This study identified CLDN14 gene variants in two Chinese Han pedigrees with autosomal recessive deafness 29 through whole-exome sequencing. The proband in pedigree 1 carried the known pathogenic variant c.301G>A (p.Gly101Arg) and a novel variant c.370delC (p.Leu124Serfs*33), classified as pathogenic according to the American College of Medical Genetics and Genomics standards (PVS1+PS2+PM2). The proband in pedigree 2 carried two novel variants, c.51dupC (p.Met18Hisfs*142) and c.74_76delCCA (p.Thr25del), both classified as likely pathogenic. Short tandem repeat analysis confirmed the familial relationship in pedigree 1. Prenatal diagnosis revealed that the fetuses in both pedigrees had inherited only a single heterozygous variant. Postnatal hearing screening in pedigree 1 and a 3-year follow-up in pedigree 2 revealed no abnormalities.

Ischemic stroke(IS),caused by the interruption of cerebral blood flow,results in localized ischemia and hypoxia in the brain tissue.Its pathophysiological mechanisms are complex,involving disturbances in energy metabo-lism,oxidative stress,inflammation,and apoptosis.As the cell's powerhouse,mitochondria play a critical role in IS,and their dysfunction exacerbates neuronal injury.In recent years,tunneling nanotubes(TNTs),a novel form of intercellular communication,have gained increasing attention for their role in mediating the intercellular transfer of functional mito-chondria.Studies have shown that both stem cells and astrocytes can transfer healthy mitochondria to damaged neurons via TNTs,thereby restoring energy metabolism,reducing apoptosis,and alleviating neurological deficits.This review summa-rizes the current research on the mechanisms and biological functions of TNT-mediated mitochondrial transfer and discuss-es its potential therapeutic applications in IS,aiming to provide insight into IS treatment strategies.

Objective: To analyze the regulatory effect of Atractylodes macrocephala Koidz. extract on the immune function of mice, so as to provide a reference for the study of the mechanism of Atractylodes macrocephala Koidz. regulating immune function. Methods: Forty-eight SPF healthy male ICR mice were randomly divided into control group and low (0.5 g/kg), medium (2.0 g/kg), and high (4.0 g/kg) dose groups, with 12 mice in each group. The mice in control group were given the pure water by gavage once a day, while the mice in each dose group were given the corresponding dose of Atractylodes macrocephala Koidz. extract by gavage once a day. The delayed allergy test was performed for 28 consecutive days. Sixty SPF healthy male ICR mice were randomly divided into a control group, polyinosinic acid injection group (model group), and low, medium, and high dose groups, with 12 mice in each group. The mice in control group were given the pure water by gavage once a day, while the mice in each dose group were given the corresponding dose of Atractylodes macrocephala Koidz. extract by gavage once a day for 14 consecutive days. On days 13 and 14 of administration, the mice in the model group and each dose group were intraperitoneally injected with sterile polyinosinic acid solution to perform the immunosuppressive experiment induced by polyinosinic acid. The mouse ear pieces were weighed, and the thymus and spleen of the mice were weighed and stained with HE to calculate the pathological scores. Peripheral blood was collected for blood cell detection and T cell classification. Results: Mice in each group had normal feeding, activity, and growth status, and no abnormality was observed. In the delayed allergy test, compared with the control group, the degree and rate of ear swelling in the low, medium and high dose groups were higher, the white blood cell count in the medium dose group was higher, and the absolute values of lymphocytes in the low and medium dose groups were higher (all P<0.05). Compared with the control group, the pathological scores of the thymus and spleen in the model group were higher (both P<0.05). In the immunosuppressive experiments in mice induced by polyinosinic acid, compared with the model group, the pathological score of the thymus in the high dose group was lower (P<0.05), and the boundary between the thymus cortex and medulla was improved. Conclusions Atractylodes macrocephala Koidz. extract can increase the degree of ear swelling and peripheral blood white blood cell count in mice. High dose of Atractylodes macrocephala Koidz. extract can improve the thymus injury induced by polyinosinic acid, and has an immunomodulatory effect.

Serving as cerebral macrophages， microglial cells are meticulously regulated by the microenvironment of the central nervous system.In response to various environmental and cellular stresses， microglial cells are rapidly activated and exhibit either pro-inflammatory or anti-inflammatory phenotypes to maintain brain tissue homeostasis， and during this process， significant changes are observed in glucose metabolism of microglial cells. Aerobic glycolysis is the primary energy source for pro-inflammatory microglial cells， while oxidative phosphorylation is the energy source for anti-inflammatory microglial cells.This article systematically elaborates on glucose metabolism and glucose metabolic reprogramming pathways in microglial cells， as well as their role in central nervous system diseases. In addition， this article also discusses the potential of targeting glucose metabolic reprogramming in microglial cells for the treatment of related diseases.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.

