Objective To investigate the prognostic value of serum thrombospondin-1(THBS-1)combined with Alberta Stroke Program Early CT Score(ASPECTS)in patients with acute cerebral infarction with large vessel occlusion(ACI-LVO).Methods A total of 198 ACI-LVO patients admitted to the hospital from January 2022 to October 2024 were prospectively enrolled(ACI-LVO group).Patients were categorized into mild,moderate,and severe subgroups based on National Institutes of Health Stroke Scale(NIHSS)scores,and into good or poor prognosis groups based on 90-day outcomes.Serum THBS-1 levels were measured using ELISA,and ASPECTS scores were calculated.Spearman correlation analysis was used to assess the relationship between THBS-1,ASPECTS,and NIHSS scores.Prognostic factors and predictive values of THBS-1 and ASPECTS were also analyzed.Results Among the 198 patients,58 had mild,67 had moderate,and 73 had severe ACI-LVO.Serum THBS-1 levels increased,and ASPECTS scores decreased progressively with worsening disease severity(P<0.05).NIHSS scores were positively correlated with serum THBS-1 and negatively correlated with ASPECTS scores(P<0.05).The 90-day poor outcome rate was 37.37％(74/198).Independent risk factors for poor prognosis included older age,modified thrombolysis in cerebral infarction score of 0～2a,higher NIHSS score,larger infarct volume,hemorrhagic transformation,and elevated THBS-1.A higher ASPECTS score was an independent protective factor(P<0.05).The area under the curve(AUC)for predicting prognosis was 0.794 for THBS-1,0.831 for ASPECTS,and 0.903 for their combination,with the combined model showing superior predictive value(P<0.05).Conclusions Elevated serum THBS-1 and decreased ASPECTS scores are associated with increased disease severity and poorer prognosis in ACI-LVO patients.The combination of serum THBS-1 and ASPECTS score provides high predictive value for assessing prognosis in ACI-LVO patients.

Objective:To correlate the expression of interleukin-6 (IL-6), CD40 ligand (CD40L), and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) with regulatory T lymphocyte (Treg)/helper T lymphocyte 17 (Th17) in children with immune thrombocytopenic purpura (ITP) and to assess their combined diagnostic value.Methods:A retrospective study was conducted involving 80 children with ITP (ITP group) and 80 healthy children undergoing routine health screenings (control group) at Jinhua Central Hospital from February 2023 to February 2024. The levels of IL-6, CD40L, and sTREM-1, along with the Treg/Th17 ratio, were compared between the two groups and among children with different degrees of ITP severity. The correlations between IL-6, CD40L, and sTREM-1 and the severity of ITP, as well as the Treg/Th17 ratio were analyzed. Additionally, the diagnostic value of the combined tests was evaluated.Results:The levels of IL-6, CD40L, and sTREM-1 in the ITP group were (46.53 ± 8.69) ng/L, (6.51 ± 1.51), and (18.76 ± 3.72) ng/L, respectively. These values in the ITP group were significantly higher than those in the control group [(11.72 ± 1.58) ng/L, (4.31 ± 1.25), (8.07 ± 1.34) ng/L, t = 35.25, 10.04, 24.18, all P < 0.001]. The Treg/Th17 ratio in the ITP group was (1.34 ± 0.41), which was significantly lower than that in the control group [(13.56 ± 2.87), t = 37.70, P < 0.001]. In children with severe ITP, the levels of IL-6, CD40L, and sTREM-1 were (56.39 ± 11.70) ng/L, (9.62 ± 1.78), and (24.72 ± 4.81) ng/L, respectively. For those with moderate ITP, the levels were (45.41 ± 8.27) ng/L, (6.38 ± 1.40), and (17.69 ± 3.56) ng/L, respectively. In children with mild ITP, the levels were (37.04 ± 6.32) ng/L, (5.11 ± 1.32), and (14.50 ± 3.04) ng/L. The Treg/Th17 ratio in children with mild ITP was (0.95 ± 0.26), which was significantly lower than that in the moderate (1.37 ± 0.40) and severe (2.88 ± 0.56) groups. All differences were statistically significant among the three groups ( F = 23.98, 42.57, 37.15, 122.23, all P < 0.001). The levels of IL-6, CD40L, and sTREM-1 were positively correlated with the severity of ITP ( r = 0.565, 0.542, 0.538) and negatively correlated with the Treg/Th17 ratio ( r = -0.572, -0.536, -0.532), with all correlations being statistically significant (all P < 0.001). The receiver operating characteristic curve analysis indicated that the area under the curve values for the individual diagnoses of IL-6, CD40L, and sTREM-1 were 0.779, 0.750, and 0.763, respectively. In contrast, the area under the curve value for the combined diagnosis was 0.951, which was greater than that for each individual marker ( Z = 1.924, 2.137, 2.015, P = 0.037, 0.026, 0.031). Conclusions:The levels of IL-6, CD40L, and sTREM-1 in children with ITP are substantially correlated with the severity of ITP and the Treg/Th17 ratio, demonstrating notable diagnostic efficacy for ITP. Notably, the combination of IL-6, CD40L, and sTREM-1 greatly enhances diagnostic value.

