Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice.Methods Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases,which were subjected to GO and KEGG analysis,and the binding energy was verified using molecular docking.In a mouse model of cecal ligation and puncture(CLP),the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining.Serum levels of CK-MB,LDH,MDA,IL-1β and IL-18 and myocardial ROS level in the mice were detected,and Western blotting was used to determine the protein expression levels of STAT3,GSDMD,caspase-11,JAK2,P-STAT3,P-JAK2,GSDMD-N and HMGB1 in the myocardial tissues.Results Five core targets were screened from the 10 intersecting genes.Molecular docking showed strong binding affinity of plumbagin to STAT3,p-STAT3,and JAK2.Compared with the sham-operated mice,the mouse models of CLP-induced sepsis had significantly decreased CO,LVEF,LVFS and SV and increased serum levels of CK-MB,LDH,MDA and myocardial inflammatory factors and ROS.HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins(P<0.05).Pretreatment with plumbagin significantly improved cardiac functions of CLP mice,lowered serum levels of CK-MB,LDH,MDA,inflammatory factors and myocardial ROS,and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins.Conclusion Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Objective To investigate whether resveratrol alleviates hyperglycemia-induced cardiomyocyte hypertrophy by enhancing the expression of silent information regulation 2 homolog 1(SIRT1)to maintain mitochondrial homeostasis.Methods Rat cardiomyocytes H9c2 cells with or without lentivirus-mediated mRNA interference of SIRT1 were cultured in high glucose(HG)and treated with resveratrol for 72 h.The changes in superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,reactive oxygen species(ROS)level,and relative surface of the cells were examined,and the mRNA expressions of atrial natriuretic factor(ANF)and brain natriuretic peptide(BNP)and protein expressions of SIRT1,mitochondrial fusion related proteins optic atrophy protein 1(OPA1)and mitofusin 2,mitochondrial division related proteins dynamin-related protein 1(DRP1)and fission protein 1(FIS1),and mitophagy-related proteins BNIP3L and LC3 were detected using RT-qPCR and Western blotting.Results HG exposure significantly decreased SOD activity,increased MDA content,ROS production,relative cell surface,and the mRNA expressions of ANF and BNP in the cardiomyocytes;the protein expressions of SIRT1,OPA1,mitofusin 2 and BNIP3L and LC3-Ⅱ/LC3-Ⅰ ratio were all decreased and the protein expressions of DRP1 and FIS1 increased in HG-exposed cells(P<0.01).All these changes in HG-exposed cardiomyocytes were significantly alleviated by treatment with resveratrol(P<0.05).The protective effects of resveratrol against HG exposure in the cardiomyocytes were obviously attenuated by transfection of the cells with si-SIRT1(P<0.05).Conclusion Resveratrol inhibits hyperglycemia-induced cardiomyocyte hypertrophy by reducing oxidative stress,the mechanisms of which involve enhancement of SIRT1 protein expression,regulation of mitochondrial fusion and division balance,and promoting BNIP3L-mediated mitophagy to maintain mitochondrial homeostasis in the cells.

Objective:To investigate the expression of c-Src in cholangiocarcinoma (CCA) and its relationship with clinical pathological features.Methods:The bile duct tissue of 68 CCA patients who underwent surgical resection at the Lhasa People′s Hospital from January 2017 to December 2022 and the normal bile duct tissue of 18 patients with common bile duct stones were selected. The expression of c-Src in bile duct tissue was detected using SP immunohistochemistry, and the expression of c-Src in CCA and its relationship with clinical pathological features were analyzed.Results:The positive rate of c-Src in CCA tissue was 58.82%(40/68), significantly higher than the 16.67%(3/18, P<0.01) in normal bile duct tissue. The expression score of c-Src in CCA tissues with metastasis was significantly higher than that in CCA tissues without metastasis ( P<0.01). Conclusions:The expression of c-Src is significantly increased in CCA tissues, and the expression of c-Src is also significantly increased in CCA tissues with metastasis, indicating that c-Src promotes the invasion and metastasis of CCA.

