Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.

Objective: To investigate vitamin D levels among primary and middle school students in Xicheng District, Beijing Municipality, and to examine the association of vitamin D levels with hemoglobin (Hb) and serum ferritin (SF) levels, so as to provide insights into the prevention of anemia among primary and middle school students. Methods: The first, third and fifth grade primary school students and the first grade junior high school students were sampled from Xicheng District in 2019, using the multistage stratified cluster sampling method, and students' gender, age, height, weight and Hb levels were collected. The 25-hydroxyvitamin D [25-( OH )D] was measured using electrochemiluminescence assay, and SF was detected using immunoturbidimetry. The vitamin D deficiency was determined according to the American College of Endocrinology guidelines. The associations of 25-( OH) D levels with Hb and SF levels were examined using Pearson correlation analysis and Spearman rank correlation analysis. Results: Totally 403 primary and junior high school students were investigated, including 196 boys ( 48.64% ) and 207 girls ( 51.36% ). There were 179, 114 and 110 students at ages of 6 to 8 years ( 44.41% ), 9 to 11 years ( 28.29% ) and 12 to 13 years ( 27.30% ), respectively. The mean 25-( OH )D level was ( 14.80±5.96 ) ng/mL among the study students, and there were 90 students ( 22.33% ) with severe vitamin D deficiency, 243 students ( 60.30% ) with vitamin D deficiency, 63 students ( 15.63% ) with vitamin D inadequacy and 7 students ( 1.74% ) with vitamin D sufficiency. The mean Hb level was ( 136.28±8.33 ) g/L and the median SF level (interquartile range) was 56.80 (14.36) ng/mL among the study students, respectively. The 25-( OH )D level positively correlated with Hb ( r=0.364, P<0.001 ) and SF levels ( rs=0.374, P<0.001 ), and after adjustment for age and body mass index, the 25-( OH )D still correlated positively with Hb ( r=0.157, P=0.048 ) and SF levels ( rs=0.174, P=0.022 ) . Conclusions Vitamin D deficiency is prevalent among primary and middle school students in Xicheng District, and the 25-(OH)-D levels correlate positively with Hb and SF levels. 25-( OH )-D deficiency may contribute to the development of anemia.
vitamin D ; hemoglobin ; serum ferritin ; primary and middle school student

Objective:To analyze 18F-FDG PET/CT imaging features of non-functional pancreatic neuroendocrine neoplasms (NF-pNENs) and investigate its correlation with pathology and prognosis. Methods:A total of 35 cases (17 males, 18 females; age (51±12) years) of pathologically confirmed NF-pNENs who underwent pretherapeutic 18F-FDG PET/CT from January 2011 to July 2017 in Peking Union Medical College Hospital were retrospectively enrolled. Clinical data were collected and patients were followed up. PET/CT parameters including number and maximum diameter of lesions, SUV max and pancreatic tumor-to-liver ratio (T/L) were measured. Mann-Whitney U test and Kruskal-Wallis rank sum test, Spearman correlation analysis were used to analyze the data. Results:Among the included 35 NF-pNENs patients (G1, n=6; G2, n=21; G3, n=8) with maximum diameter of 3.0(2.1, 6.1) cm and SUV max of 5.5(4.0, 8.9), 32 were positive in PET/CT. There were 1 patient with cystic, 2 with calcification and 3 with dilatation of pancreaticobiliary duct. Among 10 patients with metastases, 8 revealed multiple liver metastases. There was statistical difference of T/L among G1-G3 tumor (1.23(0.60, 2.00), 3.05(1.80, 4.00), 3.90(1.90, 7.60); H=8.29, P=0.016), but there were no statistical differences of SUV max or maximum diameter among G1-G3 tumor ( H values: 4.34, 3.37, P values: 0.114, 0.186). There was a significant correlation between T/L (2.78(1.48, 3.94)) and Ki-67 index (8.0(3.0, 20.0); rs=0.631, P<0.001). Among 27 patients with available follow-up results, T/L in patients with complete remission or stable disease ( n=20) was statistically lower than that in patients with progressive disease or death ( n=7) (2.1(1.2, 3.2) vs 7.5(3.4, 13.4); z=-3.37, P=0.001). Conclusions:18F-FDG PET/CT can detect primary and metastatic lesions of NF-pNENs. T/L can better reflect the proliferative activity based on Ki-67 index than SUV max and it may be favorable on prognostic value.