Objective To investigate the prognostic value of serum thrombospondin-1(THBS-1)combined with Alberta Stroke Program Early CT Score(ASPECTS)in patients with acute cerebral infarction with large vessel occlusion(ACI-LVO).Methods A total of 198 ACI-LVO patients admitted to the hospital from January 2022 to October 2024 were prospectively enrolled(ACI-LVO group).Patients were categorized into mild,moderate,and severe subgroups based on National Institutes of Health Stroke Scale(NIHSS)scores,and into good or poor prognosis groups based on 90-day outcomes.Serum THBS-1 levels were measured using ELISA,and ASPECTS scores were calculated.Spearman correlation analysis was used to assess the relationship between THBS-1,ASPECTS,and NIHSS scores.Prognostic factors and predictive values of THBS-1 and ASPECTS were also analyzed.Results Among the 198 patients,58 had mild,67 had moderate,and 73 had severe ACI-LVO.Serum THBS-1 levels increased,and ASPECTS scores decreased progressively with worsening disease severity(P<0.05).NIHSS scores were positively correlated with serum THBS-1 and negatively correlated with ASPECTS scores(P<0.05).The 90-day poor outcome rate was 37.37％(74/198).Independent risk factors for poor prognosis included older age,modified thrombolysis in cerebral infarction score of 0～2a,higher NIHSS score,larger infarct volume,hemorrhagic transformation,and elevated THBS-1.A higher ASPECTS score was an independent protective factor(P<0.05).The area under the curve(AUC)for predicting prognosis was 0.794 for THBS-1,0.831 for ASPECTS,and 0.903 for their combination,with the combined model showing superior predictive value(P<0.05).Conclusions Elevated serum THBS-1 and decreased ASPECTS scores are associated with increased disease severity and poorer prognosis in ACI-LVO patients.The combination of serum THBS-1 and ASPECTS score provides high predictive value for assessing prognosis in ACI-LVO patients.

Objective:To correlate the expression of interleukin-6 (IL-6), CD40 ligand (CD40L), and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) with regulatory T lymphocyte (Treg)/helper T lymphocyte 17 (Th17) in children with immune thrombocytopenic purpura (ITP) and to assess their combined diagnostic value.Methods:A retrospective study was conducted involving 80 children with ITP (ITP group) and 80 healthy children undergoing routine health screenings (control group) at Jinhua Central Hospital from February 2023 to February 2024. The levels of IL-6, CD40L, and sTREM-1, along with the Treg/Th17 ratio, were compared between the two groups and among children with different degrees of ITP severity. The correlations between IL-6, CD40L, and sTREM-1 and the severity of ITP, as well as the Treg/Th17 ratio were analyzed. Additionally, the diagnostic value of the combined tests was evaluated.Results:The levels of IL-6, CD40L, and sTREM-1 in the ITP group were (46.53 ± 8.69) ng/L, (6.51 ± 1.51), and (18.76 ± 3.72) ng/L, respectively. These values in the ITP group were significantly higher than those in the control group [(11.72 ± 1.58) ng/L, (4.31 ± 1.25), (8.07 ± 1.34) ng/L, t = 35.25, 10.04, 24.18, all P < 0.001]. The Treg/Th17 ratio in the ITP group was (1.34 ± 0.41), which was significantly lower than that in the control group [(13.56 ± 2.87), t = 37.70, P < 0.001]. In children with severe ITP, the levels of IL-6, CD40L, and sTREM-1 were (56.39 ± 11.70) ng/L, (9.62 ± 1.78), and (24.72 ± 4.81) ng/L, respectively. For those with moderate ITP, the levels were (45.41 ± 8.27) ng/L, (6.38 ± 1.40), and (17.69 ± 3.56) ng/L, respectively. In children with mild ITP, the levels were (37.04 ± 6.32) ng/L, (5.11 ± 1.32), and (14.50 ± 3.04) ng/L. The Treg/Th17 ratio in children with mild ITP was (0.95 ± 0.26), which was significantly lower than that in the moderate (1.37 ± 0.40) and severe (2.88 ± 0.56) groups. All differences were statistically significant among the three groups ( F = 23.98, 42.57, 37.15, 122.23, all P < 0.001). The levels of IL-6, CD40L, and sTREM-1 were positively correlated with the severity of ITP ( r = 0.565, 0.542, 0.538) and negatively correlated with the Treg/Th17 ratio ( r = -0.572, -0.536, -0.532), with all correlations being statistically significant (all P < 0.001). The receiver operating characteristic curve analysis indicated that the area under the curve values for the individual diagnoses of IL-6, CD40L, and sTREM-1 were 0.779, 0.750, and 0.763, respectively. In contrast, the area under the curve value for the combined diagnosis was 0.951, which was greater than that for each individual marker ( Z = 1.924, 2.137, 2.015, P = 0.037, 0.026, 0.031). Conclusions:The levels of IL-6, CD40L, and sTREM-1 in children with ITP are substantially correlated with the severity of ITP and the Treg/Th17 ratio, demonstrating notable diagnostic efficacy for ITP. Notably, the combination of IL-6, CD40L, and sTREM-1 greatly enhances diagnostic value.

