activity assay showed that the AlCMK enzyme activity in different regions was higher in the leaves. The subcellular localization showed that AlCMK was located in the chloroplast. This study provides a reference for further elucidating the biological function of AlCMK gene in terpenoid synthesis pathway in Atractylodes lancea.

Resource characteristics and propagation techniques of Anoectochilus roxburghii in China / 药学学报

italic>Anoectochilus roxburghii (Wall.) Lindl. is a medicinal species belonging to the Orchidaceae, whose whole plant can be used as a medicinal herb, known as "JinXianLian". It has antidiabetic, liver-protecting, anti-inflammatory, etc. A. roxburghii has long been used as food and medicine in Guangdong and Fujian provinces. With the wide recognition of the concept of "medicine and food homology" and the surge of market demand, wild A. roxburghii has been far from meeting the supply. It is important to establish an artificial propagation system. Resource characteristics are the key basis for optimizing germplasm and propagation systems. Therefore, this paper summarizes the germplasm resource characteristics and propagation technologies of A. roxburghii in China to provide a reference for sustainable development and subsequent mechanistic research.

Intelligent Screening of Pieces of Chinese Medicine Based on BMFnet-WGAN / 中国实验方剂学杂志

Objective:To explore the feasibility of machine vision and deep learning methods in intelligent screening of pieces of Chinese medicine， so as to meet the needs of modern screening of pieces of Chinese medicine and overcome the problems of strong subjectivity and low efficiency in traditional screening based on manual experience. Method:An image set containing 11 125 images for 60 kinds of pieces of Chinese medicine was constructed， and the network architectures for high- and low-frequency feature learning were designed. Specifically， the parallel convolutional network was employed to obtain the low frequency feature and the deep multi-scale convolutional neural network to uncover the high-frequency feature. The semantic network was used to realize the feature learning mode with generalization ability. In this study， Wasserstein distance was introduced into the generative adversarial networks （GANs） to complete the screening of pieces of Chinese medicine， and the conditional parameters were added to the generation and discrimination networks to make the network training more reliable and improve the accuracy of identification. Result:The experiment results showed that when the ratio of training samples to test samples was greater than 6∶4， the identification accuracy of pieces of Chinese medicine was relatively stable. The identification accuracy of images captured in different states and environments by bi-view multi-feature network Wasserstein generative adversarial network （BMFnet-WGAN） reached up to 85.9% on average and the stability was high， demonstrating that BMFnet-WGAN was superior to VGG-Net and AlexNet. Conclusion:The BMFnet-WGAN method enables the revealing of rich and typical characteristics of decoction pieces and the introduced WGAN model and Wasserstein distance make the network training more reliable. The resulting accuracy， robustness， and batch effects in the intelligent screening of pieces of Chinese medicine were good， which has provided the technical support for the sorting and quantitative quality screening of pieces of Chinese medicine.

Simultaneous determination of multiple bioactive constituents in Abelmoschi Corolla by UFLC-QTRAP-MS/MS / 中国中药杂志

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 38 active components in Abelmoschi Corolla, including flavonoids, organic acids, nucleosides and amino acids, so as to investigate the effects of different harvesting and processing methods on multi-active components in Abelmoschi Corolla. The chromatographic separation was performed on a XBridg®C_(18) column(4.6 mm×100 mm, 3.5 μm) with(0.1% formic acid water) methanol-acetonitrile(1∶1) as the mobile phase for gradient elution at 30 ℃. The flow rate was 0.5 mL·min~(-1). The components were detected in a multiple-reaction monitoring(MRM) mode. The gray relational analysis(GRA) was used to comprehensively evaluate the multiple active components of Abelmoschi Corolla at different harvesting times and drying temperatures. The results showed that 38 components had a good linearity with correlation coefficients all above 0.999 0. The method featured a good precision, repeatability and stability with the relative stan-dard deviations(RSDs) of less than 5.0%. Recoveries ranged from 98.06% to 104.4% with RSD between 0.22% and 4.9%. The results of GRA indicated that a better quality in the samples collected on September 9 th. Samples dried at 90 ℃ had a better quality. The established method is accurate and reliable, and can be used to assess the internal quality of Abelmoschi Corolla. This study can provide basic materials for determining appropriate harvesting time and processing method of Abelmoschi Corolla.