Objective:To analyze the incidence, biochemical and molecular characteristics, and gene mutation spectrum of neonatal methylmalonic acidemia (MMA) in Shaanxi province.Methods:This study involved 146 152 newborns undergoing neonatal screening for methylmalonic acidemia by tandem mass spectrometry in Northwest Women's and Children's Hospital from January 2014 and December 2019. Clinical manifestations and follow-up data of newborns diagnosed with MMA and their acylcarnitine profiles and gene mutations were analyzed. According to whether they had elevated homocysteine or not, these patients were divided into two groups, the complicated group and the isolated MMA group. The control neonates were those excluded from having methylmalonic acid by re-examination. Kruskal-Wallis and Mann-Whitney U test was conducted for statistical analysis. Results:(1) Twenty-one cases of MMA were confirmed with an incidence of 1/6 960, including 11 cases (52.4%) of isolated MMA (isolated MMA group) and 10 (47.6%) complicated by elevated homocysteine (complicated group). Eight patients in the isolated group had symptoms within one month after birth, mainly feeding difficulties, vomiting, drowsiness, poor response and infection, and five died. Patients in the complicated group were all diagnosed before developing typical clinical symptoms, and no developmental abnormalities were reported during follow-up. (2) Blood propionyl carnitine and its ratios to acetylcarnitine and free carnitine in the isolated MMA and complicated groups were higher than those in the control group [ M (min-max), 9.26 (3.70-37.78) μmol/L and 7.27 μmol/L (3.58-13.62 μmol/L) vs 4.51 μmol/L (1.48-8.69 μmol/L), H=23.239; 1.12 (0.32-2.43) and 0.74 (0.36-1.90) vs 0.25 (0.09-0.45), H=47.061; 0.94 (0.12-1.92) and 0.56 (0.18-1.03) vs 0.17 (0.06-0.38), H=36.868; all P<0.001]. The blood methionine level in the complicated group was significantly lower than that in the isolated MMA group [7.64 μmol/L (3.40-19.25 μmol/L) vs 24.22 μmol/L (10.73-56.55 μmol/L), U=3.000, P<0.001]. (3) All 21 patients carried complex heterozygous mutations or homozygous mutations in pathogenic genes, including 15 distinct MMUT mutations and 13 distinct MMACHC mutations. In the isolated MMA group, the most common mutation was c.323G>A (p.Arg108His) in the MMUT gene with a positive rate of 13.6%, and an unreported mutation, c.1676+11A>G, with unidentified clinical significance, was also found. The most common mutations in the complicated group were c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in the MMACHC gene, and the positive rates were both 20.0%. Moreover, two unreported variants, c.430-2A>C and c.648_650delAGA (p.216_217delSEinsS), were detected and suspected to be pathogenic. Conclusions:MMA is not uncommon in Shaanxi province. Children with isolated MMA tend to be more severe clinically. The identification of hotspot mutations, including c.609G>A (p.Trp203Ter) and c.567dupT (p.Ile190fs) in MMACHC gene and c.323G>A (p.Arg108His) in MMUT gene, provides a foundation for further genetic screening, counseling, and prenatal diagnosis, and is conducive to reduce the mortality and disability rate of neonatal MMA.

The robotic bronchoscopy system is a new technology for lung lesion location, biopsy and interventional therapy. Its safety and effectiveness have been clinically proven. Based on many advanced technologies carried by the robotic bronchoscopy system, it is more intelligent, convenient and stable when clinicians perform bronchoscopy operations. It has higher accuracy and diagnostic rates, and less complications than bronchoscopy with the assistance of magnetic navigation and ordinary bronchoscopy. This article gave a review of the progress of robotic bronchoscopy systems, and a prospect of the combination with artificial intelligence.

