Objective To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule(XFC)on interleukin(IL)-1β-induced impairment of chondrocytes.Methods XFC-medicated serum was collected from SD rats with XFC gavage,and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry.Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2.In cultured human chondrocytes induced with IL-1β,the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum,alone or in combination,on expression levels of IL-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 were examined with ELISA,and the changes in the expressions of collagen type Ⅱ alpha 1(COL2A1),matrix metalloproteinase 13(MMP13),adisintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR,Western blotting,and immunofluorescence assay.Results In cultured human chondrocytes,treatment with IL-1β significantly decreased the cell viability,increased cell apoptosis rate,lowered miR-502-5p,IL-4,IL-10,and COL2A1 expressions,and enhanced IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 expressions(P<0.05),and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20％(P<0.05).Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 and lowered expressions of miR-502-5p,IL-4,IL-10,and COL2A1,and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor.Conclusion XFC can inhibit IL-1β-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.

Objectives:To evaluate the diagnostic value of echocardiography in unroofed coronary sinus syndrome(UCSS)with endocardial cushion defect(ECD). Methods:The echocardiographic data of 43 patients of UCSS with ECD who underwent surgical treatment in our hospital from July 2017 to May 2022 were retrospectively analyzed.The diagnostic accuracy was evaluated by comparing the echocardiographic findings with the intraoperative exploration results. Results:According to Kirklin and Barratt-Boyes classification,there were 26 cases of type Ⅰ(60.5%),9 cases of type Ⅱ(20.9%),2 cases of type Ⅲ(4.7%),4 cases of type Ⅳ(9.3%),and 2 cases of type Ⅲ combined with type Ⅳ(4.7%).There were 26 cases(60.5%)of partial ECD,7 cases(16.3%)of intermediate ECD,10 cases(23.3%)of total ECD.Twenty two cases(51.2%)were associated with single atrium.Twenty seven cases(62.8%)were associated with persistent left superior vena cava(PLSVC).Other coexisting complicated malformations were as follows:2 cases of double outlet of right ventricle,1 case of pulmonary atresia,1 case of total anomalous pulmonary venous connection,and 1 case of aplenia syndrome.The coexisting simple malformations included 4 cases of ostium secundum atrial septal defect,2 cases of ventricular septal defect,3 cases of patent ductus arterial,and 6 cases of patent foramen ovale.Other abnormalities included 5 cases of absence of hepatic segment of inferior vena cava,1 case of hypoplasia of right superior vena cava,1 case of absence of right superior vena cava,3 cases of cor triatriatum,1 case of isolated levocardia,1 case of mirror image dextrocardia,4 cases of right aortic arch.Of the 43 patients,30(69.8%)were correctly diagnosed by preoperative echocardiography and 13(30.2%)by intraoperative exploration.UCSS was misdiagnosed as inferior vena cava type sinus septal defect and PLSVC was missed in 1 case.UCSS was missed in 12 cases,and PLSVC was missed in 3 cases of them. Conclusions:Diagnosis UCSS with ECD by echocardiography is valuable and challenging.It is necessary to strengthen the understanding of the embryonic development and pathological anatomy characteristics of these malformations to improve the diagnostic accuracy.

