Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To assess the intervention effect of nicotinamide mononucleotide (NMN) on the mouse model of hematotoxicity induced by subacute benzene exposure. Methods Benzene exposure and NMN intervention were adopted in a 2×2 factorial design, as benzene exposure and non-exposure, and NMN intervention and non-intervention. Male specific pathogen-free C57BL/6J mice were randomly assigned to negative control group, NMN control group, simple benzene exposure group and NMN intervention group, with 12 mice in each group. Benzene exposure of mice in simple benzene exposure group and NMN intervention group was conducted by dynamic inhalation of benzene at a concentration of 325 mg/m³ for six hours per day, five days per week for four weeks (28 days). Mice in the negative control and NMN control group inhaled clean air. During benzene exposure, mice in the NMN control group and NMN intervention group received NMN in drinking water at a dose of 300 mg/kg body weight. Peripheral blood samples of mice were collected for complete blood count analysis and calculation of composite inflammatory indices after 28 days. Results Interaction analysis showed that the counts of peripheral white blood cell, neutrophil, lymphocyte, and platelet of mice in the simple benzene exposure group were lower than those in the negative control group (all P<0.05). Neutrophil and platelet counts in the NMN intervention group were higher than those in the simple benzene exposure group (all P<0.05). The results of main effect analysis showed that the monocyte count of peripheral blood, systemic inflammatory index, systemic inflammatory response index, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio of mice in the benzene exposure group increased (all P<0.05), and the basophil count and lymphocyte/monocyte ratio decreased (all P<0.05), compared with the control group. Conclusion Oral NMN alleviates subacute benzene-induced decreases in peripheral neutrophil and platelet counts in mice. This protective effect may be related to the targeted intervention of NMN on mitochondrial energy metabolism disorder and oxidative damage induced by benzene exposure in male mice.

Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

Objective To investigate the effects of five-element music on depressive behaviors and intestinal flora in offspring of fear-stress rats during pregnancy.Methods Thirty-six 0.5-day pregnant Wistar rats were divided randomly into a control group,fear-stress group,and five-element music group,and the subsequent litters continued the maternal grouping.Pregnant rats in the fear-stress and five-element music groups were modeled on days 1～19 of gestation using the bystander electric method,while the five-element music group was also exposed to Feather Tune five-element music intervention.The fear behavior and serum glucocorticoid(GC)levels in pregnant rats were assessed on day 20 of pregnancy by open field test and enzyme-linked immunosorbent assay,respectively,to evaluate the effectiveness of the model.Depression in 3-week-old offspring was evaluated by open field,tail suspension,and sucrose preference tests.Norepinephrine(NE),dopamine(DA),and 5-hydroxytryptamine(5-HT)levels in the hippocampus of the offspring were measured by high-performance liquid chromatography.Changes in the intestinal flora of the offspring were analyzed by 16S rRNA sequencing.Expression levels of the proximal colonic proteins claudin1,occludin,and ZO1 in the offspring were measured by Western blot assay.Results Pregnant rats in the fear-stress group stayed longer in the area around the open field(P＜0.05),had fewer entries into the central area(P＜0.001),and had higher serum GC levels compared with those in the blank group(P＜0.001).In contrast,five-element music exposure reversed these behavioral changes(P＜0.05)and serum GC levels(P＜0.001)in the fear-stress group.Offspring in the fear-stress group exhibited decreased open-field crossing frequency(P＜0.01),reduced sucrose preference index,and longer immobility time in the tail suspension test(P＜0.05),compared with those in the blank group,together with significantly decreased NE,DA,and 5-HT levels in the hippocampus(P＜0.05).Rats in the fear-stress group showed decreased diversity of the intestinal flora(P＜0.01)and significant alterations in flora structure,including higher abundance of Proteobacteria,Enterobacteriaceae,Enterococcus,and Escherichia(P＜0.05),and lower abundance of Spirochaetes,Spirochaetaceae,Lachnospiraceae,Ruminococcaceae,Treponema,Prevotella,Coprococcus,Allobaculum,Ruminococcus,and Dorea(P＜0.05).The proximal colonic proteins Claudin1,Occludin,and ZO1 were significantly downregulated(P＜0.05).The open-field crossing frequency,sucrose preference index,and duration of tail suspension immobilization were improved in the five-element music group compared with those in the fear-stress group(P＜0.05),while DA and 5-HT levels were significantly restored in the hippocampus(P＜0.05),species diversity of the intestinal flora increased(P＜0.01)and changes in the abundance of the flora were reversed,and the proximal colonic proteins Occludin and ZO1 expression were significantly upregulated(P＜0.05).Conclusions Five-element music intervention during pregnancy can ameliorate fear-stress-induced depression behaviors and intestinal flora disorders in the offspring.

