Diffusion-weighted imaging of the orbit.

Orbital lesions compose a heterogeneous group of pathologies that often present with non-specific imaging findings on conventional magnetic resonance imaging (MRI) sequences (T1-and T2-weighted). Accordingly, the application of diffusion MRI offers an opportunity to further distinguish between lesions along this spectrum. Diffusion-weighted imaging (DWI) represents the simplest and most frequent clinically utilised diffusion imaging technique. Recent advances in DWI techniques have extended its application to the evaluation of a wider spectrum of neurological pathology, including orbital lesions. This review details the manifestations of select orbital pathology on DWI and underscores specific situations where diffusion imaging allows for increased diagnostic sensitivity compared to more conventional MRI techniques. These examples also describe preferred management for orbital lesions identified by DWI.

HMGN1 down-regulation in the diabetic kidney attenuates tubular cells injury and protects against renal inflammation via suppressing MCP-1 and KIM-1 expression through TLR4.

BACKGROUND: Renal tubular injury, accompanied by damaging inflammation, has been identified to drive diabetic kidney disease (DKD) toward end-stage renal disease. However, it is unclear how damage-associated molecular patterns (DAMPs) activate innate immunity to mediate tubular epithelial cell (TEC) injury, which in turn causes with subsequent sterile inflammation in diabetic kidneys. High mobility group nucleosome-binding protein 1 (HMGN1) is a novel DAMP that contributes to generating the innate immune response. In this study, we focused on determining whether HMGN1 is involved in DKD progression. METHODS: Streptozotocin (STZ)-induced diabetic mice model was established. Then we downrergulated HMGN1 expression in kidney with or without HMGN1 administration. The renal dysfunction and morphological lesions in the kidneys were evaluated. The expressions of KIM-1, MCP-1, F4/80, CD68, and HMGN1/TLR4 signaling were examined in the renal tissue. In vitro, HK2 cells were exposed in the high glucose with or without HMGN1, and further pre-incubated with TAK242 was applied to elucidate the underlying mechanism. RESULTS: We demonstrated that HMGN1 was upregulated in the tubular epithelial cells of streptozotocin (STZ)-induced type 1 and type 2 diabetic mouse kidneys compared to controls, while being positively correlated with increased TLR4, KIM-1, and MCP-1. Down-regulation of renal HMGN1 attenuated diabetic kidney injury, decreased the TLR4, KIM-1, and MCP-1 expression levels, and reduced interstitial infiltrating macrophages. However, these phenotypes were reversed after administration of HMGN1. In HK-2 cells, HMGN1 promoted the expression of KIM-1 and MCP-1 via regulating MyD88/NF-κB pathway; inhibition of TLR4 effectively diminished the in vitro response to HMGN1. CONCLUSIONS: Our study provides novel insight into HMGN1 signaling mechanisms that contribute to tubular sterile injury and low-grade inflammation in DKD. The study findings may help to develop new HMGN1-targeted approaches as therapy for immune-mediated kidney damage rather than as an anti-infection treatments.

[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

Importance of oxygen tension in human ovarian tissue in vitro culture.

STUDY QUESTION: Is there any difference between 20% and 5% oxygen (O2) tension in vitro culture (IVC) on the viability and quality of human follicles contained in cultured ovarian cortex? SUMMARY ANSWER: An O2 tension of 5% yields higher follicle viability and quality than does 20% O2 tension after 6 days of IVC. WHAT IS KNOWN ALREADY: The primordial follicle (PMF) pool resides within the ovarian cortex, where the in vivo O2 tension ranges between 2% and 8%. Some studies suggest that lowering O2 tension to physiological levels may improve in vitro follicle quality rates. STUDY DESIGN, SIZE, DURATION: This prospective experimental study included frozen-thawed ovarian cortex from six adult patients (mean age: 28.5 years; age range: 26-31 years) who were undergoing laparoscopic surgery for non-ovarian diseases. Ovarian cortical fragments were cultured for 6 days at (i) 20% O2 with 5% CO2 and (ii) 5% O2 with 5% CO2. Non-cultured fragments served as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cortical fragments were used for the following analyses: hematoxylin and eosin staining for follicle count and classification; Ki67 staining to evaluate PMF proliferation; cleaved caspase-3 immunostaining to identify follicle apoptosis; 8-hydroxy-2-deoxyguanosine and gamma-H2AX (γH2AX) immunolabeling to detect oxidative stress damage and DNA double-strand breaks (DSBs) in oocytes and granulosa cells (GCs); and ß-galactosidase staining to assess follicle senescence. Droplet digital PCR was also performed to further explore the gene expression of superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4) from the antioxidant defense system and cyclin-dependent kinase inhibitors (p21 and p16) as tissue senescence-related genes. MAIN RESULTS AND THE ROLE OF CHANCE: Apoptosis (P = 0.002) and follicle senescence (P < 0.001) rates were significantly lower in the 5% O2 group than in the 20% O2 group. Moreover, GCs in follicles in the 20% O2 group exhibited significantly (P < 0.001) higher oxidative stress damage rates than those in the 5% O2 group. DNA DSB damage rates in GCs of follicles were also significantly higher (P = 0.001) in the 20% O2 group than in the 5% O2 group. SOD2 expression was significantly greater in the 5% O2 group compared to the 20% O2 group (P = 0.04) and the non-cultured group (P = 0.002). Expression of p21 was significantly increased in both the 20% O2 (P = 0.03) and 5% O2 (P = 0.008) groups compared to the non-cultured group. Moreover, the 20% O2 group showed significantly greater p16 expression (P = 0.04) than the non-cultured group, while no significant variation was observed between the 5% O2 and no culture groups. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study focuses on improving follicle outcomes during the first step of ovarian tissue IVC, where follicles remain in situ within the tissue. The impact of O2 tension in further steps, such as secondary follicle isolation and maturation, was not investigated here. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that 5% O2 tension culture is a promising step toward potentially solving the problem of poor follicle viability after IVC. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR T.0064.22, CDR J.0063.20 and grant 5/4/150/5 awarded to M.M.D.). The authors have nothing to disclose.

