In recent years， the research data on the combination model of insomnia of liver depression and qi stagnation syndrome in traditional Chinese medicine （TCM） were sorted out and summarized in terms of the selection of experimental animals， modelling methods， and model evaluation， with a view to providing references for the standardized preparation of the experimental model of insomnia of liver depression and qi stagnation syndrome and the study of the intervention mechanism. As for the selection of experimental animals， rats and mice are commonly used for the study of sleep patterns in the insomnia model of liver depression and qi stagnation syndrome because their sleep patterns are similar to those of human beings； zebrafish is suitable for the study of sleep patterns in early development because of its high genetic homology； and rhesus macaques， common marmosets， and crab-eating monkeys are used for the study of highly complex sleep disorders because their physiological and behavioural characteristics are closer to those of human beings. In terms of modelling methods， electrical stimulation， chronic restraint， chronic emotional stress and impact psychological stress each have their own characteristics and application scenarios， while chronic tail-clamping stimulation combined with intraperitoneal injection of p-chlorophenylalanine （PCPA） combines physical and chemical stimuli， in order to simulate the complex mechanism of insomnia in human beings， and to more comprehensively simulate the pathology of insomnia with liver depression and qi stagnation syndrome. In terms of evaluation indexes， electroencephalography （EEG） and electromyography （EMG） monitoring and barbiturate synergistic sleep test are the most commonly used and scientific methods for evaluating insomnia animal models with liver depression and qi stagnation syndrome， which can provide intuitive and continuous sleep state monitoring； barbiturate synergistic sleep test can reflect the sensitivity and responsiveness of the model animals to the sleep-regulating medications； and the introduction of the method of using formulas to measure syndromes for the evaluating the model can combine the treatment and diagnostic principles of TCM with modern scientific research.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective:To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14.Methods:A child who had presented at the Henan Provincial People′s Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis.Results:The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c. 1609G>A (p.V537M) in exon 17 and c. 802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+ PP3+ PP4). Conclusion:The c. 1609G>A (p.V537M) and c. 802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.

Objective To observe the RNA expression level of carbohydrate thiotransferase family(CHSTs)in non-functioning adenoma,and to analyze its clinical significance.Methods Ninety tissue samples of clinical non-functioning adenoma were collected.The mRNA expression levels of CHST1/2/7/8,follicle-stimulating hormone subunit(3(FSHb),POU domain transcription factor 1(POU1F1)and steroid-producing factor 1(SF-1)were detected by real time fluorescence quantitative PCR(RT-qPCR).And receiver operating characteristic(ROC)curve was used to screen the CHST molecule possessing the function for diagnosing CHST molecule differentiated by non-functional adenoma lineage.Results The expression amounts of CHST1 gene and CHST7 gene in the tumors with large volume were higher than those with small tumors(P=0.014,P=0.044),and the CHST2 gene level in female patients was higher than that in male patients(P=0.016),and the CHST8 gene level in invasive tumors were lower than in non-invasive tumors(P=0.044).The grouping was conducted according to the intensity of SF-1 staining,there were statistically signif-icant differences in CHST1/2/7/8 gene levels among all groups(P＜0.05);the grouping was performed ac-cording to the intensity of PIT1 staining,there were statistically significant differences in CHST1/7 gene levels among all groups(P＜0.01).The correlation analysis showed that the CHST1 level was positively correlated with the tumor volume and POU1F1 level(r=0.322,P=0.002;r=0.686,P＜0.001)and negatively corre-lated with the NR5A1 level(r=-0.227,P=0.032).The CHST7 level was positively correlated with the POU1F1 level(r=0.774,P＜0.001);the CHST8 level was positively correlated with the FSHb and NR5A1 levels(r=0.485,P＜0.001;r=0.725,P＜0.001).The area under ROC curve(AUC)of CHST1 for diagno-sing the immature POU1F1 lineage was 0.750(P=0.023).AUC of CHST8 for diagnosing SF-1 lineage was 0.776(P=0.008),and the AUC of CHST1 combined with CHST8 was 0.823(P=0.002).Conclusion The CHST family is involved in the proliferation and differentiation of clinical nonfunctional adenomas.CHST1 combined with CHST8 is valuable in the diagnosis of SF-1 lineage differentiation.

