ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Blinding is an important method to control the measure bias in clinical trials.As a complex and invasive intervention,acupuncture has more difficulty in blinding implementation compared to drugs and has a higher risk of unblinding breakage.This article provides an overview of the blinding in acupuncture clinical study and summarized the key aspects,including:there is no standard for the application and reporting of sham acupuncture design and blinding measures,appropriate sham acupuncture devices still need to be developed,currently there are no effective methods of operator blinding,blinding assessment has not been given due attention,sham acupuncture design should be standardized and reported.Researchers should conduct further studies to address critical questions and challenges to provide methodological support to improve and promote the quality of acupuncture clinical research.

Objective:To explore the clinical manifestations and pathogenic variant in a family with epilepsy, developmental delay and brain deformity.Methods:Clinical data of the child and his family members who had visited the Department of Pediatrics, Linyi People's Hospital on July 2, 2022 were collected. The child, his sister and parents were subjected to high-throughput sequencing, and the result was verified by Sanger sequencing.Results:The child was a 6-year-old boy with developmentally delay and had epileptic seizures with fever sensitivity for four years. Cranial imaging showed brain dysplasia, while the video electroencephalogram showed abnormal discharge. High-throughput sequencing showed the child has harbored a heterozygous c. 5G>T (p.Arg2Leu) variant of TUBB2A gene, which was unreported previously. His sister also carried the variant and had similar clinical manifestations, whilst his parents were of the wild-type and had normal clinical phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+ PM2_Supporting+ PM5+ PP1+ PP2+ PP3). Conclusion:The heterozygous c. 5G>T (p.Arg2Leu) variant of the TUBB2A gene, in the form of gonadal mosaicism, probably underlay the disorders in this family.

Objective:To explore the clinical features and genetic etiology of a child with Baraitser-Winter syndrome (BWS).Methods:A BWS child who had sought medical attention at the Linyi People′s Hospital on April 8, 2022 was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples were obtained from the child and his parents. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 5-year-and-6-month-old male, had typical clinical features of BWS including congenital non-myogenic ptosis, arched eyebrows, wide philtrum, and pointed chin. Neurological symptoms included microcephaly, developmental delay, epilepsy, and deafness. Cranial MRI revealed enlarged frontal lobes, decreased white matter, and hydrocephalus. WES has identified a heterozygous c. 430G>A (p.Asn144Tyr) missense variant in the ACTG1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP3_Moderate+ PP4). Conclusion:The heterozygous c. 430G>A (p.Asn144Tyr) missense variant of the ACTG1 gene probably underlay the pathogenesis of BWS in this child. Above finding has enriched the mutation spectrum of BWS-related genes and provided a basis for clinical diagnosis and genetic counseling.

In recent years, the number of people living in short-term and long-term period in high-altitude has been continuously increasing, with over 81.6 million people living in areas with an altitude of ≥ 2, [KG*9]500 meters. In China, there are over 10 million people who frequently reside at high altitudes, and over 20 million people enter the plateau every year. The unique plateau climate has triggered a series of plateau related diseases, among which high altitude cerebral edema (HACE) is one of the most serious diseases. If patients are not treated promptly and appropriately, they may die from cerebral hernia within 24 hours. However, the exact mechanism of the development of HACE is not fully understood, which makes the clinical prevention and treatment of HACE challenging. Mesenchymal stem cells (MSC) and their exosomes (MSC-Exos) have the ability to repair damaged tissues and cells, resist oxidative stress, inhibit inflammatory reactions, and regulate autophagy, which may potentially become new drugs for preventing and treating HACE. This article elucidated the pathogenesis of high altitude brain edema and the potential roles of MSC and MSC-Exos based on relevant literatureat home and abroad, providing a theoretical basis for the prevention and treatment of HACE by MSC and MSC-Exos.

