OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

Objectives:To investigate the risk factors of sarcopenia in patients receiving maintenance peritoneal dialysis (MPD).Methods:One hundred and thirteen patients receiving maintenance MPD for ≥3 months during January and December 2017 were enrolled in this study. According to the Asian Working Group for Sarcopenia(AWGS)algorithm, there were 26 patients with sarcopenia accounting for 23.0% of all MPD patients. Demographic and anthropometric data were collected; laboratory tests were conducted, Kt/V urea and normalized protein equivalent of total nitrogen appearance were calculated; the bioelectrical impedance analysis (BIA) was performed and grip strength was tested. The nutritional status was evaluated with Subjective Global Assessment (SGA). Logistic regression was used to analyze the risk factors of sarcopenia in MPD patients. Results:BMI and dialysis dose of patients with sarcopenia were significantly lower than those without sarcopenia [(20.35±2.35) kg/m 2vs. (23.81±3.14) kg/m 2, t=-5.181, P<0.01; (5.57±1.83) L/d vs. (6.66±1.71) L/d, t=-2.795, P<0.01]. The bioelectrical impedance analysis showed that the total water content of patients with sarcopenia was higher than that of patients without sarcopenia [(35.44±6.40) kg vs. (28.52±4.89) kg, t=5.077, P<0.01]; while the protein content[(7.46±1.31) kg vs. (9.24±1.63) kg, t=-5.080, P<0.01] and skeletal muscle content [(20.54±4.18) kg vs. (25.88±4.95) kg, t=-4.980, P<0.01] of patients with sarcopenia were lower than those without sarcopenia. Multivariate analysis showed that decreased BMI( OR=0.934, 95 %CI: 0.723-0.998, P<0.01) and body protein ( OR=0.927, 95 %CI: 0.698-0.996, P<0.01), increased total body water( OR=1.382, 95 %CI: 1.053-1.813, P=0.02) were independent risk factors for sarcopenia in MPD patients. Conclusion:The incidence of sarcopenia in MPD patients is high, which is associated with the excessive volume load and malnutrition of patients.

Objective:To investigate the characteristics of macular perfusion and structures in patients with early stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).Methods:A cross-sectional study was performed.Forty eyes of 27 diabetic patients without diabetic retinopathy (NDR), forty eyes of 24 patients with mild non-proliferative diabetic retinopathy (NPDR) and forty eyes of 28 patients with moderate NPDR were recruited in Guangdong Provincial People's Hospital from June 2017 to August 2018.RTVue-XR OCTA was used to scan a 6 mm×6 mm area centered in the fovea and the superficial vascular complex (SVC) and deep vascular complex (DVC) vessel density, fovea avascular zone (FAZ) area, FAZ perimeter, acircularity index (AI), and vessel density of a 300 μm wide ring area around FAZ (FD300) were quantified.The associations among stages of DR and macular vessel density, structures were analyzed.This study was approved by the Ethics Committee of the Guangdong Provincial People's Hospital (No.2016232A).Results:The vessel density of SVC and DVC tended to decrease as the progression of DR.The vessel density of SVC was (51.25±3.27)%, (48.81±3.99)%, (47.00±3.49)%, (45.73±3.35)%, and the vessel density of DVC was (53.89±6.30)%, (49.94±6.05)%, (46.69±4.87)% and (44.78±4.30)% in the control group, NDR group, mild NPDR group, and moderate NPDR group, respectively.The vessel densities of SVC and DVC were statistically different among the four groups ( F=18.33, 21.53; both at P<0.01). The vessel density of SVC and DVC in the NDR group, mild NPDR group, moderate NPDR group was significantly lower than that in the control group (all at P<0.01). The vessel densities of FD300 in the mild NPDR group and moderate NPDR group were significantly lower than that in the control group (all at P<0.01). The FAZ area of the control group, NDR group, mild NPDR group, and moderate NPDR group was (0.31±0.11), (0.32±0.09), (0.34±0.13), and (0.37±0.10)mm 2, respectively.There was no significant difference in the FAZ area among the four groups ( F=2.18, P=0.09). The FAZ perimeter and AI were significantly higher in the moderate NPDR group than those in the control group (both at P<0.05). Conclusions:OCTA is able to detect the decrease of vessel density in diabetic patients before the occurrence of visible fundus lesions.The vessel density of SVC and DVC in patients with early stages of DR is decreased.DVC vessel density may be a sensitive marker to indicate DR.FD300 is not significantly decreased until mild NPDR, FAZ area and perimeter are significantly increased in moderate NPDR, indicating a more irregular FAZ.

