Professor Takeyori Saheki's team at Kagoshima University, Japan, published a paper in Nature Genetics in June 1999, pinpointing the pathogenic gene for adult-onset type Ⅱ citrullinemia as SLC25A13 and naming the protein product encoded by this gene as citrin. Over the past 25 years, the researches have made positive progress on the pathophysiological mechanism, clinical phenotype, molecular diagnosis, treatment, and prognosis of citrin deficiency (CD) as an autosomal recessive genetic disease. Currently, three age-dependent clinical phenotypes of CD have been found, namely neonatal intrahepatic cholestasis caused by citrin deficiency, failure to thrive and dyslipidemia caused by citrin deficiency, and adult-onset type Ⅱ citrullinemia. Although relevant internal medicine drugs are being researched and developed while liver transplantation has been used for the treatment of CD patients, scientific dietary therapy remains the foundation, core, and key for the management of this disease. Furthermore, CD management involves the full life cycle of patients, requiring the joint efforts of basic and clinical medicine as well as systematic articulation at multi-levels, such as the parents, family, and society. By full-cycle, multidisciplinary, and systematic management, it is an achievable goal for CD patients to learn, work, and live in a healthy manner.

Objective:To explore the clinical utility of liquid chromatography tandem mass spectrometry forprimary aldosteronism screening.Methods:From January to October 2019, 413 inpatients diagnosed hypertension from Fuwai Hospital of Chinese Academy of Medical Sciences were enrolled, including 60 Primary aldosteronism(PA)patients and 353 primary hypertension patients. The plasma aldosterone concentration (PAC) and renin concentration (DRC) were measured after 2 h of standing. The 24 h urine samples were collected for measurement of aldosterone using LC-MS/MS. The performance of urine aldosterone and urine aldosterone/renin ratio (UADRR) in PA screening was evaluated by ROC, and compared with PAC/DRC ratio (ADRR). Meanwhile, the efficiency of urine aldosterone in elderly patients or patients with low blood potassium or 24 h urine sodium over 200 mmol was investigated.Results:Area under the curve (AUC)of urine aldosterone was 0.725 (95 %CI 0.679-0.767), and the best cut-off was 7.13 μg/24 h, which was lower than AUC of ADRR (0.958, 95 %CI 0.934-0.975). The AUC of UADRR was 0.947 (95 %CI 0.920-0.966), the best cut-off was 1.11 (μg/24 h)/(μIU/ml), the sensitivity and specificity were 91.7% and 89.0%, respectively. There is no significant differences found with ADRR. In patients with 24 h urine sodium over 200 mmol, AUC of aldosterone was 0.834 (95 %CI 0.730-0.910) and the best cut-off was 9.31 μg/24 h. The sensitivity and specificity were 90.9% and 68.7%, respectively. For the elderly patients over 60 years old, the AUC of urinary aldosterone was 0.860 (95 %CI 0.770-0.925), and the best cut-off was 6.91 μg/24 h. The sensitivity and specificity were 84.6% and 81.3%, respectively. When admission blood potassium was less than 3.50 mmol/L, AUC of urinary aldosterone was 0.822 (95 %CI 0.684-0.917), and the best cut-off was 10.63 μg/24 h. The sensitivity and specificity were 85.7% and 66.7%, respectively. Conclusion:The detection of aldosterone in urine by LC-MS/MS can provide clinical information for PA screening, and the screening performance is better in patients with 24-hour urine sodium over 200 mmol, elderly patients or patients with low blood potassium. If combined with renin, screening efficiency was the same as that in ADRR.

OBJECTIVETo detect potential mutation of the AGL gene in two siblings affected with glycogen storage disease type IIIa.

METHODSClinical data of the two siblings was collected and analyzed. Genomic DNA was extracted from peripheral venous blood samples from the patients and their parents. All exons and their flanking sequences of the AGL gene were subjected to PCR amplification and Sanger sequencing. Suspected mutation was verified in 75 healthy controls.

