Observation on the efficacy of moderate and high myopia patients with vault greater than 1 000 μm after implantation of phakic posterior chamber implantable contact lens / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the efficacy of moderate and high myopia patients with vault greater than 1 000μm after implantation of phakic posterior chamber implantable contact lens(ICL).METHODS: A total of 42 patients(73 eyes)who received ICL implantation in the hospital and had postoperative vault greater than 1 000 μm between January 2014 and January 2017 were selected and retrospectively studied. Changes in visual acuity, intraocular pressure, corneal endothelial cell density, anterior chamber-related parameters(chamber angle, central anterior chamber depth, anterior chamber volume)and vault were compared among patients before surgery, at 1, 3, 6mo and 1a after surgery and at the last follow-up.RESULTS: The uncorrected visual acuity(UCVA)at 1, 3, 6mo and 1a after surgery and at the last follow-up was better than that before surgery(all P<0.05), and the chamber angle, central anterior chamber depth and anterior chamber volume were smaller or lower than those before surgery(all P<0.05), but there were no statistical differences in UCVA, chamber angle, central anterior chamber depth and anterior chamber volume at each time point after surgery(all P>0.05). The intraocular pressure at 1mo after surgery was lower than that before surgery(P<0.05), but the intraocular pressure at 3, 6mo and 1a after surgery and at the last follow-up was not statistically different from that before surgery(all P>0.05). There was no statistical significance in the corneal endothelial cell density at 1, 3, 6mo and 1a after surgery and at the last follow-up compared with that before surgery(all P>0.05). The vault at 1, 3, 6mo and 1a after surgery and at the last follow-up showed a decreasing trend, and the difference was statistically significant at each time point after surgery(all P<0.05).CONCLUSION: The short-term and long-term efficacy are better in moderate and high myopia patients with vault greater than 1 000 μm after ICL implantation, and there are no significant effects on the intraocular pressure and corneal endothelial cell. The postoperative anterior chamber structure is relatively stable and the vault tends to decrease over time. In most cases, close observation is sufficient and intraocular lens replacement is generally not required.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

DHX37 gene heterozygous variant—a frequent cause of embryonic testicular regression syndrome / 中华内分泌代谢杂志

Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.

Effect of total body 137Cs γ-irradiation on the m 6A modification profile of circRNA in mouse bone marrow cells / 中华放射医学与防护杂志

Objective:To investigate the effect of ionizing radiation on the N 6-methyladenine (m 6A) modification profile of circular RNA (circRNA) in mouse bone marrow cells and provide scientific basis for revealing the relationship between RNA epigenetic modification and hematopoietic radiation injury. Methods:A total of twenty four C57BL/6 J mice were randomly divided into two groups: the healthy control group ( n=12), and ionizing radiation group ( n=12) irradiated in total body with 4 Gy of 137Cs γ-rays. At 5 min after irradiation, mice were killed and bone marrow cells were collected from the femur. Total RNAs were extracted and the changes in circRNA m6A modification profiles were investigated by RNA immunoprecipitation-high-throughput sequencing (MeRIP-Seq) technology and bioinformatics analysis. The representative alterations of m 6A peaks were validated by MeRIP-PCR assay. Results:325 and 455 m 6A sites were identified on circRNAs in the healthy control group and ionizing radiation group (178 common sites, 147 specific sites in the healthy control group and 277 specific sites in ionizing radiation group), respectively. 1 275 and 1 017 deriving genes of m 6A-circRNAs were identified in the healthy control group and ionizing radiation group (767 common genes, 508 specific genes in the healthy control group and 250 specific genes in ionizing radiation group), respectively. Compared with the control healthy group, 414 (178) m 6A peaks was significantly up- (down-) regulated in the ionizing radiation group( P < 10 -10; fold-change cut-off > 5). Moreover, Gene Ontology (GO) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups involves various functions including chromatin regulation, ciliary transition fiber and poly (A)-specific ribonuclease activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) assay revealed that the deriving genes of circRNAs with differentially methylated m 6A sites between two groups included numerous pathways such as platelet activation, Fc γ R-mediated phagocytosis and B cell receptor signaling pathway. Conclusions:Ionizing radiation triggers rapid alterations in the m 6A modification profile of circRNA in mouse bone marrow cells. The deriving genes of differentially methylated circRNAs are associated with a variety of functions and signaling pathways of hematopoietic radiobiology.

