Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective: To determine the otorhinolaryngologic manifestations of long COVID-19 infection among patients consulting at the Quezon City General Hospital. : Methods Design: Cross-Sectional Study Setting: Tertiary Government Hospital Participants: Patients aged 18 years old and above, who previously tested positive for the SARS-COV-2 Test, and consulted with otolaryngologic problems at the Outpatient department, Emergency Room, or were dmitted, or referred from other services to the Department of Otorhinolaryngology Head and Neck Surgery, from October 2022 to January 2023 were considered for inclusion. Results: Out of 150 participants, 127 (84.67%) reported having otorhinolaryngologic symptoms. Five percent (5%) had ongoing symptomatic COVID-19 (4 to 12 weeks) and 11% had post COVID-19 syndrome (>12 weeks). Patients with long COVID-19 had rhinorrhea (54.51%), hyposmia (51.47%), dysgeusia (48.9%), anosmia (48.53%), sore throat (47.8%), ageusia (29.78%), tinnitus (23.53%), ear pain (23.53%), phantosmia (21.33%), and dizziness (11.76%). Out of 25 patients with long COVID, only 2 had pneumonia and 1 was hospitalized and eventually recovered. Conclusion This study showed a prevalence rate of 16% of long COVID-19 with rhinorrhea as the most prominent symptom. Long-term monitoring is essential and patients who had COVID should be advised to report any lingering illness which may subsequently develop. Physicians should be vigilant and aware of the clinical manifestations of long COVID in order to institute proper intervention.
COVID-19 ; SARS-CoV-2 ; Long COVID ; Post-Acute COVID-19 Syndrome ; Long Haul COVID-19 ; Post-Acute COVID-19 Syndrome ; Rhinorrhea

Objective:To understand the identification value of pointing gestures in children with autism spectrum disorder(ASD) and its relationship with functional development.Methods:From December 2020 to November 2021, 1 099 children from Children’s Health Care Center of Beijing Children’s Hospital were tested by pointing gestures test, including 942 ASD children and 157 typical developed children.And the data of children's neuropsychological development scale from 800 children aged 1.0-5.9 were collected.SPSS 20.0 was used for statistical analysis. Trend test was used to analyze the distribution of pointing gestures test sensitivity in autistic children, and ANOVA was used to analyze the relationship between pointing gestures test scores and functional development fields.Results:The sensitivity of pointing gestures was 83.5% in children aged 1.0-10.0 years, 76.3%-93.1% in children aged 1.0-4.9 years, and 93.1%-95.1% in children aged 1.0-2.9.With the increase of age, the sensitivity of pointing gestures in autistic children (linear-by-linear association =164.889, P<0.001) and the Yoden index had a decreasing trend. The positive predictive value (91.53%-100.00%) and negative predictive value (75.36%-91.84%) were found in the children aged 1.0-10.0 years.The sensitivity of pointing gestures test was 44.9% in children with mild autism aged 1.0-10.0 years and 46.5%-65.9% in children with mild autism aged from 1.0-3.9 years. The sensitivity of pointing gestures test was 81.5% in children with moderate autism aged from 1.0-10.0 years and 87.3%-97.8% in children with moderate autism aged 1.0-3.9 years. The sensitivity of the pointing gestures test was 97.2% in children with severe autism aged 1.0-10.0 years, and 100.0% in children with severe autism aged 1.0-3.9 years. The sensitivity of the pointing gestures in mild, moderate and severe autism children decreased with age (linear-by-linear association values were 16.725, 64.232, 66.732 respectively, all P<0.001). The children with severe autism mainly scored 2 points (80.3%, 419/522) on the pointing gestures test , and children with moderate autism mainly scored 1 point(64.2%, 170/265) on the pointing gestures test. There were significant differences in functional development among different pointing gestures test groups.Functional development score in the autism children with 0 score of pointing gestures test was significantly higher than those with 1 score and 2 scores of pointing gestures test (all P<0.05). Conclusion:Pointing gestures has good sensitivity in children with autism (especially 1.0-4.9 years of age), and may serve as an objectively observable screening method. The better children with autism score on the pointing gestures, the better their functional development.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective:To investigate the effects of lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) on proliferation, invasion and tumorigenic ability of colorectal cancer SW620 cells.Methods:SW620 cells cultured in vitro were divided into empty vector group (transfected with pcDNA3.1 empty vector plasmid), MVIH overexpression group (transfected with pcDNA3.1-MVIH overexpression vector plasmid), NC siRNA group (transfected with interference sequence negative control NC siRNA) and MVIH siRNA group (transfected with MVIH siRNA interference sequence). The mRNA expression level of MVIH in SW620 cells in each group was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), clone formation test and transwell chamber were used to detect the proliferation activity, clone formation ability and invasion ability of SW620 cells; The subcutaneous transplanted tumor of nude mice was constructed by subcutaneous injection of SW620 cells in each group 48 hours after transfection. The transplanted tumor volume was measured every 5 days to evaluate the tumor growth. On the 25th day, the nude mice in each group were killed and the tumor weight was measured. Results:The mRNA MVIH expression level, cell proliferation, clone formation rate and number of invasive cells of SW620 cells in the MVIH overexpression group were significantly higher than those in the empty vector group ( P<0.05); the MVIH mRNA expression level, cell proliferation , clone formation rate and number of invasive cells of SW620 cells in the MVIH-siRNA group were significantly lower than those in NC-siRNA group ( P<0.05). The results of subcutaneous transplantation tumor in nude mice showed that the growth rate of tumor in MVIH overexpression group was faster and the tumor weight was higher than those in the empty vector group ( P<0.05); the growth rate of tumor in MVIH overexpression group was slower and the tumor weight was lower than those in NC-siRNA group ( P<0.05). Conclusions:LncRNA MVIH can promote the proliferation, invasion and tumorigenesis of SW620 cells in colorectal cancer.

