Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Nitrogen fertilizer has been the long-lasting crucial component in cultivation of Chinese materia medica(CMM) and crops for its profound effects on enhancing the productivity. In consideration of its role in better production, intensive and excessive application of N fertilizer is often found in CMM cultivation. Therefore, firstly, this review summarized various concentrations of N application with regards to different CMM and districts from the literatures published in the last two decades. The recommended concentration of nitrogen application of forty seven CMM species were covered in this review. We found that the optimum rates of nitrogen fertili-zer for different medicinal plants species were varied in the range between 0-1 035.55 kg·hm~(-2). Most of the optimum rates of nitrogen fertilizer for CMM in published researches fell between 100-199 kg·hm~(-2). The optimum rate of nitrogen fertilizer is not only related to amount of nitrogen required for different medicinal plants but also to soil fertilities of different fields. In addition, we outlined the diffe-rent effects of proper and excessive nitrogen deposition on yield of CMM. Proper nitrogen deposition benefits the yield of CMM, howe-ver, excessive nitrogen use accounts for a decrease in CMM yield. We elucidated that nutritional content, water use efficiencies, and photosynthesis capacity were major influencing factors. Researches showed that proper nitrogen fertilizer could promote the water use efficiencies of plants and boost photosynthesis. Consequently, the yield of CMM can be enhanced after nitrogen deposition. However, negative effects of nitrogen fertilizer were also found on plant including producing toxic substances to the soil and causing severe pest damages. Lastly we analyzed the impact of N fertilizer application on secondary metabolites which accounts for a large part of active pharmaceutical ingredients of CMM. It usually caused an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. The potential underlying mechanisms are the different synthetic pathways of these metabolites and the plant nutritional status. Synthesis of non-nitrogen-containing secondary metabolites like phenols can be inhibited after nitrogen application because of the competition of the same precursor substances between metabolites synthesis and plant growth. To sum up, impacts and mechanisms of nitrogen fertilizer on yield and quality enhancement of CMM were discussed in this review. Negative effects of excessive nitrogen application on CMM should be paid special attention in CMM cultivation and prescription fertilization based on the field soil quality is strongly recommended. Overall, this review aims to provides insights on improving the proper application of N fertilizer in the cultivation of CMM.
Agriculture ; China ; Fertilizers ; Materia Medica ; Nitrogen/analysis* ; Soil

Nitrogen fertilizers play an important role in the regulation of plant stress resistance. Impacts of nitrogen fertilizers on abiotic stress resistance and biotic stress resistance of Chinese materia medica(CMM) were summarized in this study. Adequate nitrogen application improves the abiotic stress resistance and weed resistance of CMM, however adverse effect appears when excess nitrogen is used. Generally, pest resistance decreases along with nitrogen deposition, while effects of nitrogen application on disease resistance vary with different diseases. Mechanisms underlying the impact of nitrogen fertilizers on plant stress resistance were also elucidated in this study from three aspects including physical defense mechanisms, biochemistry mechanisms and molecular defense mechanisms. Nitrogen availability modulates physical barrier of CMM like plant growth, formation of lignin and wax cuticle, and density of stomata. Growth of CMM promoted by nitrogen fertilizer may cause some decrease in pest resistance of CMM due to an increase in hiding places for pest along with plant growth. High ambient humidity caused by excessive plant growth facilitates the growth and development of CMM pathogen. Nitrogen application can also interfere with the accumulation of lignin in CMM which makes CMM more vulnerable to pest and pathogen attack. Stomatal closing delays due to nitrogen application is also a causal factor of increasing pathogen infection after nitrogen deposition. Biochemical defenses of plants are mainly achieved through nutrient elements, secondary metabolites, defense-related enzymes and proteins. Nutritional level of CMM and various antioxidant enzymes and resistance-related protein activities are elevated along with nitrogen deposition. These antioxidant enzymes can reduce the damage of reactive oxygen species content produced by plant in response to adversity and therefore enhance stress resistance of CMM. Researches showed that nitrogen application could also cause an increase in nitrogen-containing secondary metabolites content and a decrease in non-nitrogen-containing secondary metabolites content respectively. Nitrogen-mediated molecular defense mechanisms includes multiple plant hormones and nitric oxide signals. Plant hormones related to plant defense like salicylic acid, jasmonic acid and abscisic acid can be modulated by nitrogen application. Negative effect of nitrogen deposition was found on salicylic acid accumulation and the expression of related plant disease resistance genes. However, jasmonic acid level can be elevated by nitrogen. Nitric oxide signals constitute an important part of nitrogen mediated defense mechanisms. Nitric oxide signaling is related to many aspects of plant immunity. The roles of nitrogen fertilizers in CMM stress resistance are complex and may vary with different CMM varieties and environments. Further studies are urgently needed to provide a comprehensive understanding of how to improve stress resistance of CMM by using fertilizers.
Abscisic Acid ; China ; Materia Medica ; Nitrogen ; Plant Growth Regulators