Analysis on the relationship between pulmonary tuberculosis and vitamin D in Qinghai Province / 中华传染病杂志

Objective:To investigate the vitamin D level of pulmonary tuberculosis patients in Qinghai Province, and to explore the correlation between vitamin D level and pulmonary tuberculosis.Methods:From May to September 2020, 208 bacterial confirmed pulmonary tuberculosis patients who were admitted to The 4th People′s Hospital of Qinghai Province were enrolled as the pulmonary tuberculosis group, and 129 healthy people who underwent physical examination during the same period were enrolled as the healthy control group. Independent sample t test and chi-square test were used for statistical analysis. Results:The deficiency rate of vitamin D was 11.06%(23/208) in the pulmonary tuberculosis group, which was higher than that (3.10%(4/129)) in the healthy control group, and the difference was statistically significant ( χ2=6.840, P=0.009). The vitamin D level was (56.84±20.03) μg/L in the pulmonary tuberculosis group, which was lower than that ((67.39±17.07) μg/L) in the healthy control group, and the difference was statistically significant ( t=5.154, P<0.01). The vitamin D levels were not different between the newly treated ((56.66±20.02) μg/L)) and retreated pulmonary tuberculosis patients ((59.11±20.81) μg/L) ( t=0.468, P=0.650). The vitamin D level of simple pulmonary tuberculosis patients ((57.82±20.01) μg/L) was higher than that of pulmonary tuberculosis patients combined with other diseases ((48.08±18.46) μg/L), and the difference was statistically significant ( t=2.132, P=0.034). Conclusion:Pulmonary tuberculosis is associated with decreased vitamin D levels, and patients with pulmonary tuberculosis are more likely to suffer from decreased or deficient vitamin D, which suggests clinicians considering the vitamin D status when treating pulmonary tuberculosis patients.

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol- containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

Development and Revision of Dosage Forms General Chapters of Chinese Pharmacopeia 2020 Edition Volume / 中国药学杂志

OBJECTIVE: To guide pharmaceutical manufacturing to pay full attention to and implement the quality control and overall requirements of preparation production based on the analysis of the revision work and major changes of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. METHODSE: This article mainly introduces the compilation progress of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. RESULTS: The analysis is helpful to improve the integrity, advancement and readability of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia. CONCLUSION: The improvement of the Dosage Forms General Chapters of the 2020 edition of the Chinese Pharmacopoeia will play an important role in improving the overall level of Chinese pharmacopoeia standards, strengthening drug quality control and improving drug quality.

Establishment of Determination of Fractal Dimension of Ethanol-precipitated Flocs of Two Root Medicinal Herbs / 中国实验方剂学杂志

Objective: To establish a method for the determination of fractal dimension of ethanol precipitation flocs in two kinds of root medicinal herbs (Astragali Radix and Isatidis Radix). Method: The ethanol-precipitated flocs of Astragali Radix and Isatidis Radix were taken as the research objects. Firstly, the original microscopic images of the ethanol precipitation flocs were binarized by Ostu algorithm. Secondly, the influence of sampling volume, dilution multiple, image magnification ratio and number of image acquisition sites on fractal dimension was investigated using perimeter-area method. Result: The ethanol precipitation flocs of Astragali Radix and Isatidis Radix had fractal characteristics. At the same time, the stable and reliable fractal dimension of the flocs could be obtained when the sampling volume was 600-800 μL, the sample was diluted to 5-20 times, the microscopic image was enlarged to 200 times or 400 times, and four different image acquisition sites were selected. Conclusion: The established method is stable and feasible, which can provide reference for the fractal theory of ethanol precipitation flocs of root medicinal herbs.

New phenotype caused by a NR5A1 heterozygous mutation—— 46, XX disorder of sex development / 中华内分泌代谢杂志

Objective To summarize the clinical manifestations of 46, XX ovotesticular disorder of sex development (DSD) caused by a NR5A1 heterozygous mutation. Methods The first case of 46,XX ovotesticular DSD was caused by a NR5A1 heterozygous mutation in China and was reported with a review of 11 similar cases in the literatures since July 2016. Results A 5. 6-year-old child raised as female was born with ambiguous genitalia. The left gonad was palpable in the inguinal region while the right one was located in abdomen. Gonadal histology showed both ovotestis. Vaginoscopy revealed a short, blind-ending vagina. No uterine was detected by laparoscopy. Repeated karyotype results were 46, XX with SRY gene negative. A heterozygous de novo mutation ( p. Arg92Trp) in the accessory DNA-binding region of NR5A1 gene was found in that child. Conclusions We reported for the first time in China a new phenotype caused by a NR5A1 heterozygous mutation-46,XX ovotesticular DSD. According to the review of literatures, such mutation seemed with incomplete penetrance. It could cause both 46, XX DSD and 46, XY DSD with varied manifestations. The possible underlying mechanism might relate to the impairment of the binding between the mutant protein and target DNA which might lead to a decreased inhibition of the male developmental pathway through downregulation of female antitestis genes.

