【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To explore the value of the imaging nomogram model based on preoperative CT features of patients with small intestinal stromal tumor (SIST) in predicting pathological risk classification.Methods:This was a cohort study. The patients who were diagnosed as primary SIST by postoperative pathology in Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to October 2023 were retrospectively included. According to the modified 2008 National Institutes of Health classification criteria, the patients were divided into a pathological intermediate/high-risk group (86 cases) and a very low/low-risk group (56 cases). The features of preoperative enhanced CT images of SIST were analyzed, including tumor boundary, necrosis, intra-tumoral hemorrhage, intra-tumoral calcification, growth pattern, enhancement pattern, enhancement degree, enlarged vessels feeding or draining the mass (EVFDM), and tumor location. Patients were followed up to determine the recurrence-free survival (RFS). Univariate and multivariate logistic regression were used to screen the independent predictors of SIST with pathological medium/high-risk group. The independent predictors were combined to construct an imaging prediction model, and a nomogram was drawn. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the differences in RFS.Results:Univariate logistic regression results showed that tumor shape, necrosis, intra-tumoral hemorrhage, EVFDM, and tumor location were potentially related to medium/high-risk SIST. Multivariate logistic regression results showed that tumor shape ( OR=3.92, 95% CI 1.58-9.71, P=0.003), necrosis ( OR=4.60, 95% CI 1.91-11.09, P<0.001), and EVFDM ( OR=6.25,95% CI 1.74-22.47, P=0.005) were independent predictors of pathological intermediate/high-risk SIST. The area under the curve of the imaging predictive model combining the three predictors to predict the intermediate/high-risk SIST was 0.835 (95% CI 0.769-0.901), the sensitivity was 0.810, the specificity was 0.839, and the accuracy was 0.789. Taking the cut-off value (0.810) as the boundary value, the patients were divided into the high-risk group (74 cases) and the low-risk group (68 cases) according to the prediction results. The median RFS of the predicted high-risk group was poorer than that of the predicted low-risk group, and the difference was statistically significant ( χ2=5.20, P=0.023). Conclusions:The imaging nomogram model based on preoperative CT image features shape, necrosis, and EVFDM can effectively predict the pathological intermediate/high-risk SIST before surgery and has important predictive value for postoperative recurrence.

Objective:To explore the effect of different concentrations of Chinese herbal formula,Er-miao-san(EMS)immune regulatory gene on Gnαq expression in rats with collagen-induced arthritis(CIA).Methods:In the study,we established a CIA model,and randomly divided into model groups,EMS group with 1.5,3.0 and 4.5 g/kg(L-EMS,M-EMS,H-EMS)were adminis-tered to CIA rats by gavage,methotrexate was used as a positive control group(MTX).The rats in each group were given correspond-ing drugs for treatment,and the normal control group and model group were given the same amount of normal saline gavage.ELISA detects the expression of IL-1β,IL-6 and TNF-α in rats'serum.The mRNA and protein expression of Gnαq were analyzed using qRT-PCR and Western blot.The localization of Gnαq was performed by IHC.Results:The joint of rats in CIA group showed obvious damage,tissue hyperplasia and inflammatory infiltration;the joint tissue destruction and proliferation of MTX and EMS groups were reduced;the expressions of IL-1β,IL-6 and TNF-α in CIA group were extremely increased(P<0.01).The expressions of IL-1β(except H-EMS group),IL-6 and TNF-α in MTX and EMS groups were significantly lower than those in CIA group(P<0.05).The expressions of IL-1β,IL-6 and TNF-α in L-EMS group were lower than those in the M-EMS and H-EMS groups(P<0.05,P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of CIA group were higher than those of Control group(P<0.01).The expression of Gnαq mRNA and protein in spleen and joints of EMS and MTX groups were lower than those of CIA group(P<0.05).The expression of Gnαq mRNA and protein in the dose of 1.5 g/kg of EMS group was lower than those of the other groups(P<0.01,P<0.05).Different degree of posi-tive signal was detected in spleen and joints in different groups.Conclusion:Gnαq is expressed in spleen and joints of CIA rats,may participate in the formation of inflammatory response in CIA rats,and then mediate the formation and development of RA by down-reg-ulating the expression of Gnαq.

