Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3～9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective:To explore the mechanism of bone morphogenetic protein 2 (BMP-2) regulating pulmonary vascular remodeling in pulmonary hypertension (PH).Methods:Pulmonary artery smooth muscle cells (PASMC) groups: control group, PH group, PH+BMP-2 group, PH+BMP-2+ small interfering BMP receptor(si-BMPR)-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group. In vitro PH model was induced by hypoxia. The three BMP-2 receptors were silenced by the transfection of si-BMPR-Ⅰa, si-BMPR-Ⅰb and si-BMPR-Ⅱ plasmids, respectively. Cell proliferation and apoptosis in each group were detected, transient receptor potential ion channel C1/6 (TRPC1/6), p21 mRNA and protein levels, and intracellular Ca 2+ concentration were detected. Results:The intracellular Ca 2+ concentration in the PH group was higher than that in the control group: (785.15 ± 44.26) nmol/L vs. (224.15 ± 15.87) nmol/L, the and apoptosis rate was lower than that in the control group: (3.15 ± 0.22)% vs. (7.31 ± 0.45)%, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2 group was (297.64 ± 21.46) nmol/L, and was lower than that in the PH group, and apoptosis rate was (6.88 ± 0.75)%, and was higher than that in the PH group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP-2+si-BMPR-Ⅰa group, PH+BMP-2+ si-BMPR-Ⅰb group, PH+BMP -2+si-BMPR-Ⅱ group was (412.31 ± 29.57), (384.34 ± 30.66), (695.23 ± 39.85) nmol/L, and was higher than that in the PH+BMP-2 group, and apoptosis rate was (4.10 ± 0.27)%, (4.26 ± 0.28)%, (3.33 ± 0.24)%, and was lower than that in the PH+BMP-2 group, there were statistical differences ( P<0.05). The intracellular Ca 2+ concentration in the PH+BMP -2+si-BMPR-Ⅱ group was higher than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, the apoptosis rate was lower than that in the PH+BMP-2+si-BMPR-Ⅰa group and PH+BMP-2+ si-BMPR-Ⅰb group, there were statistical differences ( P<0.05). Conclusions:BMP-2 mainly inhibits the expression of TRPC1/6 by interacting with the receptor BMPR-Ⅱ, inhibits the influx of Ca 2+ and promotes the expression of p21, thereby inhibiting the proliferation of PASMC and promoting apoptosis, participating in pulmonary vascular remodeling in PH.

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Objective : To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) oparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) . Methods : Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot. Results FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.

Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.
Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Conservation of Natural Resources ; Sustainable Development ; Internationality ; China

Objective : To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) nanomaterials (FA⁃TPGS) , which can stably load and effectively release siRNA , and to observe the effects of nanoparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) . Methods : Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot. Results : FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.