Application of Microwave Drying and Sterilization Technology in TCM Field / 中国中医药信息杂志

Compared with traditional drying methods for Chinese materia medica, microwave drying technology is not only with the features of easy and convenient to operate, rapidity, good effects, well remained appearance of medicine and low energy consumption, but also with the feature of extraordinary sterilization effects at the same time with drying. This article introduced the features and effects of microwave drying and sterilization technology, reviewed its application in the TCM field, and proposed existing problems and prospects in the recent research by targeting security problems (microwave radiation and microwave residue).

New phenotype caused by a NR5A1 heterozygous mutation—— 46, XX disorder of sex development / 中华内分泌代谢杂志

Objective To summarize the clinical manifestations of 46, XX ovotesticular disorder of sex development (DSD) caused by a NR5A1 heterozygous mutation. Methods The first case of 46,XX ovotesticular DSD was caused by a NR5A1 heterozygous mutation in China and was reported with a review of 11 similar cases in the literatures since July 2016. Results A 5. 6-year-old child raised as female was born with ambiguous genitalia. The left gonad was palpable in the inguinal region while the right one was located in abdomen. Gonadal histology showed both ovotestis. Vaginoscopy revealed a short, blind-ending vagina. No uterine was detected by laparoscopy. Repeated karyotype results were 46, XX with SRY gene negative. A heterozygous de novo mutation ( p. Arg92Trp) in the accessory DNA-binding region of NR5A1 gene was found in that child. Conclusions We reported for the first time in China a new phenotype caused by a NR5A1 heterozygous mutation-46,XX ovotesticular DSD. According to the review of literatures, such mutation seemed with incomplete penetrance. It could cause both 46, XX DSD and 46, XY DSD with varied manifestations. The possible underlying mechanism might relate to the impairment of the binding between the mutant protein and target DNA which might lead to a decreased inhibition of the male developmental pathway through downregulation of female antitestis genes.

Application of Microwave Drying and Sterilization Technology in TCM Field / 中国中医药信息杂志

Compared with traditional drying methods for Chinese materia medica, microwave drying technology is not only with the features of easy and convenient to operate, rapidity, good effects, well remained appearance of medicine and low energy consumption, but also with the feature of extraordinary sterilization effects at the same time with drying. This article introduced the features and effects of microwave drying and sterilization technology, reviewed its application in the TCM field, and proposed existing problems and prospects in the recent research by targeting security problems (microwave radiation and microwave residue).

Status and suggestions for adjuvant standard for Chinese materia medica processing in China / 中国中药杂志

In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing.

Acupuncture combined with western medication for mild cognitive disorder after stroke: a rando- mized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To verify the clinical effect of the penetration acupuncture at the acupoints of governor vessel(GV) and bladder meridian on head for mild cognitive disorder after stroke.</p><p><b>METHODS</b>One hundred and ten patients were randomly divided into an observation group and a control group, 55 cases in each one. Penetration acupuncture was used at the acupoints of GV and bladder meridian on head in the observation group,namely Wuchu (BL 5) to Chengguang (BL 6) and Tongtian (BL 7) to Luoque (BL 8) bilaterally, and Shenting (GV 24) to Xinhui (GV 22), Qianding (GV 21) to Baihui (GV 20), Houding (GV 19) to Qiangjian (GV 18). Body acupuncture and conventional western medication were applied in the both two groups. Acupuncture was adopted once a day, five times a week and eight weeks totally. The changes of Montreal Cognitive Assessment (MoCA), Mini mental state examination scale(MMSE), self-rating depressive scale (SDS) and activities of daily living scale (Barthel index) were compared between the two groups before treatment, in the middle of treatment(at the forth week) after treatment(at the eighth week) and in three weeks after treatment(follow-up).</p><p><b>RESULTS</b>After treatment of four and eight weeks and at the time of follow-up, the results of MoCA, MMSE, SDS and Barthel index were apparently im proved compared with those before treatment in the two groups (all P < 0.01). After treatment of eight weeks and at the time of follow-up, the scores of MoCA and SDS were obviously improved in the observation group compared with those in the control group (P < 0.01, P < 0.05). The improvements of MMSE in the observation group were more marked than those in the control group at all times (P < 0.01, P < 0.05). But there was no statistical significance about the change of Barthel index between the two groups (all P > 0.05).</p><p><b>CONCLUSION</b>Penetration acupuncture at the acupoints of GV and bladder meridian on head can remarkablely improve the cognitive function of the patients with mild cognitive disorder after stroke,and have some efficacy of relieving the bad mood such as depression.</p>