The incidence rate of anxiety and depression is significantly higher in patients with inflammatory bowel diseases (IBD) than in the general population. The mechanisms underlying dextran sulfate sodium (DSS)-induced depressive-like behaviors are still unclear. We clarified that IBD mice induced by repeated administration of DSS presented depressive-like behaviors. The paraventricular thalamic nucleus (PVT) was regarded as the activated brain region by the number of c-fos-labeled neurons. RNA-sequencing analysis showed that lipocalin 2 (Lcn2) was upregulated in the PVT of mice with DSS-induced depressive behaviors. Upregulating Lcn2 from neuronal activity induced dendritic spine loss and the secreted protein induced chemokine expression and subsequently contributed to microglial activation leading to blood-brain barrier permeability. Moreover, Lcn2 silencing in the PVT alleviated the DSS-induced depressive-like behaviors. The present study demonstrated that elevated Lcn2 in the PVT is a critical factor for DSS-induced depressive behaviors.
Mice ; Humans ; Animals ; Lipocalin-2/genetics* ; Midline Thalamic Nuclei ; Brain ; Inflammatory Bowel Diseases ; Proto-Oncogene Proteins c-fos ; Mice, Inbred C57BL

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

【Objective】 To compare the supply data of red blood cells(RBCs) from 18 blood centers in China before and after the outbreak of COVID-19 during 2018 to 2021. 【Methods】 Eight indicators related to RBCs supply from 18 blood centers in China during 2018-2021 were collected retrospectively, including the storage of total amount of qualified RBCs (referred to as the total amount of storage), the distribution of total amount of RBCs (referred to as the total amount of distribution), the distribution amount of RBCs per 1 000 population (referred to as the amount of distribution per 1 000 population), the distribution amount of RBCs from 400 mL original blood per 1 000 population [referred to as the amount of distribution per 1 000 population (400 mL)], the average daily distribution amount of RBCs (referred to as the average daily distribution amount), the average daily storage amount of RBCs (referred to as the average daily storage amount), the average storage days of RBCs when distribute (referred to as the RBC storage days), and the expired amount of RBCs (referred to as the expired amount). Based on the outbreak time of COVID-19, the data of 2018 and 2019 were the pre-pandemic group, and the data of 2020 and 2021 were the post-pandemic group. 【Results】 Data on RBCs supply in 18 blood centers from 2018 to 2021(comparison of the pre-pandemic group and the post-pandemic group): the amount of distribution per 1 000 population (median 14.68 U>13.92 U) decreased, the amount of distribution per 1 000 population (400 mL) (median 10.16 U>9.21 U) decreased, and the difference was statistically significant (P<0.05); data comparison between 2019 and 2020:the total amount of distribution (median 117 770.38 U>99 084.08 U) decreased, the amount of distribution per 1 000 population (median 15.04 U>12.19 U) decreased, the amount of distribution per 1000 population (400 mL) (median 10.11 U>8.94 U), the average daily distribution amount(322.66 U>270.73 U) decreased and RBC storage days (median 10.50 d<11.45 d) increased, the difference has statistical significance (P<0.05); data comparison between 2020 and 2021:the total amount of storage (median 101 920.25 U<120 328.63 U), the total amount of distribution (median 99 084.08 U<118 428.62 U), the amount of distribution per 1 000 population (median 12.19 U<15.00 U), the amount of distribution per 1 000 population (400 mL) (median 8.94 U<9.46 U), the average daily distribution amount (270.73 U>324.46 U), the average daily inventory (median 3 222.00 U<4 328.00 U) increased, the expired amount (median 1.50 U>0.00 U) decreased, the difference has statistical significance (P<0.05). The results of ANOVA showed that there were significant differences on the data related to RBCs supply (except expired amount) in different blood centers (P<0.05). The ratio of average daily stock to average daily distribution in the post-outbreak group (median 12.36 d) was higher than that in the pre-outbreak group (median 10.92 d), the difference has statistical significance (P<0.05), with significant difference among different blood centers (P <0.05). 【Conclusion】 The COVID-19 pandemic has a significant impact on RBCs supply in different blood centers. In the second year of the pandemic, the supply capability had recovered to some extent, and there were differences in RBCs supply in different blood centers.

OBJECTIVE: To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis. METHODS: Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe³⁺ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue. RESULTS: Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (μmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group. CONCLUSIONS Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.
Mice ; Male ; Animals ; Aldehyde Dehydrogenase, Mitochondrial ; Ferroptosis ; Reactive Oxygen Species ; Chemical and Drug Induced Liver Injury, Chronic ; Dimethyl Sulfoxide ; Mice, Inbred C57BL ; Sepsis ; Disease Models, Animal