RESULTSThe main clinical features of the two siblings included hypoglycemia and hepatomegaly, along with markedly elevated liver and myocardial enzymes. Genetic analysis revealed that both siblings harbored compound heterozygous mutations c.1735+1G>T and c.959-1G>C of the AGL gene. Among these, the splicing mutation c.959-1G>C was a novel one with an allele frequency of <1%.

CONCLUSIONBased on their clinical features and genetic analysis, the siblings were diagnosed with glycogen storage disease type IIIa. The c.959-1G>C has enriched the spectrum of AGL gene mutations.

Adolescent ; Amino Acid Sequence ; Female ; Glycogen Debranching Enzyme System ; genetics ; Glycogen Storage Disease Type III ; genetics ; Humans ; Infant ; Male ; Mutation ; genetics ; Siblings

Objective: To prepare ibuprofen sustained-release dropping pills, to evaluate the accumulative release percentage in vitro and to study the drug state in the base.Methods: With the drug content, mass ratio of water-soluble base to insoluble base and mass ratio of stearic acid to glyceryl monostearate as the investigation factors, and the comprehensive score of 2-hour and 10-hour cumulative dissolution rate as the evaluation index, a Box-Behnken response-surface method was used to screen the optimal formula of ibuprofen sustained-release dropping pills.The drug state in the matrix was examined by differential scanning calorimetry (DSC).Results: The optimal formula of ibuprofen sustained-release dropping pills was as follows: the drug content of 10%, water-soluble and insoluble matrix ratio of 4∶1, and stearic acid and glyceryl monostearate ratio of 3∶1.The maximum cumulative dissolution rate of ibuprofen sustained-release dropping pills was 78.85%.The DSC analysis showed that the drug crystallization peak disappeared in the sustained-release dropping pills, and formed a solid dispersion.Conclusion: The preparation has good sustained-release effect, and the preparation process is simple.

OBJECTIVETo investigate the clinical features and AGL gene mutations in a family with glycogen storage disease type IIIa (GSD IIIa).

METHODSClinical data for diagnosis, treatment and follow-up of a sick child with GSD III was collected and analyzed. Genomic DNA was extracted from the peripheral blood samples from the patient and his parents. Polymerase chain reaction and direct DNA sequencing were utilized to analyze all of the exons of the AGL gene.

RESULTSThe genotype of the child was found to be c.3710_3711delTA/IVS14+1G>T. The former was a maternally-inherited mutation, which has not been reported previously. The latter was an abnormal splice-site mutation inherited from the father.

CONCLUSIONBased on its clinical and molecular evidences, the patient was diagnosed as GSD IIIa in conjunction with retrobular optic neuritis.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child, Preschool ; China ; Female ; Glycogen Debranching Enzyme System ; genetics ; metabolism ; Glycogen Storage Disease Type III ; enzymology ; genetics ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Point Mutation

Three new glucosylated caffeoylquinic acid isomers (1-3), along with six known compounds, have been isolated from an aqueous extract of the flower buds of Lonicera japonica. Structures of the new compounds were determined by spectroscopic and chemical methods as (-)-4-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (1), (-)-3-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (2), and (-)-5-O-(4-O-β-d-glucopyranosylcaffeoyl)quinic acid (3), respectively. In the preliminary in vitro assays, two known compounds methyl caffeate and 2'-O-methyladenosine showed inhibitory activity against Coxsackie virus B3 with IC50 values of 3.70 μmol/L and 6.41 μmol/L and SI values of 7.8 and 12.1, respectively.

