One case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency and literature review / 中国基层医药

Objective:To summarize the clinical phenotype and genetic characteristics of one child patient with mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mHS) caused by HMGCS2 gene mutation. Methods:One child patient with mHS who received treatment in Chongqing University Three Gorges Hospital on April 10, 2020 was included in this patient. The child was hospitalized due to cough, shortness of breath and deep coma. After admission, gas chromatography-mass spectrometry of the blood and urine samples and high-throughput whole genome sequencing were performed. The pedigree of the child with gene mutation was analyzed. The child was diagnosed with mHS. Related publications published by June, 2020 were searched in Wanfang database, Chinese Journal Full Text Database, PubMed and HGMD databases using search terms "mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency", "HMGCS2" "mHS deficiency". Forty-three papers addressing mHS deficiency were retrieved. The clinical phenotype and genotypes of the child with HMGCS2 mutation were summarized. Results:As of June 2020, there were 44 children with mHS deficiency, including the child reported in this study. These children consisted of 15 males, 11 females and 18 unknown genders. Among these children, 29 were aged 0-24 months, 4 were aged > 24 months, 6 had no symptoms, and 5 were of unknown age of disease onset. The first symptoms of most children were fever, cough, acute gastroenteritis, and coma. Twenty-seven children had hypoglycemia, 21 children had metabolic acidosis, 15 children developed hepatomegaly, 16 children had increased FFA/D-3-HB, and 10 children were tested 4-hydroxy-6-methyl-2-pyrone positive. The child included in this study had hepatomegaly, elevated alanine aminotransferase and metabolic acidosis. Gas chromatography-mass spectrometry results showed that a variety of metabolites were increased. Tandem mass spectrometry results showed that C40 level was elevated, and long-chain carnitine contents were increased. High-throughput whole genome sequencing results revealed that there were two heterozygous mutations in HMGCS2 gene, (NM_0055) c.559+1G > A; c. 758 T > C heterozygous mutation. Sanger sequencing and parental origin analysis showed that the mutations in this child were from parents. The two gene mutations in this child were new mutations, which have not been reported in China and countries outside China. According to the criteria and guidelines for interpretation of ACMG sequence variation, the variation was determined to be pathogenic. Conclusion:When a child has hypoketotic hypoglycemia and/or metabolic acidosis, increased FFA/D-3-HB and acetylcarnitine levels, mHS deficiency should be considered. HMGCS2 gene examination can help diagnose mHS deficiency.

Evodiamine inhibits growth of Huh7 cells and enhances their sensitivity to TRAIL / 中国病理生理杂志

AIM:To investigate the effects of evodiamine on the growth and apoptosis of human hepatocellular carcinoma Huh7 cells,and to illustrate the molecular mechanism that evodiamine enhances antitumor activity of tumors nec -rosis factor-related apoptosis-inducing ligand(TRAIL)in Huh7 cells.METHODS: The cell viability was measured by MTT assay.The cell cycle distribution was analyzed by flow cytometry.The apoptosis rate was determined by TUNEL stai-ning.The protein levels of cell cycle-and apoptosis-related proteins were detected by Western blot analysis.RESULTS:Treatment of Huh7 cells with evodiamine reduced the cell viability(P<0.05).Evodiamine induced cell cycle arrest in G2/M phase by upregulation of p27,cyclin B1, cell division cycle protein 2(Cdc2)and p-Cdc2.Evodiamine triggered apoptosis accompanied by cleavage of caspase-3 and poly(ADP-ribose)polymerase(PARP).Combination of evodiamine with TRAIL significantly reduced the cell viability and increased cleavage of caspase -3 and PARP as compared with the use of each agent alone.Moreover,evodiamine increased the expression of death receptor 5(DR5)in the Huh7 cells.CON-CLUSION:Evodiamine inhibits the cell growth by reducing the cell viability and inducing cell cycle arrest.Evodiamine also triggers cell apoptosis and enhances the sensitivity of Huh 7 cells to TRAIL by upregulating the expression of DR5.

Novel PHEX gene mutations in patients with X-linked hypophosphatemic rickets: an analysis of 2 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families.</p><p><b>RESULTS</b>Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c.931dupC, which caused early termination of translation and produced the truncated protein p.Gln311Profs*13; the other patient had a splice site mutation, IVS14+1G>A, which caused the skipping of exon 15 and produced an incomplete amino acid chain. Their parents had normal gene phenotypes.</p><p><b>CONCLUSIONS</b>c.931dupC and IVS14+1G>A are two novel mutations of the PHEX gene and might be the new pathogenic mutations of XLH.</p>

NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell death in non-small cell lung cancer cells / 中国天然药物

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and β-lapachone (β-lap) induced a rapid depletion of NAD(+) pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or β-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD(+), repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer.