Objective To conduct bibliometrics and visual analysis of local benign paroxysmal positional verti-go(BPPV)research in the past 20 years for further basic and clinical research in the future.Methods We collected the journal articles on BPPV published between January 1,2004 and December 31,2023 from the databases of CNKI,Wanfang,VIP and Web of Science Core Collection.Multidimensional measurement and visual analysis were carried out using bibliometrics software to identify the research hotspots and new trends in this field,and to deter-mine the cooperation and influence among authors,institutions and journals.Results A total of 717 Chinese papers and 212 SCI papers were utilized for the analysis.The literature in this field gradually increased at an average annual growth rate of 12.8％,among which the Journal of Clinical Otolaryngology Head and Neck Surgery published the most articles(n=167),followed by the Chinese Journal of Otology(n=94)and the Journal of Audiology and Speech Pathology(n=76).The journal with the largest number of SCI publications is Frontiers in Neurology(n=44).In terms of authors and institutions,Zhuang Jianhua published the most Chinese papers,Yang Xu published the most SCI papers,and Shanghai Jiaotong University published the earliest and most SCI papers in this field(n=21).The main research keywords in this realm in recent years involve video head pulse test,vestibular migraine,re-sidual symptoms,residual dizziness and anxiety.The keywords retaining burst intensity to 2023 include video head pulse test,residual dizziness,children,anxiety,and residual symptoms.Conclusion Video head impulse test,re-sidual dizziness,children,anxiety and other aspects are critical areas of ongoing research in BPPV.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

OBJECTIVES: To investigate the impact of prenatal fear stress on placental amino acid transport and emotion and cognition development in offspring rats. METHODS: Thirty pregnant Wistar rats were randomized equally into control and fear stress (induced using an observational foot shock model) groups. In each group, placental and serum samples were collected from 6 dams on gestational day 20, and the remaining rats delivered naturally and the offspring rats were raised under the same conditions until 8 weeks of age. Emotional and cognitive outcomes of the offspring rats were assessed with behavioral tests, and placental structure was examined using HE staining. Bioinformatics analysis was used to identify differentially expressed placental transporter genes under fear stress. The expressions of system A and system L amino acid transporters, along with other specialized transporters, were detected using qRT-PCR and Western blotting. Fetal serum amino acid concentrations were determined by HPLC. The correlations between fetal amino acid levels and behavioral outcomes of the offspring rats were analyzed. RESULTS: The dams with fear stress showed reduced open-field activity and increased freezing behavior with significantly decreased placental weight, fetal weight, and fetal-to-placental ratio. Bioinformatics analysis revealed 28 differentially expressed transporter genes involved mainly in amino acid transport. In the fear stress group, fetal serum amino acid levels were significantly lowered and Slc38a1, Slc43a1, Slc43a2, Slc7a8, Slc6a6, Slc1a1 and Slc6a9 mRNA and protein expressions were all downregulated. The offspring rats in fear stress group exhibited decreased novel object preference and spontaneous alternation with reduced open arm exploration and increased immobility in emotional tests. Lower early-life amino acid levels was found to correlate with impaired adult cognition. CONCLUSIONS Prenatal fear stress in rats impairs placental amino acid transporter expression and reduces fetal serum amino acid levels, potentially contributing to long-term cognitive deficits in the offspring rats.
Animals ; Female ; Pregnancy ; Placenta/metabolism* ; Fear ; Rats ; Rats, Wistar ; Cognition ; Prenatal Exposure Delayed Effects ; Stress, Psychological ; Amino Acids/blood* ; Amino Acid Transport Systems/metabolism*