Objective:To investigate the correlation between social and linguistic parenting behaviors and developing capability of children with autism.Methods:From August 2020 to December 2020, the social and linguistic parenting behaviors of 302 parents of children diagnosed with autism were investigated in the outpatient department of the hospital.Meanwhile, the data of Gesell scale for children, the social life competence scale for infant and junior middle school students, the autism behavior checklist and the Cancy autism behavior scale were collected.SPSS 20.0 software was used for statistical analysis.Independent sample t test and analysis of variance were used to compare the social and linguistic parenting behaviors of different parents.Pearson correlation analysis was used to analyze the correlation between the social and linguistic parenting behaviors of parents and children's developmental ability and symptom severity. Results:There were no statistically significant differences in children's social and language development parenting behavior between father and mother ( t=1.033, P=0.303; t=-0.312, P=0.756). There were no statistically significant differences in children's social and linguistic parenting behaviors between fathers of different age groups ( F=1.425, P=0.244; F=1.127, P=0.345). Among mothers of different age groups, the social parenting behaviors of <30 years old and 30-34 years old groups were significantly better than those of 35-39 years old group ( F=3.374, P=0.019; LSD: P=0.010, P=0.006). Among fathers, the social parenting behavior( F=4.346, P=0.008; LSD: P=0.020, P=0.001) and social + linguistic parenting behavior in the graduate group and college group were significantly better than those in the high school/vocational group( F=3.965, P=0.012; LSD: P=0.020, P=0.002). Among mothers, the social parenting behavior ( F=2.812, P=0.040; LSD: P=0.008, P=0.023, P=0.009), linguistic parenting behavior ( F=3.769, P=0.011; LSD: P=0.010, P=0.025, P=0.001), social + linguistic parenting behavior ( F=3.654, P=0.013; LSD: P=0.005, P=0.015, P=0.002) in graduate and above groups were significantly better than those in college group, high school/vocational group, junior high school and below groups.The scores of social parenting behavior(40.72±6.80), linguistic parenting behavior(27.20±5.22), and social + linguistic parenting behavior(67.92±11.10) were significantly correlated with children’s fine motor(61.75±16.41)( r=0.193, P=0.001; r=0.153, P=0.009; r=0.190, P=0.001), cognition(68.28±16.83)( r=0.231, P=0.000; r=0.186, P=0.001; r=0.229, P=0.000), language(53.01±18.55) ( r=0.262, P=0.000; r=0.305, P=0.000; r=0.304, P=0.000) and social self-care(61.44±17.85) ( r=0.264, P=0.000; r=0.238, P=0.000; r=0.274, P=0.000). The scores of linguistic parenting behavior and social + linguistic parenting behavior were correlated with children's social life ability (8.65±0.89) ( r=0.142, P=0.046; r=0.140, P=0.049). There was no significant correlation between social parenting behavior, linguistic parenting behavior, social + linguistic parenting behavior and the scores of ABC scale (50.53±21.39) ( r=-0.089, P=0.336; r=-0.115, P=0.215; r=-0.107, P=0.250) and CABS scale (13.96±4.54) ( r=-0.050, P=0.490; r=-0.059, P=0.411; r=-0.058, P=0.421). Conclusions:The social and linguistic parenting behaviors are related to their age and educational level, and are significantly correlated to developing capability of children with autism, but have nothing to do with the severity of children's symptoms.