Objective:To develop an Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses and test its reliability and validity.Methods:Based on the theory of knowledge, attitude, and practice, a preliminary scale draft was formed through a literature review, three rounds of Delphi expert consultation, and a pre-survey. Using convenience sampling, 311 hemodialysis nurses were selected for a survey from December 2022 to February 2023 for item analysis, exploratory factor analysis and reliability testing. Another survey was conducted on 260 hemodialysis nurses from February to June 2023 for confirmatory factor analysis, convergent validity, and discriminant validity testing.Results:The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses included three subscales and five dimensions, with a total of 33 items. The content validity index at the item level was 0.867 to 1.000, and the content validity index at the scale level was 0.992. After exploratory factor analysis, two, one, and two common factors were extracted from the knowledge, attitude, and practice subscales, with cumulative variance contribution rates of 70.114%, 75.192%, and 67.467%, respectively.Confirmatory:factor analysis showed that the model fitted well. The Cronbach's α coefficients of the three subscales were 0.929 to 0.943, the half reliability coefficients were 0.861 to 0.903, and the retest reliability coefficients were 0.824 to 0.874. Conclusions The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses has good reliability and validity and can be used to evaluate the physical examination ability of hemodialysis nurses for arteriovenous fistula.

Objective:To analyze the changes in the retinal and choroidal microvascular structures in the macular region of patients with acute central serous chorioretinopathy (CSC), as well as the influencing factors of subretinal fluid (SRF) volume.Methods:A prospective selection of 37 patients with monocular acute CSC diagnosed by ophthalmology examination at the Xi ′an First Hospital from January to October 2023 was conducted. The affected eye group was Group A, and the contralateral eye was Group B. The right eye of 30 age and gender matched normal individuals during the same period was selected as the normal eye group (group C). The scanning frequency source optical coherence tomography (SS-OCTA) was used to scan the macular area of the tested eye within a range of 6 mm×6 mm. We analyzed and recorded the vascular density (VD), perfusion area (PA), retinal thickness (RT), choroidal thickness (CT), as well as choroidal vascular volume (CVV) and choroidal vascular index (CVI) of the superficial and deep retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) in the macular area of 0-1 mm, 0-3 mm, and 0-6 mm using our own software. At the same time, we recorded the volume of SRF in the affected eye group. We compared the changes in VD, PA, RT, CT, CVV, and CVI among three groups. The Spearman rank correlation test was used to analyze the correlation between SRF volume and microvascular structural parameters.Results:(1) There was no statistically significant difference in VD and PA of SCP between the affected eye group and the contralateral eye group within the range of 0-6 mm in the macular area (all P>0.05); The VD and PA of SCP in the affected eye group and the contralateral eye group were lower than those in the normal eye group, and the differences were statistically significant (all P<0.05); The VD and PA of DCP in the affected eye group were lower than those in the contralateral eye group, and the difference was statistically significant (all P<0.05). Within the range of 0-3 mm in the macular area, the VD and PA of DCP in the affected eye group and the contralateral eye group were lower than those in the normal eye group, and the differences were statistically significant (all P<0.05). The RT of the affected eye group was higher than that of the contralateral eye group, and the RT of the contralateral eye group was higher than that of the normal eye group, with statistical significance (all P<0.05). (2) Within the range of 0-6 mm in the macular area, the CT of the affected eye group was higher than that of the contralateral eye group, and the CT of the contralateral eye group was higher than that of the normal eye group, with statistical significance (all P<0.05). There was no statistically significant difference in the CVV and CVI of the choroidal vessels between the affected eye group and the contralateral eye group (all P>0.05); The CVV and CVI of the choroidal vessels in the affected eye group and the contralateral eye group were higher than those in the normal eye group, and the differences were statistically significant (all P<0.05). (3) The volume of SRF is negatively correlated with the VD of DCP within the range of 0-3 mm in the macular area ( P<0.05), and positively correlated with CT within the range of 0-6 mm ( P<0.05). Conclusions:Acute CSC is a binocular choroidal disease, and choroidal thickening is mainly due to the thickening of the large and medium vascular layers; Acute CSC can cause a decrease in superficial and deep retinal blood flow density in the macular region; The volume of SRF is negatively correlated with the VD of DCP and positively correlated with CT.

