A novel compound heterozygous mutation in G6PC gene causes type Ⅰa glycogen storage disease with secondary gout / 中华内分泌代谢杂志

Objective:To investigate the clinical characteristics and genetic mechanism of a patient with gout and hyperlipidemia.Methods:Clinical data of patient and his parents were collected in details, including their medical histories, physical examination results, and laboratory tests. DNA was extracted from the peripheral blood of the patient and their parents for whole exome sequencing. Protein function was predicted for new mutations.Results:The patient was a 22-year-old male with typical clinical manifestations of hypoglycemia, hyperuricemia, gout, and hyperlipidemia. c. 260delG(p.V88Ffs*13)frameshift mutation was detected in the second exon of the patient′s glucose-6-phosphatase(G6PC) gene, and c. 532C>G(p.P178A)missense mutation was detected in the fourth exon. The father and mother of the patient were heterozygotes carrying c. 260delG(p.V88Ffs*13)and c. 532C>G(p.P178A)mutations, respectively. Protein structure prediction showed that mutations were able to cause protein structure changes. The patient was diagnosed as glycogen storage disease type Ⅰa(GSD-Ⅰa)with secondary gout.Conclusions:The compound heterozygous mutation of G6PC gene is the pathogenic basis of this gout patient. The discovery of the new pathogenic mutation c. 260delG(p.V88Ffs*13)of the G6PC gene broadened the spectrum of pathogenic genes of GSD-Ⅰa and gout in Chinese patients.

Annexin A2 gene interacting with viral matrix protein to promote bovine ephemeral fever virus release

Bovine ephemeral fever virus (BEFV) causes bovine ephemeral fever, which can produce considerable economic damage to the cattle industry. However, there is limited experimental evidence regarding the underlying mechanisms of BEFV. Annexin A2 (AnxA2) is a calcium and lipid-conjugated protein that binds phospholipids and the cytoskeleton in a Ca 2+ -dependent manner, and it participates in various cellular functions, including vesicular trafficking, organization of membrane domains, and virus proliferation. The role of the AnxA2 gene during virus infection has not yet been reported. In this study, we observed that AnxA2 gene expression was up-regulated in BHK-21 cells infected with the virus.Additionally, overexpression of the AnxA2 gene promoted the release of mature virus particles, whereas BEFV replication was remarkably inhibited after reducing AnxA2 gene expression by using the small interfering RNA (siRNA). For viral proteins, overexpression of the Matrix (M) gene promotes the release of mature virus particles. Moreover, the AnxA2 protein interaction with the M protein of BEFV was confirmed by GST pull-down and coimmunoprecipitation assays. Experimental results indicate that the C-terminal domain (268– 334 aa) of AxnA2 contributes to this interaction. An additional mechanistic study showed that AnxA2 protein interacts with M protein and mediates the localization of the M protein at the plasma membrane. Furthermore, the absence of the AnxA2-V domain could attenuate the effect of AnxA2 on BEFV replication. These findings can contribute to elucidating the regulation of BEFV replication and may have implications for antiviral strategy development.

Analysis of clinical characteristics and related influencing factors of patients with early-onset gout / 中华内分泌代谢杂志

Objective:To investigate the clinical features and influencing factors of early-onset gout.Methods:Male patients with gout admitted to Department of Endocrinology and Metabolism were recruited from 2015 to 2018. Patients with gout onset before age 30 were defined as the " early-onset" group, and those with onset at 30~60 years were defined as the "late-onset" group. Clinical characteristics were compared between two groups. Factors associated with early-onset gout were analyzed.Results:A total of 1 243 male patients were enrolled in this study; 480 individuals were in the early-onset, and 763 in the late-onset groups. Compared with the late-onset group, patients with early-onset gout had higher consumption rates of sugar-sweetened beverage(28.0% vs 15.0%, P=0.001), a higher homeostasis model assessment for insulin resistance level(3.78±2.93 vs 3.10±2.39, P<0.01), and larger proportions of family histories of diabetes(30.8% vs 20.4%, P<0.01)and hypertension(51.2% vs 42.6%, P=0.003). Logistic regression analysis showed that factors associated with early-onset gout were drinking sugar-sweetened beverage( P=0.012), family history of diabetes( P=0.037). Conclusion:Early-onset gout was associated with a family history of diabetes. Patients with family histories of diabetes are more likely to have early-onset gout, which may be associated with a common genetic basis.