Correlation analysis between the status of DBCD donors and postoperative recovery of organ function in organ transplant recipients / 器官移植

Objective To analyze the correlation between the status of the donation after brain and cardiac death (DBCD)donors and postoperative recovery of the organ function in the liver and renal transplant recipients.Methods The assessment data and organ protection measures of 12 DBCD donors admitted to the Organ Transplantation Center in Sichuan Provincial People’s Hospital from August 2011 to November 2013 were retrospectively analyzed.The parameters of postoperative recovery of 12 liver and 22 renal transplant recipients were also assessed.The correlation between the parameters of the donors and postoperative recovery of the liver and renal transplant recipients was statistically analyzed.Results Among 12 liver transplant recipients,1 patient had primary non-function (PNF)(1 /12,8%)and 11 cases developed delayed graft function (DGF) after renal transplantation (11 /22,50%).Intensive care unit (ICU)period,liver function,maintaining systolic blood pressure (SBP),blood coagulation function,blood glucose level and electrolyte (Na +/K +) were significantly correlated with postoperative recovery of the liver and kidney function in the recipients (all in P <0.05 ).Age,cause of brain death,maintaining diastolic blood pressure (DBP),activated partial thromboplastin time (APTT)and pH of arterial blood gas (ABG)were associated with postoperative recovery of the liver function.Total bilirubin and white blood cell count (WBC)were correlated with postoperative recovery of kidney function.Conclusions DBCD donors cater to the specific conditions in China.The incidence of postoperative PNF in liver recipients is relatively low whereas and the incidence of DGF after renal transplantation is relatively high.Assessment of the DBCD donors and organ protection measures should be specifically taken to enhance the clinical efficacy of liver and renal transplantation from DBCD donors.

Effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients-a prospective, randomized, controlled study / 中华器官移植杂志

Objective To evaluate the effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients.Methods Between March 2007 and March 2011,a total of 60 patients undergoing consecutive kidney transplantation with asymptomatic arteriovenous fistula were divided randomly into two groups: arteriovenous fistula closure group,and non-arteriovenous fistula closure group.By using echocardiography,the changes in CO,CI,EF,LVEDV and LVMI were analyzed.Results At 12th month after transplantation,the values of CO,LVEDV and LVMI were significantly lower than those before transplantation (P＜0.05).The value of CI also showed a tendency to decrease (P＞0.05),and the value of EF was increased significantly (P＜0.05).At 6th month after arteriovenous fistula closure (18 months after transplantation),the values of CO,CI,LVEDV and LVMI were significantly lower than those before arteriovenous fistula closure (12 months after transplantation) (P＜0.05),and the value of EF was increased significantly (P＜0.05),but the values of CO,CI,EF,LVEDV and LVMI remained unc(b)anged in controls (P＞0.05).At 18th month after transplantation,the values of CO (4.4 ±0.8 L/min),CI [3.0 ± 0.8 L·min-1·m-2],LVEDV (110.0 ± 17.4 ml) and LVMI (114.7 ± 42.5g/m2) in trial group were significantly lower than the values [CO: 5.1 ± 0.9 L/min,CI: 3.5 ± 1.0L·min-1·m-2,LVEDV: 121.4±19.3 mL,LVMI: 138.4±44.1 g/m2] in controls (P＜0.05),and the value of EF (75.2％ ± 7.4％ vs.70.5％ ± 8.2％) significantly higher (P＜005).Conclusion In both groups,kidney transplantation benefits significantly the regression of cardiac mass,cardiac index and left ventricular dimensions,but closure of asymptomatic AVF induces more significant regression.

