A new class of potent liver injury protective compounds: Structural elucidation, total synthesis and bioactivity study

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Enantiomeric pairs of meroterpenoids from Rhododendron fastigiatum / 中国天然药物

Five pairs of optically pure meroterpenoid enantiomers (1a/1b-5a/5b) and two known compounds (6 and 7) were isolated from Rhododendron fastigiatum. Compounds 1a/1b-5a/5b were resolved from naturally scalemic mixtures by chiral HPLC. Their structures were elucidated by spectroscopic methods, X-ray crystallographic experiments, and ECD analyses. Compounds 1a/1b, 2a/2b, 3b, 4a/4b, and 5a/5b were new meroterpenoids with different polycyclic systems. Two enantiomeric pairs (2a/2b and 3a/3b), 6, and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) in vitro.

Flavonoids with PTP1B inhibition from Broussonetia papyrifera / 中国中药杂志

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) μmol·L-1.

Clinical Value of Pulmonary Artery Parameters and Pulmonary Valve Annulus Z Scores for Choosing the Type of Operation in Complete Repaire of Pediatric Tetralogy of Fallot / 中国循环杂志

Objective: To investigate the clinical value of transthoracic echocardiography (TTE) measured pulmonary artery parameters and pulmonary valve annulus Z scores for choosing the type of operation in complete repair of pediatric tetralogy of Fallot (TOF) Methods: A total of 143 patients received complete repair of pediatric TOF in our hospital were retrospectively studied. The patient's median age was 8 (1-171) months. Based on the type of operation, patients were divided into 2 groups: Trans-annular patch group, n=100 and Valve sparing repair group, n=43. Conventional TTE parameters, right ventricular outflow parameters and pulmonary valve annulus Z scores were compared between 2 groups; pulmonary valve annulus diameters measured by TTE and surgery were studied by correlation analysis. Results: Compared with Valve sparing repair group, Trans-annular patch group had decreased left ventricular end diastolic diameter (23.14±3.82) mm vs (25.23±4.56) mm, pulmonary valve annulus diameter (8.52±2.18) mm vs (10.01±2.61) mm and main pulmonary artery diameter (67.31 vs 82.91) all P<0.05. With reduced value of pulmonary valve annulus Z scores, the constituent ratio in Trans-annular patch group was gradually increasing and in Valve sparing repair group was gradually decreasing, all P<0.05. Correlation analysis indicated that pulmonary valve diameters measured by TTE and surgery had moderate agreement (r=0.581, P<0.001). Conclusion: TTE measured pulmonary valve annulus diameter, main pulmonary artery diameter and pulmonary valve annulus Z scores were the objective parameters provided to surgeon at pre-operation, which had clear clinical value.

Activating blood circulation to remove stasis treatment of hypertensive intracerebral hemorrhage: A multi-center prospective randomized open-label blinded-endpoint trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH).</p><p><b>METHODS</b>This was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded.</p><p><b>RESULTS</b>After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups (P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group (P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 (P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment (P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment (P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group.</p><p><b>CONCLUSION</b>The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.</p>

Lung ultrasound for diagnosis of neonatal atelectasis / 中华儿科杂志

<p><b>OBJECTIVE</b>The diagnosis of neonatal atelectasis (NA) is usually based on clinical manifestations and chest X-rays, lung ultrasounds are not included in the diagnostic work-up of NA.Recently, ultrasounds have been used extensively and successfully in the diagnosis of many kinds of lung diseases, but few studies have addressed NA. The aim of this study was to evaluate the ultrasound imaging features of NA-and to evaluate the value of lung ultrasound in diagnosing NA.</p><p><b>METHOD</b>From May, 2012 to June, 2013, 40 newborn infants with NA and another 40 neonates without lung disease were enrolled into this study.Lung ultrasound was performed at the bedside by a single expert physician.In a quiet state, the infants were positioned in supine, side or prone postures. The lung field was divided into three areas by the anterior auxilary and posterior auxilary line. The regions of the bilateral lungs were scanned by the probe which was vertical or parallel with the ribs, then compared the results with conventional chest X-ray findings.</p><p><b>RESULT</b>(1) The main ultrasound imaging features of neonatal NA include lung consolidation with air bronchograms, pleural line abnormalities and A-line disappearance. Besides, lung pulse and lung sliding disappearance could be seen by real-time ultrasound. (2) The sensitivity of lung ultrasound for diagnosis of NA was 100%, while it was only 70% for conventional chest X-rays.</p><p><b>CONCLUSION</b>Use of ultrasound to diagnose NA is accurate and reliable, the sensitivity was superior to that of conventional chest X-ray examination, which also has many other advantages including easy-operating, non-ionizing, can be performed at the bedside, therefore, ultrasonic can provide important value for clinicians.</p>