Analysis of PCCA and PCCB gene mutations in patients with propionic acidemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze PCCA and PCCB gene mutations in 10 Chinese patients with propionic acidemia(PA).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. The 39 exons and flanking sequences of the PCCA and PCCB genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>DNA sequencing has revealed that 7 patients have carried a PCCA gene mutation, 2 patients carried PCCB gene mutation and 1 patient carried mutations in both PCCA and PCCB genes. Ten PA mutations were confirmed, including 8 affecting the PCCA gene and 2 affecting the PCCB gene. Three PCCA mutations c.245G>A, IVS15+5del5, c.1288C>T and 2 PCCB mutations c.838insC, c.1087T>C were found for the first time.</p><p><b>CONCLUSION</b>Among Chinese patients with propionic acidemia patients, their genetic mutations are mainly found on the PCCA gene.</p>

Analysis of ornithine transcarbamylase gene mutations in three boys affected with late-onset ornithine transcarbamylase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the types of OTC gene mutations in three male patients with late onset ornithine transcarbamylase deficiency (OTCD, MIM #311250).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. The 10 exons and their flanking sequences of the OTC gene were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Based on DNA sequence analysis, all of the three patients have carried OTC gene mutations. Patients 1 and 2 were both hemizygous for mutation c.586G> A(p.D196N). A novel mutation c.800G> C(p.S267T) were confirmed in patient 3.</p><p><b>CONCLUSION</b>p.S267T mutation has affected the conserved amino acid motif of the OTC protein, and is therefore a pathogenic mutation.</p>

Genetic analysis of ASS1, ASL and SLC25A13 in citrullinemia patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of Y9ASS1, ASL and SLC25A13 genes in four patients manifesting citrullinemia.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. Exons and their flanking sequences of the three genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Based on DNA sequence analysis, one case was diagnosed with argininosuccinate synthetase deficiency, and the mutation type (ASS1 gene) was c.236C>T (p.S79F) + c.431C>G (p.P144R). Two cases were diagnosed with argininosuccinic aciduria (ASL gene), and their gene mutations were c.434A>G (p.D145G) + c.1366C>T (p.R456W) and c.331C>T (p.R111W) + IVS8+2insT, respectively. A thirteen months boy who carried a heterozygous 851del4 mutation (SLC25A13 gene) was diagnosed with citrullinemia adult-onset type II.</p><p><b>CONCLUSION</b>Through analysis of relevant pathogenic genes, four patients have been diagnosed.</p>

Clinical investigation and mutation analysis of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and SLC25A13 gene mutations of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia.</p><p><b>METHODS</b>The patient was subjected to physical examination and routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic acids and galactose were analyzed respectively with tandem mass spectrometry and gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was conducted by high resolution melt (HRM) analysis.</p><p><b>RESULTS</b>The petechiae on the patient's face and platelet count (27×10(9)/L, reference range 100×10(9)/L-300×10(9)/L) supported the diagnosis of immunologic thrombocytopenic purpura (ITP). Laboratory tests found that the patient have abnormal coagulation, cardiac enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry also found methionine to be increased (286 μmol/L, reference ranges 8-35 μmol/L). The patient did not manifest any galactosemia, citrullinemia and tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct sequencing of exon 6 revealed a novel mutation c.495delA. The same mutation was not detected in 100 unrelated healthy controls. Further analysis of her family has confirmed that the c.495delA mutation has derived from her farther, and that the IVS16ins3kb was derived from her mother.</p><p><b>CONCLUSION</b>The clinical features and metabolic spectrum of citrin deficiency can be variable. The poor prognosis and severity of clinical symptoms of the patient may be attributed to the novel c.495delA mutation.</p>

Analysis of clinical features and GCDH gene mutations in four patients with glutaric academia type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations.</p><p><b>METHODS</b>The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered.</p><p><b>CONCLUSION</b>Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.</p>

Lidamycin inhibits the proliferation of HERG K+ channel highly expressing cancer cells and shows synergy with anticancer drugs / 药学学报

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.