Objective To analyze the research status of infants' complementary feeding and to summarize the research hotspots in this field.Methods Literature related to infants' complementary feeding was retrieved published in CNKI and WanFang date knowledge service platform from database created to May 2017. The method of bibliometrics and social network analysis were used to analyze these articles retrieved in publishing year, agencies, journals.Results A total of 1595 articles were searched publishing in 477 periodicals. The quantity of literature showed an increasing trend. There were 30 high-frequency keywords such as complementary feeding, breast feeding, growth and development as well as iron-deficiency anemia. A total of 10 major research institutions were included, for example, the Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine and Sichuan University.Conclusions The current research hotspots focus on the effects of complementary feeding on infants' growth and development as well as nutrition, investigation analysis on infants' complementary feeding in the countryside, correlation analysis between complementary feeding and iron-deficiency anemia. Various research methods should be taken to carry studies related to knowledge on complementary feeding for infants' parents and behavior on complementary feeding.

Objective To investigate the relationship between BRCA1 protein expression in lung cancer tissues and the effect of gemcitabine and Cisplatin based chemotherapy.Methods 80 cases of squamous cell carcinoma confirmed by pathology from May 2013 to May 2015 were selected, and treated with gemcitabine plus cisplatin chemotherapy and Ginseng and Astragalus assisted theropy.BRCA1 protein expression of all patients were detected, and relationship between the effect of chemotherapy and prognosis of patients with BRCA1 protein expression in lung cancer tissues were studied.Results In 80 cases, BRCA1 protein was positive in 40 cases, 40 cases were negative, CR 5 patients, PR 6 patients with BRCA1 positive expression, the remission rate was lower than the BRCA1 negative patients ( P <0.05 ) .80 cases of adverse reactions were seen as leukopenia, gastrointestinal symptoms (nausea and vomiting), abnormal liver function, BRCA1 expression of peripheral neurotoxicity, the incidence of complications in patients with positive expression were significantly higher than BRCA1 negative patients(P<0.05).N stage (P=0.03), BRCA1 gene (P=0.02) were independent risk factors of the prognosis of patients.Conclusion BRCA1 protein positive patients in lung cancer tissue had poor chemotherapy effect, more adverse reactions, and poor prognosis.

Objective To study the effects and mechanism of calycosin on oxidative stress andβ-cell apoptosis induced by streptozotocin (STZ). Methods RIN-m5F cells were divided into 5 groups:control group, STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. The control group did not receive any treatment, while streptozotocin was added to the final concentration of 10 mmol/L in STZ group, STZⅠgroup, STZⅡgroup and STZⅢgroup. After the incubation with STZ for 6 h, calycosin was added to a final concentration of 10, 50 and 100 μmol/L in STZⅠgroup, STZⅡgroup and STZⅢgroup respectively. The cell viability and apoptosis was detected by CCK-8, LDH, caspase 3 and Tunel assay. The intracellular oxidative stress was measured using mitochondrial membrane potential, DCFH-DA, SOD activity and malondialdehyde levels assay. RIN-m5F cells were divided into control group, calycosinⅠgroup, calycosinⅡgroup and calycosinⅢgroup, which were treated with different concentrations (0,10, 50 and 100 μmol/L, respectively) of calycosin. The expression of NF-E2-related factor 2(Nrf2) in RIN- m5F cells was detected by Western blot. The translocation of Nrf2 was detected by immunofluorescence. In RIN-m5F cells were divided intoⅢgroup andⅣgroup,Ⅳgroup was pre-treated with protein kinase C(PKC) inhibitor. The effects of calycosin on Nrf2 translocation, oxidative stress and apoptosis were also observed. Results STZ could induce the accumulation of reactive oxygen species and apoptosis in RIN-m5F cells. Calycosin did not affect normal RIN-m5F cells, whereas it reduced the oxidative stress and apoptosis induced by STZ in a dose-dependent manner. The expression of Nrf2 in RIN-m5F cells was not affected by calycosin, whereas it promoted the translocation of Nrf2 into nucleus. The ability of calycosin promoting Nrf2 translocation was decreased after PKC inhibitor treatment, and PKC inhibitor could also significantly attenuate the anti-oxidant and anti-apoptotic ability of calycosin. Conclusions This study shows that calycosin may play an anti-oxidative and anti-apoptotic role by activating PKC to promote Nrf2 translocation, which is expected to be used as a new clinical drug for the prevention and treatment of diabetes mellitus.