Objective:To study the clinical and genetic characteristics of Wiskott-Aldrich syndrome (WAS) in neonates.Methods:From January 2016 to August 2022, neonates with WAS admitted to the neonatal department of our hospital were studied.Their clinical features, laboratory findings, genetic characteristics and clinical outcomes were retrospectively analyzed.Results:A total of 11 neonates(all male) were included. The mothers of 3 neonates had thrombocytopenia during pregnancy. The presenting symptoms included isolated bloody stool (4 cases), jaundice (3 cases), bloody stool with petechiae, bloody stool with hematemesis, cough and fever(1 case each). Eczema appeared from 6 d to 3 months after birth and in 6 cases during the neonatal period. None of the 11 cases had serious infection during the neonatal period. 9 cases had infection from 8 d to 5 months and 2 cases had not been infected until the last follow-up. Genetic sequencing showed four frameshift variants(c.30dupC, c.205dupT, c.1340_1343dupC and c.673_674delA), four nonsense variants(c.37C>T, c.295C>T, c.889C>T and c.823G>T) and three missense variants(c.134C>T, c.397G>A and c.341T>C). Pedigree verification of variants found 10 cases were inherited from their mothers and 1 case was de novo variant.Conclusions:WAS is characterized by bloody stool and eczema in the neonatal period, mostly without serious infections and lacking specific manifestations. Genetic screening for early identification of unexplained thrombocytopenia in male newborns should be performed as early as possible.

ObjectiveTo explore the efficacy of acupuncture intervention for children with monocular refractive-parallax amblyopia and the possible mechanisms of brain function based on resting-state functional magnetic resonance （rs-fMRI）. MethodsSeventy-six children with anisometropic amblyopia were randomly divided into routine treatment group （38 cases） and acupuncture treatment group （38 cases）. In the conventional group， the children were given three regular treatments of red flash， grating and visual stimulation for 5 mins each time； in the acupuncture group， on the basis of the conventional treatment， the children were given acupuncture for 20 mins each time on bilateral Jingming （BL 1）， Cuanzhu （BL 2）， Guangming （GB 37） and Fengchi （GB 20）； the children in both groups were treated once every other day and three times a week for 4 weeks. The corrected visual acuity was compared between groups before and after treatment. Fifteen children with left-sided refractive amblyopia were randomly selected from each of the above two groups and underwent brain rs-fMRI scans before and after treatment， and 10 healthy children with normal visual acuity of the matched gender and age were included in the normal group and underwent brain rs-fMRI scans. Based on the activation likelihood estimation （ALE） method， we constructed the what visual pathway network， and compared and analyzed the spherical regions of interest （ROIs） of the children with normal children， and both groups of children with differences in functional connectivity （FC values） within the what pathway in the brain before and after treatment. ResultsTwo cases dropout in the acupuncture group， and finally 36 cases in the acupuncture group and 38 cases in the conventional group were included in the analysis. Compared with before treatment， the best corrected visual acuity of amblyopia in both groups was significantly improved after treatment （P＜0.05）， and the improvement of vision in the acupuncture group was significantly better than that in the conventional group （P＜0.05）. The results of rs-fMRI showed that the FC values of the primary optic cortex and the right fusiform gyrus， the left lingual gyrus and the right fusiform gyrus， and the right infraoccipital gyrus and the right middle temporal gyrus were significantly elevated in the brain of the refractive amblyopia children with the whitepathic amblyopia， compared with that of the normal children （P＜0.05）. The FC values of the left lingual gyrus， the right suboccipital gyrus with the right fusiform gyrus， the left lingual gyrus with the right middle temporal gyrus， the right and left lateral middle occipital gyrus， and the right and left lateral middle occipital gyrus with the right suboccipital gyrus were significantly （P＜0.05） lower in the conventional group compared with those in the conventional group before treatment. Compared with that before acupuncture treatment， the FC values of the right lingual gyrus and the right fusiform gyrus， the primary visual cortex and the right middle temporal gyrus increased significantly after acupuncture treatment （P＜0.05）， and the FC values of the left inferior occipital gyrus and the right middle temporal gyrus， the FC values of the left lingual gyrus and the right middle occipital gyrus decreased significantly （P＜0.05）. Compared between groups after treatment， the FC between the left suboccipital gyrus and the right fusiform gyrus in the acupuncture group was significantly higher than that in the conventional group （P＜0.05）， and the FC between the left middle occipital gyrus and the right and left suboccipital gyrus was significantly lower than that in the conventional group （P＜0.05）. ConclusionAcupuncture can significantly improve the corrected vision of anisometropic amblyopic children， and its effect mechanism may focus on regulating the occipito-temporal interlobular functional connectivity within the what pathway， thus improving the children's visual function of shape and color vision and visual learning and memory ability.

