Potential of natural products containing 3-acyl tetramic acid as antibacterial precursors / 药学学报

The natural products containing 3-acyl tetramic acid units have a large number of complex and diverse structures, showing a variety of biological activities such as antibacterial, antiviral, anti-tumor and so on, especially antibacterial activity which are regarded as a potential reservoir of new antibiotics. In this paper, the antibacterial activities of various natural products containing 3-acyl tetramic acids and the new research hotspots and directions are reviewed.

Directed differentiation of human induced pluripotent stem cells into midbrain / 南方医科大学学报

OBJECTIVE@#To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro.@*METHODS@#hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment.@*RESULTS@#hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH+, FOXA2+ and Tuj1+ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection.@*CONCLUSION@#HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.

Clinical and genetic studies of two cases of fructose-1,6-bisphosphatase deficiency caused by FBP1 mutations / 中国实用儿科杂志

OBJECTIVE: To analyze the clinical and molecular genetic characteristics of 2 cases of fructose-1,6-bisphosphatase deficiency in the same family to provide evidence for the precise treatment,genetic counseling and prenatal diagnosis.METHODS: Clinical data were collected from 2 patients with hypoglycemia encephalopathy,and molecular genetic analysis was performed using targeted capture next-generation sequencing. RESULTS: The 2 patients were siblings,the male proband was 7 years old,mainly manifested with convulsions after hunger or ingestion of a large amount of fructose,accompanied by ketoacidosis;clinical diagnosis was hypoglycemia encephalopathy,and fructose metabolism abnormalities was suspected. The younger brother was 4 years old,mainly showing hunger and sweating in the morning,stomach ache after eating fruit,and convulsion episode once after hunger. Next-generation sequencing results showed that the siblings had c.333+1＿2 delinsTC and c.490 G>A compound heterozygous mutations in the FBP1 gene,and their parents were carriers with normal phenotype.The c.333+1＿2 delins TCis a novel mutation,c.490 G>A is a reported pathogenic mutation,and the two patients were diagnosed with fructose-1,6-bisphosphatase deficiency genetically. CONCLUSION: For children with unexplained hypoglycemia,convulsions and metabolic acidosis,the fructose-1,6-bisphosphatase deficiency should be considered. Early genetic analysis is helpful to clarify the cause,make precise treatment and improve prognosis.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome / 中华医学杂志(英文版)

<p><b>Background</b>Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.</p><p><b>Methods</b>A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.</p><p><b>Results</b>The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).</p><p><b>Conclusions</b>The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.</p>

Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2).</p><p><b>RESULTS</b>Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05).</p><p><b>CONCLUSIONS</b>Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.</p>

Clinical analysis of 96 patients with hypotonia cerebral palsy and their blood tandem mass spectrometry index / 中华神经医学杂志

Objective To explore the correlations of biochemical factors as gamma-aminobutyric acid (GABA) level with amino acid metabolism level in the blood, levels of intestinal immunoglobulin A (IgA)+complement factor 3 (C3), feeding intolerance and fatiguability in children with hypotonia cerebral palsy. Methods Ninety-six children with hypotonia cerebral palsy,admitted to our hospital from January 2009 to January 2012,were chosen in our study; questionnaire was used to understand the clinical symptoms of the children; the blood ammonia level,hepatic function and IgA+C3 level were obtained from routine blood chemistry testing, and amino acid metabolism was detected by blood tandem mass spectrometry; the correlations of GABA level with amino acid metabolism level in the blood, levels of IgA+C3, feeding intolerance and fatiguability were statistically analyzed. Results In all the 96 children with hypotonia cerebral palsy,63 (65.63％) had low arginine; 52 had both decreased arginine and elevated blood ammonia levels, enjoying negative correlation (r=-0.776,P=0.000); 42 had decreased arginine and reduced levels of IgA+C3 enjoying positive correlation (r=0.351,P=0.000); both decreased arginine level and feeding intolerance were noted in 47 with positive correlation (r=0.372,P=0.000).In these 96 children,30 (31.25％) had carnitine metabolism abnormality,including decreased propionyl carnitine/free carnitine or propionyl carnitine/acetylcarnitine levels in 21 (21.88％),increased hydroxyl palmitoyl carnitine/hydroxyl Palm enoyl carnitine level in 9 (9.37％),and decreased cysteine content in 3 (3.12％). Conclusion Metabolic abnormalities of arginine,carnitine and cysteine are noted in children with hypotonia cerebral palsy; a lot of exercise will consume arginine,carnitine and cysteine,which causes fatigue; children with low blood arginine content might also have increased blood ammonia level,reduced IgA+C3 level,trends of vomiting,susceptibility to infection and feeding difficulties,and therefore,children's mental state,immune function and exercise tolerance ability are affected.

Principles of Rehabilitation Treatment for the Cerebral Palsy Children Complicated with Epilepsy / 中国康复理论与实践

@#ObjectiveTo investigate advantage and disadvantage of different rehabilitation therapies used for cerebral palsy (CP) children complicated with epilepsy (EP).Methods140 CP children complicated with EP screened from 1402 CP cases, were analyzed for CP and EP types, MRI or CT, brain stem auditory evoked potentials (BAEP). All cases were treated with anti-epilepsy drugs (AEDs). Different rehabilitation therapies, including electrotherapeutic modalities, acupuncture, point injection, cerebroprotein hydrolysate injection, manual therapy, functional training, Chinese herb braising therapy, and cattle encephalon glycoside and ignotin injection were assessed.ResultsIn all 140 cases, a majority of EP types were myoclonic seizure and west syndrome, CP type was spasticity. Abnormality showed in MRI or CT (98%) and BAEP (90%). AEDs were effective for all 140 cases. Electrotherapeutic modalities, acupuncture, point injection, and cerebroprotein hydrolysate injection could make EP severely, but manual therapy, functional training, Chinese herb braising therapy, cattle encephalon glycoside and ignotin injection had no adverse effects on EP cases.ConclusionThe principles of rehabilitation treatment for the CP children complicated with EP are taking AEDs early and in a long term, avoiding electrotherapeutic modalities, acupuncture, point injection, and cerebroprotein hydrolysate injection, using manual therapy, functional training, Chinese herb braising therapy, and cattle encephalon glycoside and ignotin injection.