OBJECTIVE: To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. METHODS: A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using "SETD1B" and "epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. RESULTS: The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely c.5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+PM2_Supporting+PP2+PP3). The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no significant difference in incidence between males and females. CONCLUSION SETD1B gene variants may cause neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.
Humans ; Female ; Child ; Epilepsy/genetics* ; Language Development Disorders/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Exome Sequencing ; Male

Objective:To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. Methods:A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using " SETD1B" and " epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. Results:① The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. ② WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely, c. 5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). ③ The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. ④ A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no statistically significant difference in incidence between males and females. Conclusion:SETD1B gene variant may induced neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.

Objective:To explore the clinical features and genetic etiology of a child with a SETD1B gene variant causing seizures and language delay. Methods:A child with a SETD1B gene variant admitted to the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University in September 2022 was selected as the study subject. Clinical data of the child were collected, and peripheral blood samples from the child and her parents were obtained. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variant. Using " SETD1B" and " epilepsy" as the Chinese and English keywords, relevant cases were retrieved from databases including CNKI, Wanfang Data, OMIM and PubMed, with the search period spanning from database inception to June 2024. Results:① The child was a 6-year-old female presenting with myoclonic seizures accompanied by global developmental delay. ② WES and Sanger sequencing revealed that the child has carried a de novo SETD1B gene variant, namely, c. 5582G>A (p.Cys1961Tyr). According to the American College of Medical Genetics and Genomics (ACMG) guidelines for sequence variant interpretation, this variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). ③ The child was not controlled with effective doses of valproate, levetiracetam, or clonazepam but was successfully managed with low-dose lamotrigine. Follow-up electroencephalography showed normal results, and developmental progress gradually improved. ④ A total of 37 epilepsy cases with SETD1B gene variants were reported across six studies. The predominant seizure types included absence seizures and myoclonic absence seizures, accompanied by delayed language development. The response to pharmacological treatment was generally poor, with no statistically significant difference in incidence between males and females. Conclusion:SETD1B gene variant may induced neurological disorders with drug-resistant epilepsy and severe clinical manifestations. Lamotrigine is effective in controlling the epileptic seizures.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

OBJECTIVE：To investigate the effec ts of angiotensin receptor neprilysin inhibitor （ARNI）sacubitril valsartan sodium（SVS）on the short-term prognosis of patients with acute anterior myocardial infarction （AAMI）complicated with acute cardiac insufficiency. METHODS ：A total of 80 patients with AAMI and Killip grade Ⅱ-Ⅳ of cardiac function ，who met the inclusion criteria ，were randomly divided into ARNI group and control group ，with 40 patients in each group. Both groups were given the same basic standardized drug treatment ，vital signs support treatment and percutaneous coronary intervention treatment at the same time. On this basis ，ARNI group was given SVS tablet orally ，with initial dose of 25 mg each time ，twice a day ； thereafter，gradually adjust the dose to 200 mg each time ，twice a day. Control group was given Enalapril maleate tablets orally ， with an initial dose of 5 mg each time ，twice a day ；thereafter，gradually adjust the dose to 10 mg each time ，twice a day. Both groups took medicine for a long time ，and were followed up after 1，3 and 6 months of medication to the clinic. The levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth stimulation expressed gene 2 protein （sST2） and echocardiography indexes were compared between 2 groups before and after medication. The 6-minute walking test （6MWT）and the incidence of cardiogenic readmission events were recorded in 2 groups after medication. RESULTS ：Compared with before treatment，the indexes of the two groups were significantly improved at 1，3 and 6 months after treatment （P＜0.05）. Compared with control group ，the levels of NT-proBNP and sST 2 in ARNI group decreased significantly （P＜0.05），the levels of left ventricular ejection fraction and 6MWT increased significantly（P＜0.05），and the left ventricular end systolic diameter and left ventricular end diastolic diameter decreased significantly，after 3 and 6 months of treatm ent（P＜0.05）. However ，there was no significant difference in the velocity ratio of peak E to peak A ，pulmonary artery pressure ，right ventricular end diastolic diameter and the incidence of cardiogenic readmission events between 2 groups（P＞0.05）. CONCLUSIONS ：For patients with AAMI complicated with acute cardiac insufficiency ， compared with enalapril ，SVS can significantly improve the cardiac function （especially the left ventricular systolic function ）， reduce the inflammatory reaction of cardiomyocytes ，protect cardiomyocytes ，so as to improve the short-term prognosis of patients.