Objective To investigate the pathological and magnetic resonance imaging (MRI) characteristics of orbital diffuse large B-cell lymphoma (DLBCL). Methods A total of 48 patients with orbital DLBCL were selected via a retrospective case-control study in the orbital DLBCL group, and 51 patients with DLBCL of primary central nervous system during the same period were included in primary DLBCL group. The clinical characteristics and MRI features of the orbital DLBCL group were analyzed, and the pathological characteristics and peripheral blood platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were compared between the two groups. Results The main clinical manifestations of orbital DLBCL patients included local orbital mass in 48 cases (100.00%), limited ocular motility in 38 cases (79.17%), exophthalmos in 33 cases (68.75%), decreased visual acuity in 25 cases (52.08%), diplopia in 17 cases (35.42%), and epistaxis in 9 cases (18.75%). Orbital DLBCL predominantly occurred in the extraconal space (54.17%), with lesions mostly located above the orbit (52.08%). T1-weighted images mainly showed intermediate signal intensity (60.42%), T2-weighted images mainly showed intermediate (56.25%) and high signal intensity (29.17%), diffusion-weighted images mainly showed high signal intensity (58.33%), and apparent diffusion coefficient maps mainly showed low signal intensity (60.42%). There were no statistically significant differences in histopathological subtype, CD20 positive expression, CD79a positive expression, CD45RO positive expression, International Prognostic Index score, and pathological stage between the two groups (P>0.05). The PLR in the orbital DLBCL group was higher, while NLR and LMR were lower than that in the primary DLBCL group (P < 0.05). Conclusion Orbital DLBCL exhibits specific clinical manifestations and MRI characteristics. MRI can serve as the primary diagnostic tool, and its combination with pathological immunohistochemical analysis and peripheral blood PLR, NLR, and LMR test results can improve the accuracy and timeliness of diagnosis.

Objective:To observe the clinical characteristics and optical coherence tomography (OCT) features of pseudopapilledema (PPE) combined with peripapillary hyper-reflective ovoid mass-like structures (PHOMS) in children.Methods:A retrospective observational study. From October 2019 to May 2021, total 22 eyes from 12 children diagnosed as PPE combined with PHOMS in the Neuro-ophthalmology Department of The First Hospital of Xi’an (Affiliated of The First Hospital of Northwest University) were recruited. Among the children, 6 were male and 6 were female. The average age was (10.6±2.7) years. The average course from disease onset to diagnosis of PPE combined with PHOMS was (8.0±7.5) months. All patients underwent best corrected visual acuity (BCVA), relative afferent papillary defect (RAPD), Ishihara's test, fundus photography, OCT, fundus autofluorescence (FAF), ocular B-mode ultrasound, visual field and patternvisual evoked potential (P-VEP). The clinical and OCT characteristics of the patients were observed.Results:The anterior segments of the patients were normal. The intraocular pressures and Ishihara's test were all normal. All RAPD were negative. Total 22 eyes, BCVA was 1.0 in 21 eyes and one eye was 0.12. The fundus photography revealed blurred optic discs margin, showing mild to moderate edema-like elevation with more prominent in the nasal parts, presenting as a "C" shape halo. No obvious abnormal fluorescence was observed in FAF. The OCT scan of involvement eyes showed an elevated appearance in vary degrees, and the sharply marginated ovoid hyper-reflective mass-like structures which laterally herniated into the peripapillary region under retinal nerve fiber layer and above the Bruch membrane were detected with consecutive nasal enlargement scanning, corresponding to the nasal parts in the fundus photography. The higher degree of elevation, the larger the volume. Macular retina pigment epithelium layer and ganglion cell thickness were normal. Ocular B-mode ultrasound showed that the head of the optic nerve in the posterior wall of the eyeball (in front of the optic disc) was elevated in all affected eyes, and there was no strong signal echo in it. Visual field examination showed physical blind spot enlargement in 3 eyes and visual field defect in 2 eyes. P-VEP examination showed that the peak was slightly delayed in 3 eyes and the amplitude was slightly reduced in 3 eyes.Conclusions:Enlarged nasal optic disc OCT scan can improve the detection rate of PHOMS. PHOMS were detected bilaterally in the cases with binocular PPE while only in the effected eye in the cases of monocular PPE; the higher degree of PPE, the lager volume of PHOMS. PHOMS were could contribute to the diagnosis of PPE in children.