Clinical research on application of carbon nanoparticle for tracing sentinel node in early gastric cancer / 重庆医学

Objective To explore the application of carbon nanoparticles for tracing sentinel node(SN) in early gastric cancer (EGC).Methods Forty-six patients with EGC conducted subserous injection of carbon nanoparticle solution 1.0 mL at 4-6 points around tumor during operation.SN was examined by adopting 3 different methods.The first stained lymph node was defined as the first SN(FSN),and the whole group lymph nodes were identified as the group SN(GSN) and all lymph nodes colored within 5 min were labeled as the all SN(ASN).The affirmative SN and other resected lymph nodes were performed the histopathological examination and comparison.Resnlts In all 46 cases,SN was successfully detected out with the detection rate of 100％;the number of SN,GSN and ASN were 1.04 ± 0.21,3.93-±-1.90 and 13.61 ± 4.36 respectively,the difference in SN number among 3 different methods had statistical significance(P＜0.05).The accuracy rates of FSN,GSN and ASN for judging perigastric lymph node metastasis status were 95.65％,100％ and 100％,respectively.Conclusion The carbon nanoparticles tracing SN in EGC has higher staining rate and higher accuracy for predicting lymph node metastasis;GSN has high accuracy,moreover has less trauma and is most suitable method for detecting SN.

Observation of Fluorouracil Implants on the Intraperitoneal Chemotherapy Safety of Advanced Gastric Cancer Patients / 中国药房

OBJECTIVE:To investigate the effects of Fluorouracil implants on intraperitoneal chemotherapy safety of advanced gastric cancer patients. METHODS:The information of 264 patients with advanced gastric cancer were analyzed retrospectively. All patients were given Fluorouracil implants 800 mg,scattered into the mesenteric and surgical area,dose of each implantation site less than 200 mg,the distance of implantation range from incision and anastomosis more than 3 cm. All patients were given second generation cephalosporin 30 min before operation,at 3rd h during operation,1-3 d after operation. The occurrence of complications and ADR during hospitalization were observed after operation. RESULTS:After operation,6 patients suffered from complications, with incidence of 2.28%,including 3 cases of gastrointestinal reaction,2 cases of anastomotic bleeding and 1 case of anastomotic leakage. Routine blood test and liver and kidney function were rechecked 3 d after operation,mainly thrombocytopenia and liver function injury,with the incidence of 2.65%. CONCLUSIONS:Fluorouracil implants can be used for intraperitoneal chemotherapy of advanced gastric cancer patients. However,attention should be paid to thrombocytopenia and liver function injury.

The expression of X-linked inhibitor of apoptosis protein and cell apoptosis in caerulein-stimulated rat pancreatic acinus AR42J cell lines / 生物医学工程学杂志

To study the expression of X-linked inhibitor of apoptosis protein (XIAP) and cell apoptosis in vitro model of acute pancreatitis (AP), we carried out experiments to stimulate AR42J cell line with caerulein (10(-8) mol/L) for 12 hours, then collected cells at various time points (0 h, 4 h, 8 h, 12 h, and 24 h, respectively). We then observed the morphologic changes of AR42J cells with the stimulation of caerulein with electronic microscope. The gene expression of XIAP, caspase-3 and caspase-9 was detected using real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), and the protein expression of XIAP was assessed by western blot. The activation of nuclear factor-kappa B (NF-kappaB) was measured by flow cytometry (FCM). With the stimulation of caerulein, the expression of XIAP and the NF-kappaB activation could first decrease and then increase, but the change of caspase-3 and caspase-9 expressions were opposite. XIAP may inhibit the cell apoptosis in rat pancreatic acinus AR42J cell lines at first with the stimulation of caerulein, then NF-kappaB can upgrade the expression of XIAP and increase the cell apoptosis.