Objective To investigate the characteristics of auditory nerves and brainstem pathways,patho-physiological and nerve damages and the correlation between oxygen indexes,and the values of high stimulation ABR in patients with OSAHS.Methods Auditory brain stem responses (ABR)at rates of 11.1 times/s,31.1 times/s,51.1 times/s were performed in both the moderate-to-severe OSAHS group(5 cases of moderate and 34 cases of severe,in total of 39 cases ,78 ears)and the control group (34 cases,68 ears).According to the character-istics of ABR,the correlation with parameters of blood oxygen was studied.Results At the rate of 11.1 times/s, wave V latencies (5.79±0.22 ms)in OSAHS patients were longer than that in the control group.At the rate of 31.1 times/s,wave V latencies (5.98±0.19 ms)and waveⅠ(1.85±0.18 ms)in OSAHS patients were prolonged more than those in the control group.At the rate of 51.1 times/s,wave V latencies (6.09±0.25 ms)and waveⅠ(1.94±0.26 ms)in OSAHS patients were longer than those in the control group.Increasing stimulation rates from 11.1 times/s to 31.1 times/s showedΔⅠwas longer in OSAHS group(0.12±0.17 ms)than in the control group (0.07±0.11 ms).Increasing stimulation rates from 11.1 times/s to 51.1 times/s showedΔⅠwas longer in OS-AHS group(0.21±0.25 ms)than in the control group(0.15±0.10 ms).All above had correlations with hypoxia. Conclusion High stimulation rates in ABR by amplifying the waveⅠ latency confirm cochlear and auditory nerve damages near the cochlear segment in patients with moderate to severe OSAHS.Therefore the study of nerve injury in OSAHS patients should take blood oxygen saturation and hypoxia percentage rather than AHI.

Objective To evaluate the diagnostic accuracy of CMS50F for screening in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods Sixty-four volunteers with suspected OSAHS underwent simultaneous noc?turnal polysomnography (PSG), micromovement sensitive mattress sleep monitoring system(MSMSMS)and CMS50F. The ap?nea-hypopnea index (AHI) detected by PSG and MSMSMS was used as the diagnostic standard for OSAHS. The reliability of CMS50F for monitoring sleep was assessed. Results There was no statistic difference in CMS50F-ODI3 and PSG-AHI be?tween normal, mild and moderate OSAHS groups(P>0.05). The CMS50F-ODI3 was smaller than the PSG-AHI in severe OSAHS patients(P < 0.05). There was a positive correlation between CMS50F-ODI3 and PSG-AHI(r=0.855, P < 0.05). PSG-AHI≥5 events per hour was used as the threshold value to diagnose OSAHS, the sensitivity and specificity of CMS50F were 94.5%and 88.9%. There were no significant differences in CMS50F-ODI3 and MSMSMS-AHI between normal, mild and moderate OSAHS patients(P>0.05). The value of CMS50F-ODI3 was smaller than MSMSMS-AHI in severe OSAHS patients (P < 0.05). There was also a significant correlation between CMS50F- ODI3 and MSMSMS-AHI (r=0.867,P <0.05). MSMSMS-AHI≥5 events per hour was used as the threshold value to diagnose OSAHS, the sensitivity and specificity of CMS50F were 94.5%and 88.9%. Conclusion CMS50F can be used as a portable and reliable device for screening of pa?tients suspected OSAHS.

Objective To explore the roles of spinal microglial Src-family kinases (SFKs) in diabetic neuropathic pain. Methods Male Sprague-Dawley rats, weighing 200 ~ 220 g, were used in the experiments. The level of p-SFKs in spinal dorsal horn was detected by single immunofluorescence staining on day 7th , 14th and 28th after intraperitoneally injection of Streptozotocin (STZ) and its location was detected by double immunofluorescence staining. The changes of 50% paw-withdrawal thresholds of rat were detected by behavioral tests when PP2 , a specific inhibitor of SFKs , was intrathecally administered before intraperitoneally injection of STZ. Results Compared with vehicle group, the blood glucose level increased on day 1 (P < 0.001) and the hyperglycemia persisted at least for 28 days (P < 0.001) after intraperitoneally administered of STZ (50 mg/kg). Paw-withdrawal threshold (PWT) decreased gradually from day 1 (P < 0.05) and reached the minimum on day 28 (P < 0.001) after STZ administration. Meanwhile, the expression of p-SFKs in spinal dorsal horn markedly increased on day 7 (P < 0.01), day 14 (P < 0.01) and day 28 (P < 0.01). The p-SFKs was mainly co-localized only with microglia , but not with neurons or with astrocytes. Intrathecally administered of PP2 before STZ reversed STZ-induced mechanical hyperalgesia. Conclusion Microglial SFKs in spinal dorsal horn maybe play a pivotal role in diabetic neuropathic pain.