Mid-term outcome after tricuspid valve replacement

Abstract Objective: To evaluate the mid-term survival rate after tricuspid valve replacement (TVR). Methods: We retrospectively studied 110 consecutive patients who underwent TVR from January 2007 to November 2017. A survival analysis was performed with the Kaplan-Meier method and the log-rank test. Results: The median survival was 65.81 months. Mean age was 50 (range 39 to 59) years. Forty-eight patients (43.6%) were male, and 62 patients (56.4%) were female. Most of the patients (78.5%) were categorized into the New York Heart Association (NYHA) functional classes III/IV. Seventy-two patients (65.5%) had isolated TVR. Six-three patients (57.3%) had previously undergone heart surgery. The Kaplan-Meier survival rates at one year, three years, and five years were 59.0%±5%, 52.0%±6%, and 48.0%±6%, respectively. A Cox regression analysis demonstrated that the risk factors for mid-term mortality were advanced NYHA class (hazard ratio [HR] 2.430, 95% confidence interval [CI] 1.099-5.375, P=0.028), need for continuous renal replacement therapy (CRRT) treatment (HR 3.121, 95% CI 1.610-6.050, P=0.001), and need for intra-aortic balloon pump (IABP) treatment (HR 3.356, 95% CI 1.072-10.504, P=0.038). Conclusion: In TVR, impaired cardiac function before the operation and a need for CRRT or IABP treatment after the operation is independently associated with increased mid-term mortality.

Effect of Bletillae Rhizoma Polysaccharide on PI3K/Akt in Gastric Tissue of GU Model Rats / 中国实验方剂学杂志

Objective::To investigate the effect of Bletillae Rhizoma polysaccharide on the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) gene protein and its mediated cytokines interleukin-2 receptor (IL-2R) and interleukin-4 (IL-4) in gastric tissue of rats with gastric ulcer (GU). Method::Sixty SPF Wistar rats were randomly divided into blank group and model group.The GU model was replicated by direct acetic acid cauterization in model group.The GU model rats were randomly divided into five groups: model group, positive control group, and large, medium and small-dose Bletillae Rhizoma polysaccharide groups, with 10 rats in each group.Rats in blank group and GU model group were given 10 mL·kg-1·d-1 distilled water by gavage, rats in large, medium and small-dose groups were given 0.5, 0.25, 0.125 g·kg-1·d-1 Bletillae Rhizoma polysaccharide by gavage, while rats in positive control group were given 0.3 g·kg-1·d-1 ranitidine by gavage for 15 days.Serum nitric oxide (NO) content, pepsinase activity and cytokines IL-2R and IL-4 levels in rats of each group were measured by enzyme-linked immunosorbent assay (ELISA), PI3K and Akt mRNA expressions were detected by Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and PI3K and Akt protein expressions were detected by Western blot. Result::Compared with the blank group, the contents and gene expressions of cytokines IL-2R and IL-4 in gastric tissue were significantly increased, and the PI3K and Akt genes and protein expressions were significantly increased, with statistical significance (P<0.01). Compared with GU model group, the content and gene expressions of IL-2R and IL-4 in large, medium and small-dose Bletillae Rhizoma polysaccharide groups were decreased significantly, and the PI3K and Akt gene and protein expressions were decreased significantly in large-dose Bletillae Rhizoma polysaccharide group, while those in large and medium-dose Bletillae Rhizoma polysaccharide groups were decreased significantly (P<0.05, P<0.01). Conclusion::Bletillae Rhizoma polysaccharide can protect gastric mucosa by down-regulating PI3K and Akt gene and protein expressions and inhibiting abnormal secretion of cytokines IL-2R and IL-4.

