Objective To explore the protective effect and related mechanism of Compound Baimai Powder(CBMP,a compound description of Mongolian medicine)on astrocytes after oxygen glu-cose deprivation and reoxygenation(OGD/R)injury.Methods Astrocyte model of OGD/R injury was subjected to simulate in vitro cerebral ischemia/reperfusion injury.Cultured astrocytes were randomly divided into normal group,OGD/R group,OGD/R+nimodipine group(10 μmol/L),OGD/R+low-and high-dose CBMP groups(25,50 μmol/L).Cell viability and apoptosis were de-tected with CCK-8 assay and flow cytometry,respectively.Western blotting was used to measure the expression levels of the proteins related to the nuclear factor erythroid-2-related factor-2(NRF2)/antioxidant response element and Janus kinase(J AK)/signal transducer and activator of transcription(STAT)signaling pathways.ELISA was employed to examine the levels of inflam-matory factors IL-1β,IL-6,and TNF-α,as well as oxidative stress molecules ROS,GSH,MDA and SOD.Results Compared to the normal group,the OGD/R group showed significant decreases in cell viability,NRF2 protein level,and SOD and GSH activities(P＜0.05,P＜0.01),and obvious increases in p-JAK and p-STAT proteins levels,contents of IL-1β,IL-6 and TNF-α,and ROS and MDA levels(P＜0.05,P＜0.01).High-dose CBMP treatment resulted in notably elevated cell via-bility and NRF2 protein level,while reduced levels of p-JAK[(1.20±0.20)vs(2.50±0.26)]and p-STAT[(1.15±0.25)vs(2.10±0.21)]proteins,IL-6[(30.33±5.20)vs(180.35±18.50)]and TNF-α[(50.12±8.24)vs(160.45±15.20)]when compared to the OGD/R group(P＜0.05,P＜0.01).Conclusion CBMP exerts protective effect on astrocytes against OGD/R injury.

Objective:To analyze the clinical characteristics of anti-melanoma differentiation associated gene 5 (MDA5) antibody-positive juvenile dermatomyositis (JDM) patients.Methods:A retrospective case-control study was conducted. The positive group included 18 children with anti-MDA5 antibody-positive JDM who were admitted to the Department of Rheumatology and Immunology at Capital Center for Children′s Health with Capital Medical University between January 2016 and January 2023. Another 36 children with anti-MDA5 antibody-negative JDM hospitalized during the same period were enrolled as the negative group. Based on the extent of pulmonary involvement and pulmonary CT scores, the MDA5-positive group was further divided into severe pulmonary involvement and non-severe pulmonary involvement subgroups. Chi-square test and Kruskal-Wallis test were used to compare clinical features, laboratory test results between groups.Results:Among the 18 patients in the MDA5-positive group, 7 were male and 11 were female, with an age of onset of 5.0 (2.6, 9.4) years and disease duration of 6.0 (4.0, 9.3) months. The MDA5-negative group included 36 cases (14 male, 22 female), with an age of onset of 4.9 (2.0, 7.0) years and disease duration of 5.0 (1.8, 7.0) months. The MDA5-positive group exhibited significantly higher rates of arthritis, skin ulcers, and interstitial lung disease (ILD), along with elevated serum ferritin (SF) and erythrocyte sedimentation rate levels compared to the MDA5-negative group (9/18 vs. 11% (4/36), 6/18 vs. 3% (1/36), 16/18 vs. 33% (12/36), 327 (141, 518) vs. 131 (68, 257) μg/L, 17.5 (12.5, 26.8) vs. 11.0 (5.0, 13.0) mm/1 h, χ2=7.92, 7.41, 14.84, Z=2.50, 2.87, all P<0.05). Conversely, the MDA5-positive group had lower rates of muscle weakness and lower creatine kinase levels (5/18 vs. 75% (27/36), 58.5 (49.3, 97.5) vs. 225.0 (68.0, 695.5) U/L, χ2=11.08, Z=-2.94, both P<0.05). Severe pulmonary involvement 6 cases and non-severe pulmonary involvement subgroups 12 cases. Among the MDA5-positive patients, those in the severe pulmonary involvement subgroup had an older age at onset and higher rates of muscle weakness as well as hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), SF, and Krebs von den Lungen-6 (KL-6) compared to the non-severe subgroup (all P<0.05). In the MDA5-positive group, 17 patients improved after treatment with glucocorticoids combined with immunosuppressants, while One died due to rapidly progressive ILD. Conclusions:Anti-MDA5 antibody-positive JDM is characterized by typical skin rashes, a high incidence of arthritis and skin ulcers, relatively mild muscle involvement, but is prone to ILD. Among MDA5-positive patients, those with older age at onset, muscle involvement (manifested as muscle weakness and elevated muscle enzymes (LDH, HBDH)), or significantly elevated KL-6 and SF levels are more likely to develop severe pulmonary complications.