Clinical characteristics, diagnosis and management of respiratory distress syndrome in full-term neonates / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Respiratory distress syndrome (RDS) is one of the most common causes of neonatal respiratory failure and neonatal death, however, its clinical characteristics are very different from premature RDS, and these characteristics have not been well documented as yet. This study was to investigate the pathogenesis, clinical characteristics and management strategies of RDS in full-term neonates, with the aim of developing a working protocol for improving the outcome in full-term neonates with RDS.</p><p><b>METHODS</b>A total of 125 full-term infants with RDS were enrolled in this study. Their clinical and laboratory data were collected for analyzing the characteristics of full-term neonatal RDS.</p><p><b>RESULTS</b>(1) The 125 cases included 94 male and 31 female infants, vaginal delivery occurred in 80 cases and cesarean section in 45 cases. (2) The onset time of RDS was (3.11 ± 3.59) hours after birth. (3) The possible reasons included severe perinatal infections in 63 patients, elective cesarean section in 34 cases, severe birth asphyxia in 12 patients, meconium aspiration syndrome in 9 patients, pulmonary hemorrhage in 4 patients and maternal diabetes in 3 patients. (4) Complications included multiple organ system failure (MOSF) in 49 patients, persistent pulmonary hypertension of newborn (PPHN) in 25 patients, acute renal failure in 18 patients, severe hyperkalemia in 25 patients, severe metabolic acidosis in 6 cases, severe myocardial injury in 9 cases, pulmonary hemorrhage in 3 cases, disseminated intravascular coagulation in 14 patients and shock in 12 patients. (5) Four patients died, the mortality was therefore 3.2% with the main cause of septicemia complicating of MOSF, but their prognosis was improved while comprehensive treatment measures including early mechanical ventilation and broad spectrum antibiotics were taken into account.</p><p><b>CONCLUSIONS</b>RDS is not an uncommon disease in full-term infants and is associated with a higher mortality, its clinical characteristics are very different from premature RDS, and its onset is earlier and is more likely to develop into PPHN and/or MOSF. The main cause of death is severe infection complicating of MOSF and most patients require prolonged mechanical ventilation. Comprehensive management strategies will help to improve patient's prognosis.</p>

Synthesis and AchE inhibitory activity of 2-phenoxy-indan-1-one derivatives / 药学学报

<p><b>AIM</b>To design and synthesize novel AchE inhibitors.</p><p><b>METHODS</b>The condensation of 2-bromo-5, 6-dimethoxy-indan-1-one with various aminoalkyl phenols in the presence of K2CO3 and acetonitrile gave the corresponding title compounds, and the in vitro AchE and BchE inhibitory activities were evaluated by the modified Ellman method.</p><p><b>RESULTS</b>Sixteen novel target compounds 8a - p were synthesized, their structures were confirmed by 1H NMR, MS, IR and elemental analysis. Preliminary pharmacological test demonstrated that most of these compounds displayed high AchE inhibitory activities, the IC50 of the most potent inhibitor 8h was 50.0 nmol x L(-1), similar to that of Huperzine A (IC50 = 53.0 nmol x L(-1)), while all the compounds were almost inactive against BchE.</p><p><b>CONCLUSION</b>2-Phenoxy-indan-1-one derivatives exhibit high activities of AchE inhibition and are worthy of further investigation.</p>