Analysis and evaluation of dynamic accumulation of multiple bioactive constituents in Spatholobi Caulis / 中国中药杂志

A method was established for simultaneous determination of 21 active constituents including flavanols, isoflavones, flavonols, dihydroflavones, dihydroflavonols, chalcones, pterocarpan, anthocyanidins and phenolic acids in Spatholobi Caulis by ultra fast liquid chromatography with triple quadrupole linear ion trap mass spectrometry(UFLC-QTRAP-MS/MS). Then, it was employed to analyze and evaluate the dynamic accumulation of multiple bioactive constituents in Spatholobi Caulis. The chromatographic separation was performed on a XBridge®C_(18)(4.6 mm×100 mm, 3.5 μm) at 30 ℃ with a gradient elution of 0.3% formic acid aqueous solution-methanol, and the flow rate was 0.8 mL·min~(-1), using multiple-reaction monitoring(MRM) mode. A comprehensive evaluation of the multiple bioactive constituents was carried out by gray correlation analysis(GRA). The 21 target components showed good linearity(r>0.999 0) in the range of the tested concentrations. The average recovery rates of the 21 components were from 97.46% to 103.6% with relative standard deviations less than 5.0%. There were differences in the contents of 21 components in Spatholobi Caulis at diffe-rent harvest periods. Spatholobi Caulis had high quality from early November to early December, which is consistent with the local tradi-tional harvest period. This study reveals the rule of the dynamic accumulation of 21 components in Spatholobi Caulis and provides basic information for the suitable harvest time. At the same time, it provides a new method reference for the comprehensive evaluation of the internal quality of Spatholobi Caulis.

Qualitative evaluation of Forsythia suspensa by HPLC-PDA fingerprint combined with UFLC-Q-TOF-MS qualitative identification / 中国中药杂志

The analysis of Forsythia suspensa was performed on Waters Symmetry C18 column( 4. 6 mm×250 mm,5 μm) and mobile phase was methanol( A)-0. 1% formic acid aqueous solution( B) with the elution gradient. Column temperature was maintained at 30℃,and the flow rate was 1. 0 m L·min-1 with detection wavelength 265 nm. The HPLC-PDA fingerprint of F. suspensa was optimized.Chemical constituents in F. suspensa were analyzed by UFLC-Q-TOF-MS in positive and negative ion mode. The quality of 48 batches of F. suspensa from different habitats,processing methods and specifications was evaluated by similarity evaluation and cluster analysis.The 18 common peaks were confirmed. The similarity of F. suspensa from different habitats was more than 0. 98,and 56 chemical constituents were identified. Different processing methods had great influence on the quality of F. suspensa. Compared with boiled and direct drying,the quality of F. suspensa processed by sun-drying was obviously decreased. The similarity was about 0. 58. Different specifications of F. suspensa also had obvious distinction,and the similarity was about 0. 78. The effective components of grown F. suspensa,such as forsythoside A and phillyrin,were significantly reduced. The results of cluster analysis were basically consistent with the results of similarity evaluation. The establishment of fingerprint and the recognition of chemical pattern of F. suspensa can provide a more comprehensive reference for the quality control of herbs.

Comparison on local dengue fever outbreaks in public place in Shenzhen and Hong Kong in 2018 / 中华疾病控制杂志