Objective:To analyze the clinical characteristics of mannose phosphate isomerase-congenital disorders of glycosylation (MPI-CDG) and evaluated the outcomes following D-mannose treatment.Methods:This case-series study analyzed clinical manifestations, laboratory findings, imaging results, genetic data, and outcomes after D-mannose therapy in 5 children with MPI-CDG diagnosed at the Children′s Hospital of Fudan University between December 2014 and December 2024.Results:The age of onset ranged from 0.3 to 0.4 years in all 5 children, who initially presented with diarrhea and hypoglycemia. Associated manifestations included short stature (3 cases), anemia (3 cases), splenomegaly (3 cases), hepatomegaly (4 cases), elevated transaminases (4 cases), and hypoalbuminemia (4 cases). Liver pathology revealed hepatic fibrosis in 3 cases. Genetic testing identified 8 variants in the MPI gene, including 2 novel variants. Following D-mannose treatment, diarrhea and hypoglycemia resolved within 1-2 weeks in all children, with concurrent improvement in anemia. Notably except for Patient 1, who developed progressive splenomegaly, worsening hepatic fibrosis, and portal hypertension despite persistently normal transaminase and albumin levels, the other 4 children showed improvement in transaminase levels, resolution of hypoalbuminemia and amelioration of imaging abnormalities.Conclusions:MPI-CDG typically manifests in infancy with diarrhea and hypoglycemia, often accompanied by multi-system involvement. D-mannose treatment significantly improves metabolic abnormalities and most organ damages. However, close surveillance of liver status is warranted due to the risk of hepatic fibrosis progression in some cases.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.

Objective: To evaluate the clinical efficacy of costal cartilage septal-columellar composite grafts in refining nasal tip aesthetics for secondary unilateral cleft lip nasal deformities, and to provide a reference for clinical treatment. Methods: This study has been approved by the institutional medical ethics committee and informed consent was obtained from the patients. A total of 31 patients underwent surgery with a costal cartilage strut-septum complex stent graft. The follow-up period was a minimum of 6 months. Anteroposterior, lateral, and supine photos of the patient were taken before and after the operation. The following measurements were obtained: nasal tip projection (NTP), nasofrontal angle (NFA), nasolabial angle (NLA), nasal tip alar angle (NAA), and nasal tip tangent angle (NTA). Nostril-related indices [nostril area (S), nostril height (h1), nostril width (w), and nasal sill height (h2)]) were measured before and after surgery, and cleft/non-cleft side ratios were calculated. Satisfaction with nasal tip aesthetics was investigated using the visual analogue scale (VAS). All measurements were made using preoperative photographs and the most recent follow-up photographs of the patients. Results The follow-up period ranged from 6 to 49 months, with an average of 28 months. All patients underwent healing Results: The follow-up period ranged from 6 to 49 months, with an average of 28 months. All patients underwent healing by first intention. Compared with preoperative measurements, postoperative NTP (preoperative 0.48 vs. postoperative 0.55), NLA (preoperative 83.98° vs. postoperative 100.80°), and NAA (preoperative 160.30° vs. postoperative 168.40°) were significantly increased (P < 0.05). NFA (preoperative 139.20° vs. postoperative 133.50°, P < 0.05) and NTA (preoperative 43.76° vs. postoperative 35.80°, P = 0.062) were decreased. On the cleft versus non-cleft sides, the ratios of S (preoperative 1.10 vs. postoperative 0.94, P < 0.05), w (preoperative 1.10 vs. postoperative 1.02, P = 0.194), h1 (preoperative 0.71 vs. postoperative 0.90, P < 0.05), and h2 (preoperative 0.53 vs. postoperative 0.79, P = 0.065) were all near 1. Satisfaction with postoperative results was fairly high. Conclusion The costal cartilage strut-septum complex stent can effectively correct the deflection and collapse of the nasal tip in patients with unilateral cleft lip nose deformity. The postoperative long-term effect is relatively stable.