Objective:To estimate the effect of comorbid gestational diabetes mellitus (GDM) and depression on glucose metabolism and neonatal morphology.Methods:From March 2015 to October 2018, recruited 18 to 28 weeks pregnant women who met the criteria in the Hefei First People′s Hospital or First Affiliated Hospital of Anhui Medical University or Anhui Maternal and Child Health Hospital, including a total of 4 380 study subjects, of which the birth outcome information of 3 827 newborns were collected. The self-made questionnaire "Maternal Health Questionnaire for Hefei City" and Edinburgh Postpartum Depression Scale were used to obtain basic demographic characteristics and emotional state of depression. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. After delivery, delivery outcome information were collected from the hospital medical records. Covariance analysis was used to analyze the differences in glucose metabolism indicators and neonatal outcome indicators in pregnant women with different GDM and depression status. Multiple logistic regression model was used to analyze the correlation between GDM and depression, with different groups of GDM and depression status (no GDM and depression, simple depression, simple GDM, comorbid GDM and depression)as independent variables and whether they were large for gestational age as dependent variables. The interaction between GDM and depression was also analyzed.Results:The 4 380 pregnant women were (28.8±4.2) years old. The incidence of GDM was 19.5% (852/4 380), and the detection rates of depression in the second and third trimesters were 12.1% (526/4 380) and 12.3% (536/4 367). PG-1h and AUC in the comorbid GDM and depression group were significantly higher than those in the group with no GDM and depression ( P<0.05) and the single GDM group ( P<0.05). After adjusting for factors such as the childbirth age, education level, family′s main economic income, BMI before pregnancy, parity, number of physical activities, and weight gain during pregnancy, compared with the group with no GDM and depression, the RR(95% CI) of LGA occurred in the single depression group, the single GDM group and the comorbid group were 1.31(0.89-1.91), 1.51(1.14-2.00) and 2.43(1.29-4.57), respectively. Further analysis showed that the association between GDM pregnant women with depression and newborn LGA ［ RR (95% CI): 2.12 (1.01-4.49)］ was stronger than that between GDM pregnant women without depression and newborn LGA ［ RR (95% CI): 1.50 (1.12-1.99)］, the P interaction value was<0.05. Conclusion:The status of comorbid GDM and depression can impair glucose metabolism and increase the risk of LGA.

Objective:To estimate the effect of comorbid gestational diabetes mellitus (GDM) and depression on glucose metabolism and neonatal morphology.Methods:From March 2015 to October 2018, recruited 18 to 28 weeks pregnant women who met the criteria in the Hefei First People′s Hospital or First Affiliated Hospital of Anhui Medical University or Anhui Maternal and Child Health Hospital, including a total of 4 380 study subjects, of which the birth outcome information of 3 827 newborns were collected. The self-made questionnaire "Maternal Health Questionnaire for Hefei City" and Edinburgh Postpartum Depression Scale were used to obtain basic demographic characteristics and emotional state of depression. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. After delivery, delivery outcome information were collected from the hospital medical records. Covariance analysis was used to analyze the differences in glucose metabolism indicators and neonatal outcome indicators in pregnant women with different GDM and depression status. Multiple logistic regression model was used to analyze the correlation between GDM and depression, with different groups of GDM and depression status (no GDM and depression, simple depression, simple GDM, comorbid GDM and depression)as independent variables and whether they were large for gestational age as dependent variables. The interaction between GDM and depression was also analyzed.Results:The 4 380 pregnant women were (28.8±4.2) years old. The incidence of GDM was 19.5% (852/4 380), and the detection rates of depression in the second and third trimesters were 12.1% (526/4 380) and 12.3% (536/4 367). PG-1h and AUC in the comorbid GDM and depression group were significantly higher than those in the group with no GDM and depression ( P<0.05) and the single GDM group ( P<0.05). After adjusting for factors such as the childbirth age, education level, family′s main economic income, BMI before pregnancy, parity, number of physical activities, and weight gain during pregnancy, compared with the group with no GDM and depression, the RR(95% CI) of LGA occurred in the single depression group, the single GDM group and the comorbid group were 1.31(0.89-1.91), 1.51(1.14-2.00) and 2.43(1.29-4.57), respectively. Further analysis showed that the association between GDM pregnant women with depression and newborn LGA ［ RR (95% CI): 2.12 (1.01-4.49)］ was stronger than that between GDM pregnant women without depression and newborn LGA ［ RR (95% CI): 1.50 (1.12-1.99)］, the P interaction value was<0.05. Conclusion:The status of comorbid GDM and depression can impair glucose metabolism and increase the risk of LGA.

Objective: To explore the relationship between the vitamin D levels and lipid metabolism during second trimester. Methods: A total of 1 875 pregnant women who were in the second trimester and had antenatal care in 3 hospitals in Hefei of Anhui province from March 2015 to February 2018 were included. Baseline questionnaire survey was performed, and fasting venous blood samples were collected from the pregnant women to detect serum 25(OH)D, cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels. Cubic non-linear model and linear regression model were used to analyze the linear relationship between vitamin D levels and lipid metabolism indicators in the second trimester. Results: The vitamin D deficiency rate was 75.3% (1 412/1 875) in the pregnant women. The mean levels of lipid metabolism indicators TC, TG, HDL-C and LDL-C were (233.22±38.87), (226.24±83.88), (79.04±12.77), and (109.54±25.95) mg/dl respectively. Multivariate linear regression model results showed, compared with Q5 of the 25(OH)D, the TC and TG levels of Q1-Q4 groups significantly increased, and the LDL-C of Q1 and Q2 groups significantly increased. The highest difference between TC, TG and LDL-C was observed in Q1 group. (TC: β=16.88, 95%CI: 10.50-23.26; TG: β=34.92, 95%CI: 21.32-48.53; LDL-C: β=9.06, 95%CI: 4.77-13.35). No significant differences in HDL-C level among the 5 groups were observed. When stratified with vitamin D deficiency the results showed that, when 25(OH)D was <50 nmol/L, TC, TG and LDL-C levels decreased by 3.53 (95%CI: 1.30-5.75), 7.42 (95%CI: 2.41 to 12.44) and 2.08 mg/dl (95%CI: 0.60-3.57) along with a 10 nmol/L increase of 25(OH)D, the difference was statistically significant, and when 25(OH)D was ≥50 nmol/L, no significant correlation was found between 25(OH)D level and TC, TG and LDL-C levels. No significant relationship between 25(OH)D level and HDL-C level was observed regardless of vitamin D deficiency. Conclusions There was a nonlinear relationship between vitamin D levels and lipid metabolism indicators in the second trimester. There was a significant negative correlation between 25(OH)D level and lipid metabolism indicators only in the deficiency of vitamin D.