Objective To investigate the mechanism that mediates the inhibitory effect of Xinfeng Capsule(XFC)on interleukin(IL)-1β-induced impairment of chondrocytes.Methods XFC-medicated serum was collected from SD rats with XFC gavage,and its optimal concentration for chondrocyte treatment was determined using Cell Counting Kit-8 assay and flow cytometry.Dual luciferase reporter analysis was performed to analyze the targeting relationship between miR-502-5p and TRAF2.In cultured human chondrocytes induced with IL-1β,the effects of transfection with miR-502-5p inhibitor and XFC-medicated serum,alone or in combination,on expression levels of IL-1β,tumor necrosis factor-α(TNF-α),IL-4,and IL-10 were examined with ELISA,and the changes in the expressions of collagen type Ⅱ alpha 1(COL2A1),matrix metalloproteinase 13(MMP13),adisintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),and miR-502-5p/TRAF2/NF-κB axis gene expression were detected using RT-qPCR,Western blotting,and immunofluorescence assay.Results In cultured human chondrocytes,treatment with IL-1β significantly decreased the cell viability,increased cell apoptosis rate,lowered miR-502-5p,IL-4,IL-10,and COL2A1 expressions,and enhanced IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 expressions(P<0.05),and these changes were significantly improved by treatment with XFC-medicated serum at the optimal concentration of 20％(P<0.05).Transfection of the chondrocytes with miR-502-5p inhibitor resulted in elevated expressions of IL-1β,TNF-α,ADAMTS5,MMP13,TRAF2,and NF-κB p65 and lowered expressions of miR-502-5p,IL-4,IL-10,and COL2A1,and XFC-medicated serum obviously reversed the effects of miR-502-5p inhibitor.Conclusion XFC can inhibit IL-1β-induced inflammatory response and ECM degradation in cultured human chondrocytes possibly by regulating the miR-502-5p/TRAF2/NF-κB axis.

Panax notoginseng is an ancient Chinese medicinal plant that has great clinical value in regulating cardiovascular disease in China. As a single component of panax notoginosides, notoginsenoside R1 (NGR1) belongs to the panaxatriol group. Many reports have demonstrated that NGR1 exerts multiple pharmacological effects in ischemic stroke, myocardial infarction, acute renal injury, and intestinal injury. Here, we outline the available reports on the pharmacological effects of NGR1 in ischemia-reperfusion (I/R) injury. We also discuss the chemistry, composition and molecular mechanism underlying the anti-I/R injury effects of NGR1. NGR1 had significant effects on reducing cerebral infarct size and neurological deficits in cerebral I/R injury, ameliorating the impaired mitochondrial morphology in myocardial I/R injury, decreasing kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in renal I/R injury and attenuating jejunal mucosal epithelium injury in intestinal I/R injury. The various organ anti-I/R injury effects of NGR1 are mainly through the suppression of oxidative stress, apoptosis, inflammation, endoplasmic reticulum stress and promotion of angiogenesis and neurogenesis. These findings provide a reference basis for future research of NGR1 on I/R injury.
Humans ; Reperfusion Injury/prevention & control* ; Inflammation ; China ; Apoptosis

Objective:To investigate the alterations in soft tissue morphology and thickness in the mid-face region of patients with cleft lip and palate (UCLP) secondary to maxillofacial deformity following Le Fort I osteotomy.Methods:A total of 22 patients (16 males and 6 females aged from 17 to 28 years with an average of 20 years) diagnosed with cleft lip and palate secondary to maxillofacial deformity were collected from the Wuhan University Hospital of Stomatology from July 2012 to August 2020. All patients underwent Le Fort I osteotomy. CBCT scans were obtained at T0 (3 days before surgery), T1 (7 days after surgery), and T2 (1 year after surgery). The Dolphin11.95 software and 3D Slicer software were utilized to measure and analyze the soft tissue near the mid-face osteotomy line. Differences in soft tissue thickness before and after surgery were compared.Results:Before and after the operation, the soft tissue thickness at P3, P5, P6, and P8 on the affected side was thicker than that on the healthy side, and the difference was statistically significant, with a P-value of <0.05. At P5, P6, P7, P8, and P9 below the osteotomy line at T2-T0, the degree of postoperative thinning on the affected side was more apparent than that on the healthy side, and there was statistical significance at P6 ( P<0.05). The postoperative soft tissue asymmetry in the Ck region was improved compared with the preoperative one. The preoperative average protruding of the affected side was 0.63 compared with the healthy side, and the postoperative value was 0.17. The preoperative and postoperative Mann-Whitney U tests showed significantly statistical difference. Conclusions:After Le Fort I osteotomy, the facial asymmetry of patients with unilateral cleft lip and palate secondary to maxillofacial deformity is improved. However, there is still a difference in the soft tissue thickness between the healthy side and the affected side, and the change in soft tissue thickness on the affected side is more significant than that on the healthy side.