PURPOSE: To investigate the regulatory role of nerve injury-induced protein 1 (NINJ1) in the anti-inflammatory function of human umbilical cord mesenchymal stem cells (hUC-MSCs) co-stimulated by interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). METHODS: hUC-MSCs were expanded in vitro using standard protocols, with stem cell characteristics confirmed by flow cytometry and multilineage differentiation assays. The immunomodulatory properties and cellular activity of cytokine-co-pretreated hUC-MSCs were systematically evaluated via quantitative reverse transcription RT-qPCR, lymphocyte proliferation suppression assays, and Cell Counting Kit-8 viability tests. Transcriptome sequencing, Western blotting and small interfering RNA interference were integrated to analyze the regulatory mechanisms of NINJ1 expression. Functional roles of NINJ1 in pretreated hUC-MSCs were elucidated through gene silencing combined with lactate dehydrogenase release assays, Annexin V/Propidium Iodide apoptosis analysis, macrophage co-culture models, and cytokine Enzyme-Linked Immunosorbent Assay. Therapeutic efficacy was validated in a cecal ligation and puncture-induced septic mouse model: 80 mice were randomly allocated into 4 experimental groups (n=20/group): sham group (laparotomy without cecal ligation); phosphate-buffered saline-treated group (cecal ligation and puncture (CLP) + 0.1 mL phosphate-buffered saline); hUC-MSCs (small interfering RNA (siRNA)-interferon-gamma and tumor necrosis factor-alpha co-stimulation (IT))-treated group (CLP + hUC-MSCs transfected with scrambled siRNA); and hUC-MSCs (siNINJ1-IT)-treated group (CLP + hUC-MSCs with NINJ1-targeting siRNA). RESULTS: hUC-MSCs demonstrated compliance with International Society for Cellular Therapy criteria, confirming their stem cell identity. IFN-γ/TNF-α co-pretreatment enhanced the immunosuppressive capacity of hUC-MSCs, accompanied by the reduction of cellular viability, while concurrently upregulating pro-inflammatory cytokines such as interleukin-6 and interleukin-1β. This co-stimulation significantly elevated NINJ1 expression in hUC-MSCs, whereas genetic silencing of NINJ1 effectively suppressed pro-inflammatory cytokine production and attenuated damage-associated molecular patterns release through inhibition of programmed plasma membrane rupture. Furthermore, the NINJ1 interference potentiated the ability of cytokine-pretreated hUC-MSCs to suppress LPS-induced pro-inflammatory responses in RAW264.7 macrophages. In cecal ligation and puncture-induced sepsis model, NINJ1-silenced hUC-MSCs exhibited enhanced therapeutic efficacy, manifested by reduced systemic inflammation and multi-organ damage. CONCLUSION Our findings shed new light on the immunomodulatory functions of cytokine-primed MSCs, offering groundbreaking insights for developing MSC-based therapies against inflammatory diseases via interfering the expression of NINJ1.
Mesenchymal Stem Cells/drug effects* ; Animals ; Interferon-gamma/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Humans ; Mice ; Umbilical Cord/cytology* ; Cells, Cultured ; Apoptosis ; Male