OBJECTIVE: To present a case of progressive hemifacial atrophy in a young woman with Parry-Romberg Syndrome and the role of autologous fat transfer to improve her aesthetic appearance and lessen facial asymmetry.

METHODS:

Design:           Case Report

Setting:           Tertiary Government Training Hospital

Patient:           One

RESULTS: A 20-year old woman consulted because of drooping of the right eyelid and gradual thinning of right cheek muscles since age 16.  On examination, the right facial muscles were hypoplastic with prominent facial bony ridges. An MRI scan showed atrophy of the right medial pterygoid and masseter. She underwent autologous fat transfer on the right side of the face to augment the cheek, improve cosmetic appearance and lessen facial asymmetry.  

Conclusion: Our patient is satisfied and happy with the outcome and cosmetic appearance of her autologous fat transfer and is ready to undergo the same procedure if the need arises in the future. Although no definite cure exists for Parry Romberg syndrome, our report illustrates the role of autologous fat transfer as an inexpensive, easily harvested and biocompatible material to improve facial asymmetry. The procedure yielded encouraging results, although long-term benefits remain uncertain.

Keywords: Parry-Romberg syndrome; progressive hemifacial atrophy; autologous transplantation

Objective To investigate the correlation between serum hepcidin level and iron, mineral metabolism in maintenance hemodialysis (MHD) patients. Methods Seventy-five MHD patients were selected. The serum hepcidin, serum iron and mineral metabolism indexes were detected by enzyme-linked immunosorbent double antibody sandwich method, and their correlation was analyzed. Results The level of serum hepcidin in 75 MHD patients was 87- 264 μg/L. The patients were divided into 3 groups according to serum hepcidin level. In group A, the serum hepcidin level of 26 cases was＜120 μg/L; in group B, the serum hepcidin level of 24 cases was 120- 200 μg/L; in group C, the serum hepcidin level of 25 cases was>200 μg/L. There were no significant differences in age, gender, albumin and serum calcium among 3 groups (P > 0.05). The levels of ferritin, transferrin saturation (TS), serum phosphorus and parathyroid hormone (PTH) increased in the 3 groups as the hepcidin level increased, while hemoglobin, serum iron, total iron binding capacity (TIBC), and 25 hydroxy vitamin D decreased significantly, and there were statistical differences (P＜0.05). The Pearson correlation analysis result showed that serum hepcidin was positively correlated with ferritin, PTH, serum phosphorus (r = 0.862, 0.536 and 0.320; P＜0.01); and serum hepcidin was negative correlation with serum iron, TIBC, hemoglobin, 25 hydroxy vitamin D (r=-0.358,-0.270,-0.284 and-0.614; P＜0.01); but there was no correlation between serum hepcidin and albumin and serum calcium (r=0.018 and-0.005, P＞0.05). Conclusions The serum hepcidin level in MHD patients is closely related to iron and mineral metabolism.

Objective To explore the application effects of three-dimensional teaching mode for clinical anesthesiology. Methods 43 students were selected into control group, who were from class one, grade 2010 in the Department of Anesthesiology, Ningxia Medical University. 42 students were selected into observation group, who were from class two, grade 2010 in the Department of Anesthesiology, Ningxia Medical University. The traditional teaching mode were used for the students in control group during the teaching of clinical anesthesiology, while three-dimensional teaching mode were used for the students in observation group during the teaching. At the end of teaching, the teaching results were compared between the control group and the observation group, mainly including the usual scores evaluated from an anaesthesia plan plus an anaesthesia case discussion, and the final scores. The teaching satisfaction questionnaire were used to assess the effects of two teaching methods on the students' interest in learning, the capacity of clin-ical practice, the abilities of exploring, analyzing and solving problems, etc. SPSS 17.0 software was used in statistical analysis. The students' teaching results were tested by using two independent samples t-test. The satisfactions of these teaching effects were tested by using the Chi-square test. Results The usual and final scores in the observation group were significantly higher than those in the control group [(88.1±5.1) vs. (75.3±4.2), (82.1±3.3) vs. (75.7±3.9); P<0.05]. Compared with the control group, the satisfactions of teaching effects in the observation group were higher such as to stimulate interest in learning (60.5% vs. 90.5%), to improve the abilities of self-study (30.2% vs. 83.3%) and clinical practice (51.2% vs. 85.7%), to widen the scope of knowledge (46.5% vs. 88.1%) and to cultivate the spirits of innovation (55.8% vs. 83.3%), etc (P<0.05). Conclusion During the teaching of clinical anesthesiology, the three-dimensional teaching mode has more advantages than the traditional one, which is good for improving the students' innovation and practice abilities.