Objective: To screen the target genes of long non-coding RNA LOC102606465, which was previously identified to be induced by ionizing radiation, in order to examine its potential biological role. Methods: The downstream differentially expressed genes (DEGs) of LOC102606465 were detected by microarray and partially verified by qRT-PCR. GO and KEGG enrichment analysis was performed, and PPI protein interaction network was constructed to screen significant modules and hub genes. Results: The expression of LOC102606465 targeted by siRNA-447 and siRNA-541 was significantly lower than that of siRNA-NC (t=29.095, 13.751, P<0.01). A total of 374 common DEGs were identified(112 up-regulated/262 down-regulated) in both siRNA-447 and siRNA-541. The qRT-PCR was used to validate the expression of DEGs, which was consistent with the microarray result. In GO enrichment analysis, down-regulated DEGs were significantly enriched in " oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor" (molecular function), " basal lamina" (cellular component), " ammonium ion metabolic process" (biological process). Up-regulated DEGs were mainly enriched in " protein phosphatase inhibitor activity" (molecular function), " SNARE complex" (cellular component), " negative regulation of fibrinolysis" (biological process). In addition, the KEGG enrichment analysis revealed that DEGs were significantly enriched in " metabolism of xenobiotics by cytochrome P450" , " dorso-ventral axis formation" , " lysosome glycerophospholipid metabolism" and " p53 signaling pathway" . Based on the STRING database, the PPI network was constructed (including 194 nodes and 268 edges), and one significant module and five key hub genes ACTRT3, CDKN1A, DPYD, TMP4, and PRKACB were identified. Conclusions LOC102606465 could be a potential biomarker for the regulation of ionizing radiation sensitivity, and the down-regulation of LOC102606465 plays an important role in the response to radiation, which would be an important target for regulating radiation sensitivity.

Objective To explore the relationship between different statuses of vitamin D and parathyroid hormone (PTH) during pregnancy with glucose metabolism and the risk of gestational diabetes mellitus (GDM). Methods A total of 4138 pregnant women who had antenatal care in 3 hospitals of Hefei from March 2015 to December 2017 were recruited during 21-24 weeks. Baseline questionnaires were performed and serum 25-hydroxyvitamin D [25(OH) D] and PTH levels were measured in fasting venous blood. Glucose tolerance tests were performed during 24 to 28 weeks. Multivariate linear regression model and multivariate logistic regression model were applied to analyze the differences of glucose metabolism index and GDM risk among pregnant women at different statusesof25(OH)DandPTH.Results Theaveragelevelof25(OH)Dinthesecondtrimesterwas(39.8±16.6) nmol/L, with the median PTH 10.7 (6.9, 16.7) ng/L and the detection rate of GDM 20.4％. Covariance analysis showed no statistically significant association of vitamin D and PTH levels with glucose metabolism indexes. Pregnant women with high PTH and vitamin D deficiency had higher 1h postprandial plasma glucose ( 1hPG) , the area under the glucose curve ( AUCglu ) levels, and GDM risk compared with pregnant women with middle/lower PTH and vitamin D deficiency ( control group, all P<0.05) , and higher PTH accompanied with vitamin D non-deficiency ( Group 2, all P<0.05) . However, significant changes in glucose metabolism indicators and GDM risk were not observed in low-level PTH-pregnant women with vitamin D deficiency ( group 1) and group 2 pregnant women compared with control group. Conclusion There is an interaction between vitamin D/PTH levels and glucose metabolism during pregnancy. Vitamin D deficiency with elevated PTH level is associated with abnormal glucose metabolism.