Objective: To investigate the influencing factors and population attributable risk percent (PAR%) of low back pain in automobile assemblers. Methods: A total of 634 assemblers from 11 automobile manufacturers in Shiyan City, Hubei Province were chosen as research subjects using judgment sampling method. The prevalence of low back pain in the past one year was investigated using Musculoskeletal Disorders Questionnaire. PAR% was used to analyze the contribution of influencing factors to low back pain. Results: The annual prevalence of low back pain was 68.8%. The results of multivariate logistics regression showed that length of service>15 years, high school or secondary college education or above, standing most of the time, sitting most of the time, the proportion of cumulative time of poor posture in work shift time ≥1/8, and bending for insufficient height of working space were the risk factors for low back pain (all P<0.05). The PAR% of the proportion of cumulative time of poor posture in work shift time ≥1/8 was 43.0%, 37.8% for standing most of the time, and 12.8% for bending for insufficient height of working space. Conclusion: The annual prevalence of low back pain was higher in automobile assemblers. The influencing factors included individual factors and occupational factors. The proportion of cumulative time of poor posture in work shift time ≥1/8, standing most of the time and bending for insufficient height of working space should be taken as the priority intervention factors to reduce the prevalence of low back pain among assemblers in this enterprise.

Objective:To analyze the clinical phenotype and gene sequencing results of a child with hyperekplexia, and to clarify her genetic etiology.Methods:The clinical information of the child was collected, and the whole exome sequencing of the child and her parents was performed. The suspected pathogenic variants were verified by Sanger sequencing and bioinformatics analysis.Results:There was a 12 years old girl, who was hospitalized in the Department of Pediatric Neurology of Linyi People′s Hospital because of "paroxysmal limb stiffness for more than 11 years and aggravated for half a month" on July 4, 2022. The girl showed exaggerated startle reflexes and generalized siffness in response to external sudden, unexpected stimuli, occasionally accompanied by apnea and cyanosis, frequent attacks occurred several times a day, lasting for 1-30 minutes, and early head and abdomen flexion can be relieved. She showed normal growth and development, no abnormality in brain magnetic resonance imaging and video electroencephalogram during seizure. The whole exome sequencing showed that there was a missense heterozygous mutation c.643T>C(p.W215R) in the SLC6A5 gene of the child. Neither of the parents carried this mutation, which was a novel and de novo variant. According to the guidelines of American College of Medical Genetics and Genomics, this variant was a likely pathogenic variant [PS2: de novo (both maternity and paternity confirmed) in the patient with the disease and no family history; PM2: undetected variants in the normal population; PP3: multiple softwares predicted that this mutation would have harmful effects on genes or gene products], and highly conserved. Swiss modeling found that the hydrogen bond of the modified amino acid also changed. Conclusions:Hyperekplexia is relatively rare and prone to misdiagnosis. The main clinical features are excessive startle reflexes (limb shaking, or jumping) to unexpected external stimuli, resulting in overall stiffness, normal growth and development, and normal video electroencephalogram during the seizure. The likely pathogenic heterozygous missense variant c.643T>C (p.W215R) of SLC6A5 gene is the genetic cause of this case.

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

Background Previous research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. Objective To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. Methods We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. Results The average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL⁻¹. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL⁻¹), perfluorooctanoic acid (PFOA, 4.55 ng·mL⁻¹), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL⁻¹), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL⁻¹), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL⁻¹), perfluorobutanoic acid (PFBA, 1.81 ng·mL⁻¹), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL⁻¹), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL⁻¹) were higher than 1.00 ng·mL⁻¹. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L⁻¹ and 0.24 (95%CI: 0.18, 0.30) mmol·L⁻¹, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50^th to the 75^th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L⁻¹, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. Conclusion PFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents. METHODS: A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci. RESULTS: The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor. CONCLUSION The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.
Humans ; Female ; Child ; Pregnancy ; Child, Preschool ; Muscle Hypotonia/genetics* ; Prenatal Diagnosis ; Computational Biology ; Epileptic Syndromes ; Facies