Objective:To carry out carrier screening among people of childbearing age, detect the pathogenic genes of monogenic genetic diseases and analyze the carrier status of pathogenic variants, so as to provide fertility guidance and intervention measures for high-risk families.Methods:From August 2022 to August 2023, 1 533 families of childbearing age who met the criteria were recruited in the Chinese PLA General Hospital, including a total of 3 044 subjects. According to the standard enrollment procedure, 223 genes (197 autosomal recessive genes and 26 X-linked genes) of the subjects were tested. According to the screening results, genetic counseling and fertility guidance were provided to the subjects. Invasive prenatal diagnosis was performed for high-risk couples (both couples being carriers of the same autosomal recessive disease gene or the woman was a carrier of X-linked disease gene), and their pregnancy pattern, outcome and offspring phenotype were followed up.Results:(1) A total of 3 044 cases from 1 511 couples and women of childbearing age from 22 families were included for carrier screening. Totally 1 503 families chose simultaneous screening and 30 families chose sequential screening out of the 1 533 families. Among the 3 044 subjects, 1 603 individuals carried at least one pathogenic or likely pathogenic variant, and the overall carrier rate was 52.66% (1 603/3 044). A total of 2 292 pathogenic or likely pathogenic variants were detected, and 0.75 variants (2 292/3 044) were detected per capita. (2) The three genes with the highest carrier rates were GJB2 (8.67%, 264/3 044), CYP21A2 (3.19%, 97/3 044) and PAH (3.09%, 94/3 044). There were 32 genes with a carrier rate ≥1/200, 17 genes with a carrier rate ≥1/100, and 7 genes with a carrier rate ≥1/50. (3) Thirty-eight high-risk families were identified. After excluding G6PD gene mutation, there were 33 high-risk families, of which 25 couples were carriers of the same autosomal recessive gene, 9 women were carriers of X-linked gene, and 1 family was double high-risk couple with both autosomal recessive and X-linked gene. After further excluding the GJB2 c.109G>A mutation, 21 high-risk families were identified. Preimplantation genetic testing for monogenic disease was performed in 12 families after genetic counseling. Prenatal diagnosis was completed in 4 out of 5 high-risk families who conceived naturally. Two fetuses carried the parental variants and terminated the pregnancy, one fetus did not carry the parental variants but was induced due to trisomy 21 syndrome, and one fetus was a carrier of congenital disorders of glycosylation type 1a.Conclusions:Carrier screening effectively identifies high-risk genetic disease families and provides reproductive guidance to prevent the birth of affected children. However, establishing multidisciplinary team is essential for managing complex cases. Implementation should prioritize prenatal institutions with genetic counseling or diagnostic expertise for monogenic disorders or established referral networks.