Objective To compare epidemiology characteristics and control measures of dengue fever (DF) outbreaks in public places in Shenzhen and Hong Kong and integrate the advantages for better response to DF outbreaks. Methods Data of DF cases and mosquito vector surveillance in Shenzhen and Hong Kong were collected for descriptive epidemiological analysis and measures of mosquito control were compared. Results A total of 19DF cases were recorded in 13 d among six districts of Hong Kong, the male: female ratio was 1 ∶〗0.9. In Shenzhen, 20 cases were recorded in 33 d, the cases were distributed in three sub-districts, the Male: female ratio was 1 ∶〗0.82; Age difference between Shenzhen and Hong Kong was statistically significant (Z=-2.855, P=0.004). The time interval between date of onset and laboratory confirmation ranging from 5.5 to 8.5 d (median:7d) in Hong Kong, and ranged from 1.5 to 5.4 d (median:2 d) in Shenzhen, the difference was statistically significant (Z=-3.818, P<0.001). On the 4th day of the outbreak, Hong Kong declared 30 d closure for anti-mosquito operations with a range of 500 m, and monthly area ovitrap index (AOI) was used to monitor the territory-wide situation of Aedes albopictus. On the 2nd day of the outbreak, Shenzhen declared source closure for mosquito control with a range of 400 m and emergency vector surveillance was conducted, using Breteau Index (BI) and Human-baited double net trap(HDN) every 3 d. Conclusions The nature, scale, time and place of the two local DF outbreaks in Shenzhen and Hong Kong are similar. The prevention and control system is more sensitive and prompt, the ability of early detection is stronger, mosquito vector surveillance program is more comprehensive and the frequency is higher in Shenzhen. The epidemic information dissemination and risk communication with media is more active, mosquito management and control is more professional in Hong Kong.

Relationships between female infertility and female genital infections and pelvic inflammatory disease: a population-based nested controlled study

OBJECTIVES: Our purpose was to examine the associations of female genital infections and certain comorbidities with infertility. METHODS: The Taiwan National Health Research Database was searched for women with a new diagnosis of infertility between 2000 and 2013. Women without a diagnosis of infertility served as a control group and were matched with the infertility cases by age (±3 years) and index year. They were divided into two groups: ≤40 years old and >40 years old. Univariate and multivariate conditional logistic regression models were employed to identify the risk factors associated with infertility. RESULTS: A total of 18,276 women with a new diagnosis of infertility and 73,104 matched controls (mean cohort age, 31±6.2 years) were included. According to the adjusted multivariate analysis, pelvic inflammatory disease involving the ovary, fallopian tube, pelvic cellular tissue, peritoneum (odds ratio (OR)=4.823), and uterus (OR=3.050) and cervical, vaginal, and vulvar inflammation (OR=7.788) were associated with an increased risk of infertility in women aged ≤40 years. In women aged >40 years, pelvic inflammatory disease of the ovary, fallopian tube, pelvic cellular tissue, and peritoneum (OR=6.028) and cervical, vaginal, and vulvar inflammation (OR=6.648) were associated with infertility. Obesity, lipid metabolism disorders, dysthyroidism, abortion (spontaneous or induced), bacterial vaginosis, endometritis, and tubo-ovarian abscess were associated with an increased risk of infertility according to the univariate analysis but not the multivariate analysis. CONCLUSIONS: Female genital tract infections, but not the comorbidities studied here, are associated with an increased risk of infertility.

Simultaneous determination of lignans and organic acids in Schisandrae Chinensis Fructus by UFLC-Q-TRAP-MS/MS / 中国中药杂志

An analytical method based on UFLC-QTRAP-MS/MS was developed for simultaneous determination of fifteen components including eleven lignans (schizantherin B, schisandrol B, schizandrin C, γ-schisandrin, deoxyschizandrin, schisantherin, schisandrin, schisanhenol, gomisin D, gomisin J, and angeloylgomisin H) and organic acids (S)-malic acid, D(-)-tartaric acid, protocatechuic acid, and quinic acid) in Schisandrae Chinensis Fructus. Samples from different product specifications were evaluated and analyzed. The chromatographic separation was performed on a Synergi™ Hydro-RP 100Å column (2.0 mm×100 mm, 2.5 μm) at 40 °C with a gradient elution by employing 0.1% aqueous formic acid (A)-acetonitrile (B) as the mobile phase, and the flow rate was 0.4 mL·min⁻¹, using an electrospray ionization (ESI) source and multiple reaction monitoring (MRM) mode. Fifteen components were evaluated synthetically by TOPSIS and gray related degree. The results showed that fifteen components had good linearity (r>0.999 90), and the limits of detection were all satisfactory. The average recoveries of standard addition for the compounds were between 95.42 % and 98.86 %, and the relative standard deviations were less than 5%. The greatest difference of ri in grey related degree was 58.1%, whilst the greatest difference of Ci value in TOPSIS method was 94.8%. The results of these two methods showed that the holistic quality of No. 14 sample was the best. The developed method was accurate and reliable, which was suitable for the simultaneous determination of multiple functional substances and able to provide a new basis for the comprehensive assessment and overall control of the quality of Schisandrae Chinensis Fructus.

