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Objective: Osteoporosis has become the biggest cause of non-fatal health issue. Currently, the limitations of traditional anti-osteoporosis drugs such as long-term ill-effects and drug resistance, have raised concerns toward complementary and alternative therapies, particularly herbal medicines and their natural active compounds. Thus, this study aimed to provide an integrative analysis of active chemicals, drug targets and interacting pathways of the herbs for osteoporosis treatment. Methods: Here, we introduced a systematic pharmacology model, combining the absorption, distribution, metabolism, and excretion (ADME) screening model, drug targeting and network pharmacology, to probe into the therapeutic mechanisms of herbs in osteoporosis. Results: We obtained 86 natural compounds with favorable pharmacokinetic profiles and their 58 targets from seven osteoporosis-related herbs. Network analysis revealed that they probably synergistically work through multiple mechanisms, such as suppressing inflammatory response, maintaining bone metabolism or improving organism immunity, to benefit patients with osteoporosis. Furthermore, experimental results showed that all the five compounds (calycosin, asperosaponin VI, hederagenin, betulinic acid and luteolin) enhanced osteoblast proliferation and differentiation in vitro, which corroborated the validity of this system pharmacology approach. Notably, gentisin and aureusidin among the identified compounds were first predicted to be associated with osteoporosis. Conclusion: Herbs and their natural compounds, being characterized as the classical combination therapies, might be engaged in multiple mechanisms to coordinately improve the osteoporosis symptoms. This work may contribute to offer novel strategies and clues for the therapy and drug discovery of osteoporosis and other complex diseases.
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Lorlatinib (PF-06463922) is a highly selective and potent third generation anaplastic lymphoma kinase (ALK) inhibitor with dual activity against c-ros oncogene 1, a receptor tyrosine kinase (ROS1). In November 2018, the US Food and Drug Administration approved lorlatinib for treatment of disease progression in ALK-positive and late-stage NSCLC patients who receive the treatment with crizotinib and at least one of other ALK inhibitors; and those with disease progression after treatment of alectinib or ceritinib as the first ALK inhibitor. The results of phase I/II clinical trials showed that it has effective initial anti-tumor activity, strong intracranial therapeutic activity, with less tolerance and safety issues. This paper systematically reviewed the chemical structure, mechanism of action, pharmacodynamics, pharmacokinetics, usage and dosage, clinical research, safety and upcoming research fields of lolatinib, to provide an update on clinical or laboratory research and clinical practice.
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@# Objective Toinvestigatetheclinicalfeaturesofneonatesandmothersonthescreeningofcongenital hypothyroidism(CH),andtoprovideabasisforavoidingthemisseddiagnosisofCH.Methods Atotalof206neonateswith positive thyroid stimulating hormone (TSH) screening were collected from January 2016 to November 2017, and 206 neonateswithnegativeTSHwererandomlyselectedoverthesameperiodasnormalcontrolgroupaccordingto1∶1ratio.The impactofneonatalsex,gestationalage,bodyweightandmaternalcomorbidityonCHscreeninganddiagnosiswasanalyzed inthetwogroups.Results ThebodyweightofneonateswithpositiveTSHscreeningwaslowerthanthatofnormalnewborn infants(P＜0.05),whiletherewerenosignificantdifferencesinsex,gestationalage,theproportionofpreterm,matureand post-termdeliverybetweentwogroups.ComparedwithnormalTSHscreening,theproportionofmotherwithhypothyroidism andTSHlevelwassignificantlyhigherinscreeningpositivegroup,butFT3andFT4levelswerelower(P＜0.05).Therewere no significant differences in the ratio of gestational diabetes mellitus, anemia, subclinical hypothyroidism and hyperthyroidism,hemoglobinandfastingglucosebetweenthetwogroupsofmothers.Comparedwithconfirmednormalgroup (n=198),thebodyweightwaslowerinconfirmedCHgroup(n=8),andtheproportionofmotherwithhypothyroidismandTSH levelwassignificantlyhigherinconfirmedCHgroup,FT3andFT4levelswerelower(P＜0.05).Therewerenosignificant differences in sex, gestational age, the ratio of subclinical hypothyroidism and hyperthyroidism between CH group and confirmed normal group. Conclusion Neonatal low body weight and maternal hypothyroidism significantly affect the screening and diagnosis of CH. Special attention should be paid to clinical screening of CH in order to avoid missed diagnosis.
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Objective To assess the value of ultrasound examination in transvaginal diagnosis of normal fetal heart with 11-14 weeks of gestation.Methods Totally 158 cases of normal fetal heart with high risk pregnancy and nuchal translucency thickness were examined by two ultrasoud approaches:transvaginal(TVS) and tranabdomina(TAS) in 11-14 weeks of gestation.Results The group of TVS was obviously clearer than TAS by displaying the normal fetal cardiac structural in 12 week of gestation and 13-14 weeks of gestation with significant difference between the two groups (P<0.05),respectively.No significant difference between the two groups in 11 week of gestation was observed.Conclusion The transvaginal echocardiogram is of clinical value in the high risk gravida during the late first and the early second trimester.
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Iliac artery rupture is a rare complication of post-stenting angioplasty and can lead to massive life-threatening haemorrhage. Conventional surgery can not repair the damaged vessel easily and may cause substantial blood loss and high operative morbidity and mortality. We report our experience with a self-expanding covered endoprosthesis for endovascular repair of the rupture of an iliac artery caused by stenting angioplasty.
Subject(s)
Aged, 80 and over , Female , Humans , Angioplasty , Blood Vessel Prosthesis Implantation , Endarterectomy , Iliac Artery , Wounds and Injuries , Rupture , StentsABSTRACT
<p><b>BACKGROUND</b>Foetal echocardiography has become a diagnostic method to detect foetal congenital heart disease with high probability. However, it is not only time consuming and but also difficult to visualize outflow tract of foetus early in the second trimester of pregnancy, even for an experienced obstetric ultrasonographer. Recently, many methods for screening foetal cardiac anomalies were explored, but much more work is needed to develop an effective and suitable screening method. The aim of this study was to investigate the clinical significance of utilising the ductus venosus (DV) Doppler examination and the four-chamber view of heart to screen for foetal cardiac malformation in early second trimester of pregnancy.</p><p><b>METHODS</b>Heart and DV of 401 consecutive foetuses in early second trimester (12(+1) - 17(+6) weeks) in high risk pregnancies were examined with Acuson 128 xp/10 or Sequoia 512 ultrasound diagnostic systems. Absent or reversed flow during atrial contraction (A-wave) in the DV was defined as sufficiently abnormal to screen for foetal cardiac malformations. The foetal echocardiographic diagnosis was confirmed by postnatal echocardiography (or postmortem). The sensitivities of screening tests were compared among the three methods: DV Doppler examination, four-chamber view alone, and the combination of both techniques.</p><p><b>RESULTS</b>Satisfactory examinations were obtained in 383/401 foetuses (95%). Thirty foetuses with cardiac abnormalities were confirmed by neonatal echocardiography (or postmortem). The sensitivity of DV Doppler examination or four-chamber view alone is 63% (19/30) and 60% (18/30), respectively. The sensitivity of combining information, DV Doppler flow waveform and four-chamber view, to screen for foetal cardiac malformation is 83% (25/30) and significantly better than that of either DV Doppler flow waveform or four chamber view alone (P < 0.05).</p><p><b>CONCLUSION</b>Doppler flow waveform of DV can be used to screen for foetal cardiac malformation early in the second trimester. Combining information from Doppler flow waveform of DV and four-chamber view will improve the overall sensitivity of the screening.</p>