Effects of mesenchymal stem cells transplantation on cranial suture distraction osteogenesis in growing goats / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To observe the effects of mesenchymal stem cells (MSCs)on cranial suture under mechanical strain in growing goats.</p><p><b>METHODS</b>10 growing goats were used in this study. A customized distractor was used for distraction of the coronal suture at a rate of 0.4 mm/day for 8 days. The experimental group(5 goats) was injected with autologous MSCs into the distracted region, whereas the control group (5 goats) with injection of physiological saline. All animals were killed at 4 weeks after the end of distraction. Scanning electron microscopy and histological analysis were taken to observe the samples.</p><p><b>RESULTS</b>4 weeks after the end of distraction, the cranial sutures in all animals were separated successfully. The new bone formation at the edge of suture in the experimental group was superior to that in the control group.</p><p><b>CONCLUSION</b>Autologous MSCs transplantation may promote the cranial suture distraction osteogenesis in the growing goats.</p>

Preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release / 中国中药杂志

<p><b>OBJECTIVE</b>To study the preparation of solid lipid nanoparticles loaded with Xionggui powder-supercritical carbon dioxide fluid extraction and their evaluation in vitro release.</p><p><b>METHOD</b>To prepare solid lipid nanoparticles (SLN) loaded with Xionggui powder-supercritical carbon dioxide fluid extraction (XG-CO2-SFE) using a hot dispersion- ultrasonic technique, establishing the best prescription of XG-CO2-SFE-SLN through orthogonal design methods using entrapment efficiency of nanoparticles as index, and investigating their physicochemical characterizations. The invro release action of SLN was studied in different dissolution mediums using dynamic dialyse method.</p><p><b>RESULT</b>The best prescription was: phospholipid: F-68: stearie acid glyceride = 5: 2 : 1, the entrapment efficiency of nanoparticles was 96.3%, and the results revealed the nanoparticles were sphere like with the mean size of 245.8 nm, the mean Zeta potential was -33.5 mV. The in vitro release meet to Weibull distribution in physiological brine and to single-index model in pH 7.4 phosphate liquid (40% EtOH).</p><p><b>CONCLUSION</b>The preparation method of the XG-CO2-SFE-SLN was appropriate, and the XG-CO2-SFE-SLN was released completely.</p>

Advances of studies on dropping pills / 中国中药杂志

From the characteristic, prepare the craft, quality control, bioavailability and clinical curative effect,etc. To do the summary to the modern research of dropping pill, analyse and is thought to dropping pill that has wide development prospects.

Studies on preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex / 中国中药杂志

<p><b>OBJECTIVE</b>To find the best condition of the preparation technology of Flos Magnoliae essential oil-beta-cyclodextrin inclusion complex.</p><p><b>METHOD</b>L9(3(4)) table was used to examine the effects of 4 factors, and the inclusion rate of each test was determined of orthogonal test.</p><p><b>RESULT</b>The best condition was:oil:beta-cyclodextrin:water = 1:8:60 (mL:g:mL), stirring for 1 hour at 80 degrees C.</p><p><b>CONCLUSION</b>The complex prepared on the condition aforementioned is stable and stirring has a highest inclusion rate.</p>

Study on in vitro dissolution rate of geniposide in huangqin qingfei dispersible tablet / 中国中药杂志

<p><b>OBJECTIVE</b>To study in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet.</p><p><b>METHOD</b>A reversed-phase HPLC method was developed for determination of geniposide. In vitro dissolution rates were compared between Huangqin Qingfei dispersible tablet and conventional tablet in the dissolution medium of pH 1.0, 2.85, 4.5, 6.8, and 8.0 accordingly. Zero-class model, single-index model, logarithm normal school model, and Weibull distributing model were used to simulate the dissolution curve.</p><p><b>RESULT</b>The dissolution rate of two tablets is not affected by pH so much, and they can dissolve within 5 to 10 minutes. Weibull distributing model is the best simulation for in vitro dissolution. Comparing with conventional tablet, dispersible tablet dissolve quickly and completely.</p><p><b>CONCLUSION</b>The in vitro dissolution rate of geniposide in Huangqin Qingfei dispersible tablet conforms to Weibull distributing model. The dispersible tablet is able to release rapidly.</p>

Comparative studies on isolation and purification of Chinese medicine decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate different methods by treating water-decocted liquid of 6 Chinese medical herbs and 4 co-prescription respectively with alcohol, ultrafilter, macroporousresin and clarifier.</p><p><b>METHOD</b>The contents of target component in those extracts were determined with HPLC or titration, and quantitative and qualitative determination of the impurity components, such as polysaccharide and protein, was made.</p><p><b>RESULT</b>Each method showed its advantages and disavantages.</p><p><b>CONCLUSION</b>Different method can be chosen according to the clinical and preparation demands or the characteristic of components.</p>