Thoughts of omics research on quality formation in Dao-di herbs / 中国中药杂志

Dao-di herbs have been recognized as "quality models" with a firmly stable status. The formation of Dao-di herbs quality is involved from the genetic inheritance on the molecular level to the metabolic phenotype of final products, and the full material-based biosynthetic pathway remains unknown. In recent years, an increasing variety of omics technologies has provided new methods and ideas for the analysis of complex life systems and are suitable for explanation of quality formation in Dao-di herbs as well. In order to alleviate the scarcity of natural resources and offer scientific guidance of transplanting varieties, achievements of omics in the aspects of Dao-di herbs from genetics to phenotyping, the biosynthetic pathway of secondary metabolites, the interaction with human body and the new methods of quality evaluation have been summarized. It will be a fundamental work for protection and utilization of Chinese medicine resources.

Assisted Hatching in Couples with Advanced Maternal Age: A Systematic Review and Meta-analysis / 华中科技大学学报（医学）（英德文版）

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age.We searched for randomized controlled trials (RCTs) in electronic databases,including MEDLINE,EMBASE and CENTRAL (from inception to January 2018);in addition,we hand-searched the reference lists of included studies and similar reviews.We included RCTs comparing AH versus no treatment (control).The meta-analysis was performed by RevMan 5.3 software.The search retrieved 943 records and 8 RCTs were included,comprising 870 cycles (n=440 for AH,and n=430 for control).There was no significant difference in the rates of live birth (RR 0.88,95％ CI 0.65 to 1.18,3 RCTs,n=427,I2=0％),clinical pregnancy (RR 1.00,95％ CI 0.83 to 1.19,8 RCTs,n=870,I2=22％),implantation (RR 1.07,95％ CI 0.83 to 1.39,4 RCTs,n=1359,I2=0％),miscarriage (RR 1.13,95％ CI 0.66 to 1.94,2 RCTs,n=116,I2=0％) and multiple pregnancy (RR 0.89,95％ CI 0.31 to 2.52,1 RCT,n=97,I2=not applicable) between the treatment group and control group.No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses.Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Assisted Hatching in Couples with Advanced Maternal Age: A Systematic Review and Meta-analysis / 华中科技大学学报（医学）（英德文版）

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age.We searched for randomized controlled trials (RCTs) in electronic databases,including MEDLINE,EMBASE and CENTRAL (from inception to January 2018);in addition,we hand-searched the reference lists of included studies and similar reviews.We included RCTs comparing AH versus no treatment (control).The meta-analysis was performed by RevMan 5.3 software.The search retrieved 943 records and 8 RCTs were included,comprising 870 cycles (n=440 for AH,and n=430 for control).There was no significant difference in the rates of live birth (RR 0.88,95％ CI 0.65 to 1.18,3 RCTs,n=427,I2=0％),clinical pregnancy (RR 1.00,95％ CI 0.83 to 1.19,8 RCTs,n=870,I2=22％),implantation (RR 1.07,95％ CI 0.83 to 1.39,4 RCTs,n=1359,I2=0％),miscarriage (RR 1.13,95％ CI 0.66 to 1.94,2 RCTs,n=116,I2=0％) and multiple pregnancy (RR 0.89,95％ CI 0.31 to 2.52,1 RCT,n=97,I2=not applicable) between the treatment group and control group.No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses.Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.