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.
Humans ; Child ; Female ; Abnormalities, Multiple ; Blood Group Antigens ; Family ; Malformations of Cortical Development/genetics* ; Brain ; Mutation

Objective To investigate the effect and mechanism of Liuling Jiedu Pills on acute pharyngitis caused by Staphylococcus aureus in rats.Methods The rat model of acute pharyngitis was replicated using the method of injecting 1×109 CFU·mL-1 of Staphylococcus aureus solution into the pharynx of rats.SD rats were randomly divided into a blank group,a model group,a Lanqin Oral Solution group(5 mL·kg-1),and a low-,medium-,and high-dose group of Liuling Jiedu Pills(4.375,8.750,and 17.500 mg·kg-1),with 10 rats in each group.Rats in each group were administered the drug by gavage once a day for 7 days.The general conditions of the rats were observed and recorded every day during the modeling and drug administration periods,and the local inflammation in the pharynx was scored;histopathological changes in the pharynx of the rats were observed by hematoxylin-eosin(HE)staining;serum interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor α(TNF-α),and tumor necrosis factor-α(TNF-α)were detected by ELISA.Immunohistochemistry and Western Blot were used to detect the protein expression levels of IL-1β,IL-6 and TNF-α in rat pharyngeal tissue.Results Compared with the blank group,rats in the model group had significantly increased pharyngeal erythema,significantly higher inflammation scores(P＜0.01),significantly lower body mass on days 5-7 after modeling(P＜0.05,P＜0.01),significantly higher pathological scores(P＜0.01),significantly higher levels of the serum inflammatory factors IL-1β,IL-6,and TNF-α(P＜0.01),and significantly higher pharyngeal tissues showed significantly higher levels of IL-1β,IL-6,and TNF-α proteins(P＜0.01).Compared with the model group,the pharyngeal erythema was significantly reduced in the Lanqin Oral Solution group and the low-,medium-and high-dose groups of Liuling Jiedu Pills,and the inflammation scores were significantly reduced(P＜0.01),and the serum levels of IL-1β,IL-6,and TNF-α were significantly reduced(P＜0.01);the body mass of the rats in the Lanqin Oral Solution group,and in the medium-and high-dose groups of Liuling Jiedu Pills,were significantly increased on the seventh day of the modeling(P＜0.01);the histopathological scores and the levels of IL-1β,IL-6 and TNF-α proteins in pharyngeal tissue were significantly decreased(P＜0.05,P＜0.01).Conclusion Liuling Jiedu Pills can significantly improve the symptoms and inflammatory pathological changes of pharyngeal tissues in rats with acute pharyngitis,and its mechanism may be related to the down-regulation of the expression levels of inflammatory factors such as IL-1β,IL-6,and TNF-α.

Objective:To evaluate the short-term efficacy and the improvement of quality of life of enzyme replacement therapy (ERT) with Imiglucerase on children with Gaucher disease(GD) through the same time monitoring.Methods:Six children diagnosed as GD who were treated by ERT with Imiglucerase in the Department of Hematology of the Children′s Hospital of Shanxi Province from May 2019 to May 2020 were recruited.Every 3 months, the sizes of the liver and spleen was palpated, the change of bone pain was recorded, and the haematological index was examed.The volumes of the liver and spleen at 1-year treatment were measured by CT.Bone involvement was examined by magnetic resonance imaging (MRI). In addition, the body weight, height, and the 36-Item Short Form Survey (SF-36) were measured and compared with pre-treatment levels.These data were analyzed statistically by SPSS 25.0 and the difference between pretherapy and post-treatment was compared by paired t test. Results:Six children diagnosed as GD received ERT with Imiglucerase.No adverse events were reported.Decreased volumes of the liver and spleen, and increased hemoglobin level and platelet count were detected after 3-6 months of ERT.After 1 year of ERT, hemoglobin level significantly increased compared with pre-treatment level ( t=4.200, P=0.008). Although the platelet count increased at 1-year ERT, it was comparable with pre-treatment level ( t=2.260, P=0.073). The volumes of liver and spleen decreased by (22.10±15.28)% ( t=2.725, P=0.042) and (47.10±18.42)% ( t=3.162, P=0.034) after 1 year of ERT, respectively.During the first year of ERT, the height and weight increased (6.17±2.86) cm ( t=5.286, P=0.003) and (4.08±2.01) kg ( t=4.975, P=0.004), respectively.SF-36 score increased significantly from (489.35±103.99) points to (632.75±73.34) points ( t=5.740, P=0.002). After 1 year of ERT, 1 patient still had bone pain, and 2 cases were worse in bone MRI, which may be attributed to the short period of follow-up and insufficient dose, and another 3 had no change in bone MRI. Conclusions:ERT ameliorates GD-associated anemia, organomegaly and growth retardation, and improves the growth rate of body mass and height and the quality of life in the short period.However, short-term ERT does not improve the bone disease.