Objective : A convolutional neural network (CNN) model was established to automatically analyze flow cytometry (FCM) data to achieve the preliminary diagnosis of acute myeloid leukemia(AML) , and explore the feasibility of applying CNN model to FCM data analysis. Methods : The exploratory study of CNN application was carried out using the bone marrow FCM data obtained by the FlowRepository database and the Clinical Testing Center of Xinjiang Uygur Autonomous Region People ′ s Hospital , and the data had been clinically confirmed whether AML was present. Among them , the public data was divided into training sets , validation sets and test sets according to 6 ∶ 2 ∶ 2 , and local data was used for external test; In order to adapt the FCM data to the CNN model , an FCM data structure based on the image matrix principle was proposed , and after preprocessing the original data , the variables related to the preliminary diagnosis of AML were extracted , including sidescattered light and the expression levels of CD45 , CD13 , CD33 , HLA⁃DR , CD117 , CD34 , and each variable was written into the matrix. Cell sampling and data augmentation methods were used to increase the sample size of the training set , the keras software package was used to build the LeNet⁃5 CNN model in Python , and the training set and the validation set were used for model training and parameter tuning respectively to evaluate the performance of the model on the test set. Results : The accuracy of CNN to identify AML on the two test sets was 0. 931 , 0. 851 , the sensitivity was 0. 667 , 0. 636 , the specificity was 0. 968 , 0. 940 , and the area under the receiver operating characteristic curve was 0. 940 and 0. 917. Conclusion Based on the proposed FCM data structure , the CNN model can realize the preliminary diagnosis of AML , indicating that CNN has certain application value in FCM data analysis.

The treatment of locally advanced rectal cancer (LARC) is extremely challenging, and it is difficult to achieve satisfactory results with surgical resection alone. In recent years, the diagnosis and treatment of LARC tends to be multi-disciplinary (MDT) mode. The emerging neoadjuvant treatment strategy is a milestone. At present, the preferred treatment for LARC is neoadjuvant chemoradiotherapy combined with total mesorectal excision. This article summarizes the main treatments of LARC neoadjuvant therapy, hoping to provide reference for clinical diagnosis and treatment.

Objective:To study the clinical and laboratory characteristics of neonatal isolated sulfite oxidase deficiency (ISOD).Methods:An infant with neonatal ISOD admitted to our hospital was retrospectively analyzed. Using key words "isolated sulfite oxidase deficiency", "SUOX gene", "Infant, newborn", databases including CNKI, Wanfang database, National library and literature center of science and technology, China science paper online, PubMed, Web of Science and EMBASE (up to January 2021) were searched and literature review was conducted. The clinical manifestations, laboratory results, treatment and prognosis were analyzed.Results:Our patient was a full-term male infant with eye movement disorder, refractory seizures, feeding difficulties, increased muscle tone, developmental retardation and microcephaly. Urine sulfite paper-strip test was positive. Uric acid was normal. Whole exon sequencing (WES) revealed SUOX c.475G>T and c.1201A>G compound heterozygous mutations. Cranial MRI showed multiple encephalomalacia and brain atrophy at 5-month of age. The infant died at 8-month. In the literature review, a total of 29 articles and 32 cases of neonatal ISOD were found. 87.5% of the cases developed symptoms within 1-week after birth. All had convulsive seizures. Some of them had feeding difficulties, muscle tone changes, developmental retardation, microcephaly and ectopia lentis. Cranial imaging showed white matter cystic lesions and brain atrophy. Laboratory examination showed elevated urinary sulfite and S-sulfocysteine. Uric acid and xanthine/hypoxanthine were normal. Blood homocysteine was decreased. 23 cases received genetic testing and all of them had SUOX mutations. The treatment was mainly symptomatic relief and supportive treatment. During follow-up, 15 cases died, 13 cases survived and 4 cases were unknown. All the surviving children had drug-resistant convulsions and developmental retardation.Conclusions:Neonatal ISOD may present with refractory convulsions, feeding difficulties and developmental retardation. Cystic white matter changes and brain atrophy may be seen on cranial imaging. Elevated urinary sulfites, decreased blood homocysteine and normal uric acid are important clues for diagnosis. Genetic testing is helpful for early diagnosis.

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Female ; Heterozygote ; Humans ; Isovaleryl-CoA Dehydrogenase/genetics* ; Male ; Mutation