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder, with symptoms of menstrual disorders, hirsutisms, acne, and obesity. Studies have found that PCOS patients have a higher prevalence of anxiety, depression and sleep disorders than non-PCOS women, which may be related to the abnormal innervation. Meanwhile, it has been found that PCOS patients exhibit lower central level and higher peripheral levels of monoamine neurotransmitters (5-hydroxytryptamine, dopamine and norepinephrine). These imbalances can affect various clinical manifestations of PCOS, including the formation and development of metabolic and reproductive disorders, as well as anxiety and sleep disorders, through multiple pathways. This review summarizes recent research progress on the role of monoamine neurotransmitters in the physiological characteristics and clinical manifestations of PCOS patients, aiming to provide new insights into the neuroendocrine characteristics and pathogenesis of the syndrome.

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder, with symptoms of menstrual disorders, hirsutisms, acne, and obesity. Studies have found that PCOS patients have a higher prevalence of anxiety, depression and sleep disorders than non-PCOS women, which may be related to the abnormal innervation. Meanwhile, it has been found that PCOS patients exhibit lower central level and higher peripheral levels of monoamine neurotransmitters (5-hydroxytryptamine, dopamine and norepinephrine). These imbalances can affect various clinical manifestations of PCOS, including the formation and development of metabolic and reproductive disorders, as well as anxiety and sleep disorders, through multiple pathways. This review summarizes recent research progress on the role of monoamine neurotransmitters in the physiological characteristics and clinical manifestations of PCOS patients, aiming to provide new insights into the neuroendocrine characteristics and pathogenesis of the syndrome.

Objective:To study the effects of epidermal growth factor(EGF)on the coordinated motor behaviors and changes of nigrostriatal dopaminergic system under the impact of EGF in middle-aged rats.Methods:Healthy aged Sprague Dawley(SD)rats were subcutaneously administered EGF(0.1 mg/ml)in the dorsal region for 7 days.Adhe-sive removal test,tapered beam walking test and descending a wire mesh pole test were performed to detect the changes in the coordinated motor behaviors of rats as well as changes in the expression of tyrosine hydroxylase(TH)and dopa-mine transporter(DAT)of nigrostriatal dopaminergic system in rats.Results:Middle-aged rats showed reduced behav-ioral parameters of adhesive removal test,tapered beam walking test and descending a wire mesh pole test compared with those of adult rats(P<0.05),which were improved after treatment with EGF(P<0.05).The expression of TH and DAT in nigrostriatal dopaminergic system was down-regulated in middle-aged rats compared with that in adult rats(P<0.01),however,which were up-regulated after treatment with EGF(P<0.01).Conclusion:EGF can amelio-rate the decline in coordinated motor behaviors and increases the activity of nigrostriatal dopaminergic system in middle-aged rats.

Objective:To study the effects of epidermal growth factor(EGF)on the coordinated motor behaviors and changes of nigrostriatal dopaminergic system under the impact of EGF in middle-aged rats.Methods:Healthy aged Sprague Dawley(SD)rats were subcutaneously administered EGF(0.1 mg/ml)in the dorsal region for 7 days.Adhe-sive removal test,tapered beam walking test and descending a wire mesh pole test were performed to detect the changes in the coordinated motor behaviors of rats as well as changes in the expression of tyrosine hydroxylase(TH)and dopa-mine transporter(DAT)of nigrostriatal dopaminergic system in rats.Results:Middle-aged rats showed reduced behav-ioral parameters of adhesive removal test,tapered beam walking test and descending a wire mesh pole test compared with those of adult rats(P<0.05),which were improved after treatment with EGF(P<0.05).The expression of TH and DAT in nigrostriatal dopaminergic system was down-regulated in middle-aged rats compared with that in adult rats(P<0.01),however,which were up-regulated after treatment with EGF(P<0.01).Conclusion:EGF can amelio-rate the decline in coordinated motor behaviors and increases the activity of nigrostriatal dopaminergic system in middle-aged rats.