Objective To detect the expression of SSX and to correlate it with clinical indicators of primary hepatocellular carcinoma (HCC).Methods The expression of SSX1-5 mRNA and SSX1 protein were respectively detected by RT-PCR and Western blot and immunohistochemistry staining.The relation between the expression of SSX mRNA and SSX1 protein with clinical indicators were analysed.Results SSX1,SSX2,and SSX3 mRNA were expressed in hepatocellular carcinoma cell lines BEL-7404,Hep G2,and SMMC-7721.In 26 HCC samples,SSX1-SSX5 mRNA was detectable in 53.8％,42.3％,50.0％,46.2％ and 26.9％.The expression of SSX1 mRNA was not related to serum AFP levels (P ＞0.05).Specific expression was both found in the normal group and the high value group.The expression rate of SSX1 mRNA was 85.7％ in the older group,which was higher than in the younger group (16.7％,P ＜ 0.05).The expression rate of SSX1 protein was 50％ in HCC tissues,which was not seen in the caner-adjacent or cirrhosis tissues.In 49 HCC paraffin tissue section samples,the expression rate of SSX1 protein was higher than that in caner-adjacent tissues (46.9％ vs 18.4％,P ＜ 0.05).The expression rate of SSX1 protein was 68.3％ in the large hepatocellular carcinoma group,which was higher than in the small hepatocellular carcinoma group (29.6％),(P ＜ 0.05).Conclusions SSX1 mRNA is expressed with a high percentage and specificity in HCC and their products are new potential promising targets for antigen-specific immunotherapy of HCC.The detection of SSX1 expression has the potential value for auxiliary diagnosis of HCC.

OBJECTIVETo study the chemical constituents of Iodes cirrhosa and evaluate their bioactivity.

METHODThe compounds were isolated and purified by various kinds of column chromatography methods and their structures were determined by spectroscopic data analysis. Neuroprotective assay against serum deprivation induced SH-SYSY-JNK3 cell apoptosis was evaluated by MTr method while potassium channel-blocking activity was assayed in both non-specific and specific K+ channel-regulator screening models.

RESULTTwenty-one compounds were obtained from an EtOAc portion of an ethanolic extract of the root of I. cirrhosa. Their structures were elucidated as 1beta, 3beta-dihydroxyurs-9(11),12-diene(1), bauerenyl acetate(2),3beta-hydroxy-11-oxo-olean-12-enyl palmitate(3), 3beta-acetoxy-urs-12-ene-11-one(4), betulinic acid(5), stigmasta-5, 22-diene-3beta-ol(6), 7beta-hydroxystigmasterol(7), stigmasta-5, 22diene-3beta-ol3-O-beta-D-glucopyranoside(8),scopoletin(9),scopolin(10),clovamide(11),methyl 3,5-di-O-caffeoylquinate(12),3,5-dicaffeoylquinic acid(13),2,6-dimethoxy-1,4-benzoquinone(14), protocatechualdehyde(15), vanillin(16), protocatechuic acid(17), vanillic acid(18),caffeic acid(19),azelaic acid(20),and succinic acid(21). Compound 3,4,6,9,10,14,15,18 and 20 showed neuroprotective activities against serum deprivation induced SH-SYSY-JNK3 cell apoptosis at a concentration of 1.0 x 10(6) mol x L(1) with relative protection rates of 177%, 144%, 137%, 137%, 143%, 145%, 137%, 189%, 130%, respectivley. Compound 16 could increase DiBAC4(3) fluorescence response in both non-specific and specific K+ channel-regulator screening models at the concentration of 1.0 x 10(-5) mol x L(-1).

CONCLUSIONCompound 1 was a new compound and all compounds were isolated from this genus for the first time. Compounds 3,4,6,9,10,14,15,18 and 20 showed neuroprotective activities while 16 exhibited K+ channel-blocking activity.

Apoptosis ; drug effects ; Cell Line, Tumor ; Humans ; Magnoliopsida ; chemistry ; Neuroprotective Agents ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology ; Potassium Channels ; drug effects

OBJECTIVETo investigate chemical constituents of Iodes cirrhosa.

METHODConstituents were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic and chemical methods.