Objective To investigate the sexual behavior types, condom use and influencing factors of gonorrhea patients in Yunnan Province, and to provide evidence for the adjustment of sexually transmitted disease (STD) prevention and control strategy. Methods A cross-sectional study was carried out to investigate gonorrhea patients in 14 STD clinics in 7 more prevalent prefectures (cities) of Yunnan Province. A questionnaire survey was conducted to investigate the socio-demographic and sexual characteristics of the patients in a one-to-one way. Multiple Logistic regression model was used to analyze the influencing factors of sexual behavior. Results A total of 179 cases of gonorrhea were investigated. The average age was (29.01±8.93) years old. 95.53% (171/179) patients were 40 years old and 88.27% were male patients (158/179). Unmarried patients accounted for 55.31% (99/179). Service and self-employed patients accounted for 34.64% (62/179) and 23.46% (42/179) respectively. The rate of sexual intercourse with opposite sex was 98.32% (176/179), the rate of men who have sex with men was 1.68% (3/179) and the rate of having more than two sexual partners was 27.93% (50/179). The rate of sexual intercourse between temporary partners, spouses/fixed partners and commercial partners were 53.07% (95/179), 37.99% (68/179) and 8.94% (16/179) respectively. Recent sexual activity had lower condom use rate, 17.89% (17/95), 19.12% (13/68) and 18.75% (3/16) respectively. The main ways for gonorrhea patients to make temporary partners were friend introductions or gatherings, accounting for 66.32% (63/95). Condom use in male patients was worse than that in female patients (OR=0.234, 95% CI: 0.084-0.656, P=0.006). Conclusions The patients with gonorrhea were mainly unmarried young adults. The main risk behaviors were unprotected behaviors between heterosexual temporary and spouse/fixed sexual partners. The condom use consciousness was generally low. The promotion of safe sex education for young adults should be further strengthened, with special attention to the use of condoms for temporary sexual behavior and spouse/fixed sexual intercourse.

Aim To investigate the effects of Periplane-ta americana extract Ento-A on the immune function in immunosuppressed mice . Methods Immunosup-pressed mouse model was induced by intraperitoneal injection of cyclophosphamide in KM mice .To evalu-ate the effects of Ento-A on the immune function in im-munosuppressed mice , neutral red method and MTT assay were used respectively to detect the effects of En-to-A on the phagocytosis of peritoneal macrophages and T cell proliferation rate in mice; with sheep red blood cell as immunogen , the effects of Ento-A on the pro-duction of serum hemolysin were evaluated;peripheral blood was tested and immune organ index calculated . Results Compared with model control group , the high, medium and low doses of Ento-A could improve the expression of serum hemolysin in immunosup-pressed mice ( P<0.01 ) , and increase the spleen in-dex(P<0.01) and thymus index (P>0.05), signifi-cantly increased the content of WBC ( P<0.01 ) , PLT ( P<0.01 ) , HGB ( P<0.01 ) , while the contents of RBC was on the rise , with no significant difference ( P>0.05 ) in peripheral blood , significantly enhanced phagocytic function and T lymphocyte proliferative abil-ity in a dose-dependent manner ( P<0.01 ) .Conclu-sion Ento-A can enhance the immune function of im-munosuppressed mice .

Objective To evaluate the value of the electron bronchoscopy in diagnosis of carcinothoracic fluid in the case of replacing medical thoracoscopy and combining narrow-band imaging (NBI). Methods 89 cases of suspected cancerous pleural effusion patients, used electronic bronchoscope Olympus BF-1T 260 in place of medical thoracoscopy to enter pleural cavity in the usual way. First observed by white light bronchoscopy (WLB), then by narrow-band imaging (NBI) and take 5 pieces of tissue out respectively on the pleura of the lesion for pathological examination. Then compare the sensitivity and specificity of WLB and NBI methods, and the bleeding after biopsy. Result Among 89 cases of suspected cancerous pleural effusion patients, 85 cases found positive by white light bronchoscopy (WLB) , negative in 4 cases, 6 cases bleeding after biopsy (6.70%). Compared with the pathological results, WLB sensitivity 97.50%, specificity 22.22%. 68 cases found positive by NBI, negative 21 cases, no active bleeding after biopsy. Compared with the pathological results, the sensitivity of the NBI 86.67%, specificity 78.57%. Compared WLB with NBI, the former's sensitivity is superior to the latter, the latter's specificity is superior to the former. Both comparisons about sensitivity diagnosis of the and specificity are statistically significant (P < 0.05). Conclusion Electronic bronchial in place of medical thoracoscopy has high diagnostic rate in the carcinothoracic fluid, and the combination of NBI can improve the accuracy and security of the biopsy.

The contents of five heavy metals (Cu, Pb, As, Cd, Hg) in 17 batches of Cordyceps sinensis were determined by microwave digestion-ICP-MS, and their distribution in C. sinensis were analyzed. The results showed that the contents of Cu, Pb, Cd and Hg in all batches were in accordance with the international standards of Chinese Medicine-Chinese Herbal Medicine Heavy Metal Limit, with their contents in the stroma higher than that in the caterpillar body, and the excess rate of As, which mainly concentrated in the caterpillar body part of C. sinensis, was 88.24%, as the content of As in the caterpillar body was 7 to 12 fold of that in the stroma. In this study, the distribution of five heavy metals in C. sinensis was clarified, and the existing problems of arsenic limit of heavy metal in C. sinensis were analyzed, and some suggestions were put forward. It is hoped that the reference standard can be provided for the limited standard of arsenic in C. sinensis.

OBJECTIVEThis study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.

METHODSThe in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.

RESULTSR1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.

CONCLUSIONR1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.

Animals ; Blood Vessels ; pathology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Collagen ; pharmacology ; Disease Models, Animal ; Drug Combinations ; Ginsenosides ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; enzymology ; physiology ; Humans ; Laminin ; pharmacology ; Neovascularization, Physiologic ; drug effects ; Phosphatidylinositol 3-Kinases ; metabolism ; Protein Kinase Inhibitors ; pharmacology ; Proteoglycans ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Zebrafish