Objective To observe the value of C-arm CT stent precision technology in intracranial arterial stent implantation.Methods Data of 38 patients with symptomatic intracranial atherosclerotic stenosis who underwent intracranial arterial stent implantation were retrospectively analyzed.Stent displayed in 2D-digital subtraction angiography(DSA)during and immediately after implantation were observed,and superselective C-arm CT scanning of target artery and stent precision reconstruction were performed.Subjective scoring of display stent structure in 2D-DSA and stent precision reconstruction images were comparatively analyzed,and the clarity rate of displaying stent and detection rate of related complications were compared.Results Totally 45 stents were implanted in 38 patients.In 2D-DSA,the subjective score was 0 of 1,1 of 20 and 2 of 24 stents,respectively.Stent precision reconstruction image showed that subjective score was 0 of 1 stent and was 3 of 44 stents.The clarity rate of displaying stent in stent precision reconstruction image was 97.78％(44/45),much higher than that of 2D-DSA image(0[0/45],P＜0.001).Among 44 stents displayed in 2D-DSA,poor stent opening and abnormal perforator vessel was observed in each 1 stent,and no clear abnormality was found in the rest stents.Among 44 stents revealed in stent precision reconstruction images,poor stent opening,thromboses in stent and stent mesh protruding into vascular lumen were found each in 2 stents,while perforator vessel spasm and localized stenosis after stent implantation were noticed in 3 stents.Arterial dissection occurred in 8 stents during balloon dilation,after timely implantation of a new stent,stent precision reconstruction images showed the dissection rupture was completely covered.The complications of stent precision reconstruction was higher than that of 2D-DSA(38.64％[17/44]vs.4.55％[2/44].P=0.002).Conclusion C-arm CT stent precision technique had obvious advantages for intracranial artery stent implantation.

Objective To investigate the effects of five-element music on depressive behaviors and intestinal flora in offspring of fear-stress rats during pregnancy.Methods Thirty-six 0.5-day pregnant Wistar rats were divided randomly into a control group,fear-stress group,and five-element music group,and the subsequent litters continued the maternal grouping.Pregnant rats in the fear-stress and five-element music groups were modeled on days 1～19 of gestation using the bystander electric method,while the five-element music group was also exposed to Feather Tune five-element music intervention.The fear behavior and serum glucocorticoid(GC)levels in pregnant rats were assessed on day 20 of pregnancy by open field test and enzyme-linked immunosorbent assay,respectively,to evaluate the effectiveness of the model.Depression in 3-week-old offspring was evaluated by open field,tail suspension,and sucrose preference tests.Norepinephrine(NE),dopamine(DA),and 5-hydroxytryptamine(5-HT)levels in the hippocampus of the offspring were measured by high-performance liquid chromatography.Changes in the intestinal flora of the offspring were analyzed by 16S rRNA sequencing.Expression levels of the proximal colonic proteins claudin1,occludin,and ZO1 in the offspring were measured by Western blot assay.Results Pregnant rats in the fear-stress group stayed longer in the area around the open field(P＜0.05),had fewer entries into the central area(P＜0.001),and had higher serum GC levels compared with those in the blank group(P＜0.001).In contrast,five-element music exposure reversed these behavioral changes(P＜0.05)and serum GC levels(P＜0.001)in the fear-stress group.Offspring in the fear-stress group exhibited decreased open-field crossing frequency(P＜0.01),reduced sucrose preference index,and longer immobility time in the tail suspension test(P＜0.05),compared with those in the blank group,together with significantly decreased NE,DA,and 5-HT levels in the hippocampus(P＜0.05).Rats in the fear-stress group showed decreased diversity of the intestinal flora(P＜0.01)and significant alterations in flora structure,including higher abundance of Proteobacteria,Enterobacteriaceae,Enterococcus,and Escherichia(P＜0.05),and lower abundance of Spirochaetes,Spirochaetaceae,Lachnospiraceae,Ruminococcaceae,Treponema,Prevotella,Coprococcus,Allobaculum,Ruminococcus,and Dorea(P＜0.05).The proximal colonic proteins Claudin1,Occludin,and ZO1 were significantly downregulated(P＜0.05).The open-field crossing frequency,sucrose preference index,and duration of tail suspension immobilization were improved in the five-element music group compared with those in the fear-stress group(P＜0.05),while DA and 5-HT levels were significantly restored in the hippocampus(P＜0.05),species diversity of the intestinal flora increased(P＜0.01)and changes in the abundance of the flora were reversed,and the proximal colonic proteins Occludin and ZO1 expression were significantly upregulated(P＜0.05).Conclusions Five-element music intervention during pregnancy can ameliorate fear-stress-induced depression behaviors and intestinal flora disorders in the offspring.