The clinical and genetic characteristics of the family reported with neurodevelopmental syndrome caused by the SPTBN1 gene mutation were analyzed for clinical diagnosis.The proband was a boy, 2 years and 3 months old, admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in June 2022 with comprehensive developmental delays as the main manifestation.The boy was backward in development since childhood.He was able to raise his head at the age of 3 months and sit alone at the age of 11 months.He could stand up with support but was unable to climb.He occasionally spoke polysyllabic words.The proband′s elder brother, 3 years and 1 month old, was able to walk at the age of 1 year and 6 months, and could speak " Mom and Dad" consciously and understand some instructions.He liked to play with other children.The mother of the proband was mentally retarded, while the father and grandparents of the proband had no symptoms.The proband was found to have a heterozygous mutation of the SPTBN1 gene (NM_003128.3), c.811G>A (p.Val271Met).The proband′s mother and elder brother also had a heterozygous mutation, which, however, was not detected in the proband′s father.The neurodevelopmental syndrome caused by the SPTBN1 gene mutation is rare in China, which can be manifested as language and motor delays and intellectual disabilities from early childhood, and individuals with the same genetic variation show different clinical phenotypes.

Objective:To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age.Methods:Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis. The analysis included variant carrier rate, gene carrier rate, cumulative carrier rate, at-risk couple rates, and variant spectrum.Results:(1) Pathogenic variants were identified in 1 472 (47.53%, 1 472/3 097) individuals, with an average of 0.65 pathogenic variants per individual. The rate of at-risk couples was 3.93% (56/1 424). (2) A total of 180 genes were identified, with 16 genes exhibiting a gene carrier rate of ≥1% and 33 genes having a rate of ≥0.5%, most of which were associated with inherited metabolic diseases. Noteworthy genes with higher gene carrier rates and high-frequency variants included GJB2: c.235del, PAH: c.728G>A, ATP7B: c.2333G>T, SLC26A4: c.919-2A>G, GALC: c.1901T>C, POLG: c.2890C>T, SLC22A5: c.1472C>G, USH2A: c.2802T>G, SLC25A13: c.852_855del, GAA: c.761C>T and c.752C>T. Conclusion:This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population, laying a foundation for the development of ECS programs tailored to the Chinese population.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

OBJECTIVE To investigate possible electrophysiological mechanisms of psychogenic disorders caused by the classical hallucinogen 2,5-dimethoxy-4-methylamphetamine(DOM).METHODS Microelectrode array implantation in the orbitofrontal cortex(OFC)was performed in adult male SD rats.After one week of recovery from surgery,the drugs were administered intraperitoneally to rats in the following order:DOM(0.5,1.5,and 3.0 mg·kg-1),DOM 3.0 mg·kg-1+ketanserin 1.0 mg·kg-1,DOM 3.0 mg·kg-1+SB242084 3.0 mg·kg-1,ketanserin 1.0 mg·kg-1,SB242084 3.0 mg·kg-1.Saline was given as a control group before each drug treatment.The changes of field potential(LFP)in OFC were recorded by the Plexon in vivo multichannel recording system.There was one week of washout of drugs between medications.RESULTS DOM(0.5,1.5 and 3.0 mg·kg-1)increased the power of high frequency oscillations(HFO,P<0.05)but decreased the power of low γ oscillations(P<0.05,P<0.01)in OFC compared to saline.Ketanserin(1.0 mg·kg-1)antagonized DOM induced changes in low γ oscilla-tions(P<0.01)and HFO(P<0.05)power,but SB242084(3.0 mg·kg-1)did not.CONCLUSION DOM can cause such psychoneurological disorders as hallucinations,which may be related to the power decrease of low γ oscillations and increase of HFO in OFC by acting at 5-HT2A receptors.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.