Objective:To study the incidence and classification of chromosomal abnormalities in villi of missed abortion patients with assisted reproductive technology (ART) and natural conception (NC).Methods:Totally 637 patients with missed abortion villi from the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University during January 2016 and January 2020 were collected and divided into ART group and NC group according to the mode of pregnancy in this retrospective cohort study. The ART group was further divided into artificial insemination by husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Next generation sequencing (NGS) was used to detect the copy number variations (CNVs) and chromosome number abnormalities of chorionic villi of missed abortion. Results:Among 637 missed abortion chorionic villi, 45.2% (288/637) of the samples had normal chromosome and 54.8% (349/637) had abnormal chromosome. CNVs accounted for 3.8% (14/637) of the total samples, and chromosome number abnormalities accounted for 52.5% (335/637) of the total samples. The abnormal rates of villi chromosome in ART group and NC group were 59.2% (226/382) and 51.0% (130/255), respectively, and there was no significant difference between ART group and NC group ( P>0.05). The abnormal rates of villus chromosome in AIH group, IVF group and ICSI group were 52.1% (25/48), 58.9% (146/248) and 64.0% (55/86), respectively. Compared with NC group, the abnormal rate of villus chromosome in IVF group and ICSI group was increased, but there was no significant difference ( P>0.008). Conclusion:In general, ART did not increase the incidence of chromosomal abnormalities in missed abortion villi. However, compared with natural pregnancy and AIH assisted pregnancy, IVF/ICSI had a higher chromosomal abnormality in missed abortion villi.

Objective:To study the incidence and classification of chromosomal abnormalities in villi of missed abortion patients with assisted reproductive technology (ART) and natural conception (NC).Methods:Totally 637 patients with missed abortion villi from the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University during January 2016 and January 2020 were collected and divided into ART group and NC group according to the mode of pregnancy in this retrospective cohort study. The ART group was further divided into artificial insemination by husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Next generation sequencing (NGS) was used to detect the copy number variations (CNVs) and chromosome number abnormalities of chorionic villi of missed abortion. Results:Among 637 missed abortion chorionic villi, 45.2% (288/637) of the samples had normal chromosome and 54.8% (349/637) had abnormal chromosome. CNVs accounted for 3.8% (14/637) of the total samples, and chromosome number abnormalities accounted for 52.5% (335/637) of the total samples. The abnormal rates of villi chromosome in ART group and NC group were 59.2% (226/382) and 51.0% (130/255), respectively, and there was no significant difference between ART group and NC group ( P>0.05). The abnormal rates of villus chromosome in AIH group, IVF group and ICSI group were 52.1% (25/48), 58.9% (146/248) and 64.0% (55/86), respectively. Compared with NC group, the abnormal rate of villus chromosome in IVF group and ICSI group was increased, but there was no significant difference ( P>0.008). Conclusion:In general, ART did not increase the incidence of chromosomal abnormalities in missed abortion villi. However, compared with natural pregnancy and AIH assisted pregnancy, IVF/ICSI had a higher chromosomal abnormality in missed abortion villi.

OBJECTIVETo observe the effect difference between acupuncture of "five needles therapy" and conventional acupuncture for asthma of latent cold phlegm-fluid in the lung.

METHODSTwo hundred and ten cases were randomly assigned into an observation group and a control group, 105 cases in each one. Finally 7 cases were dropped out in the observation group; 6 cases in the control group. Feishu (BL 13), Dazhui (GV 14), Fengmen (BL 12) were used in the observation group; conventional acupuncture was used in the control group, and the main acupoints were Feishu (BL 13), Zhongfu (LU 1), Tiantu (CV 22), Danzhong (CV 17), Kongzui (LU 6), Dingchuan (EX-B 1), Fenglong (ST 40), Fengmen (BL 12), Taiyuan (LU 9). The needles were retained for 30 min each time, once a day for continuous 12 days. The scores of the individual symptoms and signs were observed before treatment and on the 3rd, 6th, 9th, 12th days, including pant, cough, cough up phlegm, fullness and oppression in the chest and diaphragm, wheezing rale and shortness of breath. The clinical effects were compared between the two groups.

RESULTSThe scores of six individual symptoms and signs on the 3rd, 6th, 9th, and 12th days in the two groups were lower than those before treatment (all<0.05), except the score of wheezing rale in the control group on the 3rd day (>0.05). The scores of pant, wheezing rale, cough on the 3rd, 6th, 9th, and 12th days in the observation group were lower than those in the control group (all<0.05), except the score of wheezing rale score on the 3rd day (>0.05). There were no significant difference between the two groups about the scores of cough up phlegm, fullness and oppression in the chest and diaphragm and shortness of breath on the 3rd, 6th, 9th, and 12th days (all>0.05), except the score of fullness and oppression in the chest and diaphragm in the observation group was lower than that in the control group on the 12th day (<0.05). 46 cases were clinical cured, 39 cases were markedly effective, 10 cases were effective and 3 cases were ineffective in the observation group with the total effective rate of 96.9%. 23 cases were clinical cured, 43 cases were markedly effective, 24 cases were effective and 9 cases were ineffective in the control group with the total effective rate of 90.9%. The difference was statistical (<0.05).

CONCLUSION"Five needles therapy" has significant therapeutic effect for asthma of latent cold phlegm-fluid in the lung, which is better than conventional acupuncture.

The student problems existing in the practice and training course of acupuncture-moxibustion treatment include unsolid basic knowledge, inexperienced basic skills and poor comprehensive utilization ability. The writers proposed the effective countermeasures accordingly. Firstly, the students are required to go over the related knowledge in advance, targeting the weakness, and complement the basic knowledge. Secondly, the teachers provide the demonstration and guidance for the practice to improve the basic skills. Thirdly, the clinical simulation is adopted for the comprehensive training to enhance the comprehensive utilization ability. The countermeasures mentioned above improve effectively the basic skills and comprehensive ability in the students and lay the foundation for the future clinical work.