RESULTTwenty-four compounds were obtained from a H2O-soluble portion of an ethanolic extract of the root of lodes cirrhosa Turcz. Structures of the isolates were identified as (-)-(7R,8S,7'E) -4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8,4'-oxyneolign-7'-ene-9'-O-beta-D-glucopyra-noside (1), (-)-(7S,8S,7'E)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8,4'-oxyneolign-7'-ene-9'-O-beta-D-glucopyranoside(2), (+)-(7S,8S)-syringylglycerol 8-O-beta-D-glucopyranoside (3), (+)-(7S, 8S)-guaiacylglycerol 8-O-P-D-glucopyranoside (4), (-)-(7S, 8S)-4,7,9, 9'-tetrahydroxy-3,3'-dimethoxy-8,4'-oxyneolignan-7-O-beta-D-glucopyranoside (5),(-)-alaschanisoside A (6), (-)-(2R)-1-O-beta-D-glucopyranosyl-2-(2-methoxy-4-[1-(E)-propen-3-ol] phenoxyl propane-3-ol(7), (-)-(2R)-1-O-beta-D-glucopyranosyl-2-{2,6-dimethoxy-4-[1-(E)-propen-3-ol] phenoxyl} propane-3-ol(8), (-)-liriodendrin(9), (-)-(7S, 8R)-guaiacylglycerol 9-O-beta-D-glucopyranoside(10), (-)-(7R, 8R)-guaiacylglycerol 9-O-beta-D-glucopyranoside(11),(-)-(7R,8R)-syringylglycerol 9-O-beta-D-glucopyranoside(12), (-)-(7R,8R)-guaiacylglycerol 7-O-beta-D-glucopyranoside(13), (-)-11,13-dihydrodeacylcynaropicrin 3-O-beta-D-glucopyranoside(14), (-)-sweroside (15), (-)-2-hydroxy-5-(2-hydroxyethyl) phenyl beta-D-glucopyranoside(16), (-)-(1'R)-1'-(3-hydroxy-4-methoxyphenyl) ethane-1',2'-diol-3-O-beta-D-glucopyranoside(17), (-)-tachioside(18), (-)-3,5-dimethoxy-4-hydroxyphenyl beta-D-glucopyranoside(19), (-)-3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone-3-O-beta-D-glucopy ranoside(20), (-)-2-methoxy4-(1-propionyl) phenyl beta-D-glucopyranoside(21), (-)-4-propionyl-3, 5-dimethoxyphenyl beta-D-glucopyranoside(22), erigeside C(23), and scopoletin beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside(24).

CONCLUSIONCompounds 1-24 were obtained from the genus for the first time.

Drugs, Chinese Herbal ; analysis ; Ethanol ; chemistry ; Glucosides ; analysis ; Isomerism ; Magnoliopsida ; chemistry ; Plant Roots ; chemistry ; Solubility ; Water ; chemistry

Objective To investigate the appropriate reconstruction techniques of multi-detector-row spiral CT angiography (MDCTA) to depict the collateral vessels in cavernous transformation of the portal vein (CTPV) caused by tumor thrombosis of hepatocellular carcinoma (HCC). Methods MDCTA scanning was performed during the portal venous phase after intravenous contrast materials in 18 HCC patients with CTPV induced by tumor thrombosis. Raw data were reconstructed with thin slice thickness followed by 2D and 3D angiographic reconstruction methods, including maximum intensity projection(MIP), shade surface display (SSD) and volume rendering technique(VRT). Results MDCTA with MIP reconstruction accurately depicted both the tumor thrombus within the portal vein and the collateral vessels of CTPV including the biliary (cystic vein and pericholedochal veinous plexus) and the gastric (left and right gastric veins) branches. However, VRT and SSD methods did poorly in showing the tumor thrombus and the collateral vessels. Conclusion MDCTA with MIP reconstruction is the method of choice to evaluate the collateral vessels of CTPV.