Objectives To analyze the risk factors and their predictive value for postoperative hypoxemia in Type-A aortic dissection(TAAD).Methods A single-center retrospective study was conducted among 146 consecutive patients diagnosed as TAAD and undergone aortic arch surgery from January 2018 to June 2021 in Nanfang Hospital of Southern Medical University.According to the lowest postoperative PaO2/FiO2 ratio within 24 hours,the patients were classified into two groups:hypoxemia group(PaO2/FiO2≤200 mmHg)and non-hypoxemia group(PaO2/FiO2>200 mmHg).The difference of preoperative oxygen index,duration of mechanical ventilation and mortality in hospital were analyzed between the two groups.The independent risk factors for postoperative hypoxemia were evaluated by multivariate logistic regression and the predictive value was analyzed by receiver operator character(ROC)curves.Results For TAAD patients,the incidence of postoperative hypoxemia was 45.9%.Compared to non-hypoxemia group,hypoxemia group exhibited longer duration of mechanical ventilation(P<0.001)and longer intensive care unit(ICU)length of stay(P<0.05).Moreover,patients with hypoxemia presented higher mortality during hospital(P=0.011).Multivariate regression analysis identified BMI as independent risk factor(OR=1.701,P<0.001)and preoperation PaO2/FiO2 ratio as protective factors for postoperative hypoxemia in patients with TAAD(OR=0.987,P=0.004).Area under the ROC curve of BMI was 0.848,the optimal cut-off point of BMI was 25.8 kg/m2.Area under the ROC curve of pre-operation PaO2/FiO2 ratio was 0.808,the optimal cut-off point of preoperation PaO2/FiO2 ratio was 265 mmHg.Conclusions BMI higher than 25.8 kg/m2 is an independent risk factor and preoperation PaO2/FiO2 ratio higher than 265 mmHg is a protective factor for postoperative hypoxemia in patients with TAAD.Subjects with hypoxemia had longer duration of mechanical ventilation,ICU stay and higher mortality.

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

Head and neck squamous cell carcinoma (HNSCC), as the most common type (>90%) of head and neck cancer, includes various epithelial malignancies that arise in the nasal cavity, oral cavity, pharynx, and larynx. In 2020, approximately 878 ‍ 000 new cases and 444 000 deaths linked to HNSCC occurred worldwide (Sung et al., 2021). Due to the associated frequent recurrence and metastasis, HNSCC patients have poor prognosis with a five-year survival rate of 40%-50% (Jou and Hess, 2017). Therefore, novel prognostic biomarkers need to be developed to identify high-risk HNSCC patients and improve their disease outcomes.
Biomarkers, Tumor/genetics* ; Head and Neck Neoplasms/genetics* ; Humans ; Kaplan-Meier Estimate ; RNA ; Squamous Cell Carcinoma of Head and Neck ; Survival Analysis ; Survival Rate

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×10⁷/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.
Acute Lung Injury/therapy* ; Animals ; Bone Marrow ; Collagen/metabolism* ; Endotoxins ; Extracellular Matrix ; Lipopolysaccharides/adverse effects* ; Lung ; Male ; Malondialdehyde/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Mesenchymal Stem Cells/metabolism* ; Myosin Type II/metabolism* ; Pulmonary Fibrosis ; Rats ; Rats, Sprague-Dawley ; Saline Solution/metabolism* ; Superoxide Dismutase/metabolism*

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.
Child ; Male ; Female ; Humans ; Anemia, Diamond-Blackfan/genetics* ; Pediatric Obesity/complications* ; Glucocorticoids/therapeutic use* ; Prevalence ; Risk Factors ; Ribosomal Proteins/genetics* ; Mutation