Objective:To explore the guiding significance of Expanded Carrier Screening (ECS) for the fertility process of individuals undergoing Assisted Reproductive Technology (ART) in Dalian.Methods:A retrospective analysis was conducted on the ECS results of patients who visited the Dalian Maternal and Child Health Care Center (Group) from January 2023 to June 2024. The study included the screening of 155 monogenic diseases and the ART status of carrier couples.Results:Among the 1 384 patient samples, 490 carriers were identified, yielding a detection rate of 35.41% (490/1 384). A total of 100 diseases and 91 pathogenic genes were detected. The most frequently identified disease was autosomal recessive hearing loss type 4 (SLC26A4), with a carrier rate of 3.54% (49/1384). For the 490 carriers, their partners were recalled for testing and, 322 partners participated. Eight high-risk couples were identified, accounting for 2.48% (8/322). Among the 322 couples, 4 used artificial insemination by husband (AIH, 1.24%, 4/322), 166 used in vitro fertilization (IVF, 51.55%, 166/322), 139 used intracytoplasmic sperm injection (ICSI, 43.17%, 139/322), and 1 underwent preimplantation genetic testing for monogenic diseases (PGT-M, 0.31%, 1/322). Twelve couples (3.73%, 12/322) did not undergo ART, were not pregnant, or chose gamete donation. Among the eight high-risk couples, three underwent IVF, four underwent ICSI, and one underwent PGT-M. One couple conceived through ICSI, and the fetus was followed up. Amniotic fluid Sanger sequencing revealed that the fetus had compound heterozygous mutations in the PAH gene, with two suspected pathogenic variants at c.532G>A and c.1174T>A. One couple undergoing PGT-M currently has one retrieved oocyte and zero usable blastocysts. The embryo carries a paternal mutation and is aneuploid.Conclusions:This study not only identified the common pathogenic diseases in Dalian, providing a reference for clinical treatment, but also validated the critical significance of ECS for individuals undergoing ART.

Ischemic stroke(IS),caused by the interruption of cerebral blood flow,results in localized ischemia and hypoxia in the brain tissue.Its pathophysiological mechanisms are complex,involving disturbances in energy metabo-lism,oxidative stress,inflammation,and apoptosis.As the cell's powerhouse,mitochondria play a critical role in IS,and their dysfunction exacerbates neuronal injury.In recent years,tunneling nanotubes(TNTs),a novel form of intercellular communication,have gained increasing attention for their role in mediating the intercellular transfer of functional mito-chondria.Studies have shown that both stem cells and astrocytes can transfer healthy mitochondria to damaged neurons via TNTs,thereby restoring energy metabolism,reducing apoptosis,and alleviating neurological deficits.This review summa-rizes the current research on the mechanisms and biological functions of TNT-mediated mitochondrial transfer and discuss-es its potential therapeutic applications in IS,aiming to provide insight into IS treatment strategies.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective:To explore the guiding significance of Expanded Carrier Screening (ECS) for the fertility process of individuals undergoing Assisted Reproductive Technology (ART) in Dalian.Methods:A retrospective analysis was conducted on the ECS results of patients who visited the Dalian Maternal and Child Health Care Center (Group) from January 2023 to June 2024. The study included the screening of 155 monogenic diseases and the ART status of carrier couples.Results:Among the 1 384 patient samples, 490 carriers were identified, yielding a detection rate of 35.41% (490/1 384). A total of 100 diseases and 91 pathogenic genes were detected. The most frequently identified disease was autosomal recessive hearing loss type 4 (SLC26A4), with a carrier rate of 3.54% (49/1384). For the 490 carriers, their partners were recalled for testing and, 322 partners participated. Eight high-risk couples were identified, accounting for 2.48% (8/322). Among the 322 couples, 4 used artificial insemination by husband (AIH, 1.24%, 4/322), 166 used in vitro fertilization (IVF, 51.55%, 166/322), 139 used intracytoplasmic sperm injection (ICSI, 43.17%, 139/322), and 1 underwent preimplantation genetic testing for monogenic diseases (PGT-M, 0.31%, 1/322). Twelve couples (3.73%, 12/322) did not undergo ART, were not pregnant, or chose gamete donation. Among the eight high-risk couples, three underwent IVF, four underwent ICSI, and one underwent PGT-M. One couple conceived through ICSI, and the fetus was followed up. Amniotic fluid Sanger sequencing revealed that the fetus had compound heterozygous mutations in the PAH gene, with two suspected pathogenic variants at c.532G>A and c.1174T>A. One couple undergoing PGT-M currently has one retrieved oocyte and zero usable blastocysts. The embryo carries a paternal mutation and is aneuploid.Conclusions:This study not only identified the common pathogenic diseases in Dalian, providing a reference for clinical treatment, but also validated the critical significance of ECS for individuals undergoing ART.