[Identification and preliminary validation of potential biomarkers in the peripheral blood mononuclear cells of atopic dermatitis].

Objective: To explore the difference of peripheral blood mononuclear cells (PBMC) transcripts between atopic dermatitis (AD) and healthy controls, and to screen and preliminarily validate potential biomarkers of AD. Methods: From January 2021 to May 2022, blood samples from 9 AD patients and 10 healthy controls were collected from the Dermatology and Cosmetic Center of the Third Affiliated Hospital of Chongqing Medical University, ribonucleic acid-sequencing (RNA-seq) was used to determine the transcriptome and relative expression of PBMC, the differentially expressed genes (DEGs) were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction networks (PPI) analysis, and the potential biomarkers were identified by quantitative real-time PCR (qRT-PCR). Results: The age of patients in the AD group [M (Q1, Q3)] was 26.50 (22.75, 30.50) years old, and the course of disease [M (Q1, Q3)] was 15 (10, 20) years,and the age of the healthy control group [M (Q1, Q3)] was 37.00 (27.75, 40.25) years old. Compared with healthy controls, 1 044 DEGs were detected in PBMC samples in AD group, including 668 up-regulated genes and 376 down-regulated genes. Differential variable splicing (AS) showed that mutually exclusive exons (46.74%) and skipped exon (31.01%) accounted for a large proportion. GO and KEGG enrichment analysis revealed that AD is closely linked to DEGs implicated in the inflammatory response and cytokine interaction and signal pathway. Comprehensive enrichment analysis and PPI analysis selected the expression of 8 candidate genes (CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20, LY96), which was confirmed by qRT-PCR and were consistent with that of RNA-seq. Conclusions: CCL4, CCR3, CXCR5, NFKBIA, CXCL1, IL-1B, CCL20 and LY96 might be potential biomarkers of AD, participating in the occurrence and development of AD.

[Vaginal microbiota abnormalities in women with unexplained infertility and its treatment].

The vaginal microbiota is a complex and dynamic environment that plays an important role in the healthy reproduction of women. The mechanism of unexplained infertility is not yet clear, and the imbalance and low stability of vaginal microbiota may be related to unexplained infertility. Taking probiotic composite preparations to restore normal vaginal microbiota may be a safe and natural method for treating unexplained infertility. This article reviews the probiotic composite preparations used in the treatment of unexplained infertility both domestically and internationally, including the isolation site of the bacterial species, the use method of the composite preparation, the course of treatment, and the final therapeutic effect, aiming to provide a basis for the clinical application of probiotic composite preparations in the treatment of unexplained infertility.

Effect of Activated Immunocompetent Cells on the Content of Multipotent Stromal Cells in Splenic Transplants of CBA and CBA/N Mice Administered with Polyvinylpyrrolidone.

One day after intraperitoneal injection of polyvinylpyrrolidone (PVP) to recipient CBA and CBA/N mice, the count of multipotent stromal cells (MSC) in the 4-month-old splenic transplants was minimum in CBA/N→CBA/N group in comparison with the transplants of intact recipients (0.6 from the control level), but increased by 2.3, 3.2, and 3.7 times in CBA/N→CBA, CBA→CBA, and CBA→CBA/N groups, respectively. In the blood serum of recipient CBA/N mice with 4-month splenic transplants of CBA donors, the levels of some cytokines (IL-5, TNFα, and IL-2) was significantly increased 1 and 24 h after PVP injection in contrast to mice with bone marrow transplants, which attests to activation of the innate immunity mechanisms in this (splenic) transplantation variant. Probably, this phenomenon can be explained by the fact that the splenic transplants contain a sufficient number of CD+B-1a lymphocytes that can restore the response of recipient CBA/N mice to PVP. Thus, similar to bone marrow transplants [5], MSC count in splenic transplants increased only in groups, where the recipients were capable of responding to PVP. In other words, after injection of PVP to recipient mice, MSC counts in the spleen and bone marrow at this moment are determined by availability of activated immunocompetent cells. Overall, the novel data attest to close relationships between the stromal tissue of hematopoietic and lymphoid organs, on the one hand, and immune system, on the other.

[Analysis of time for diagnosis of nontuberculous mycobacterial lung disease and its associated factors in a tuberculosis-designated hospital in Shanghai].

Objective: To investigate the pathogenic characteristics, bacteriological diagnosis time and its associated factors among patients with nontuberculous mycobacterial (NTM) lung disease in a large tuberculosis-designated hospital in Shanghai from 2020 to 2021, in order to improve diagnosis efficiency and formulate precision treatment. Methods: On the basis of the Tuberculosis Database in Shanghai Pulmonary Hospital, NTM patients diagnosed by the Department of Tuberculosis between January 2020 and December 2021 were screened. Demographic, clinical and bacterial information were retrospectively collected. Chi-square test, paired-sample nonparametric test and logistic regression model were used to analyze the factors associated with the diagnosis time of NTM lung disease. Results: A total of 294 patients with bacteriologically confirmed NTM lung disease were included in this study, 147 males and 147 females with a median age of 61(46, 69) years. Of them, 227 (77.2%) patients had comorbidity of bronchiectasis. Species identification results showed that Mycobacterium Avium-Intracellulare Complex was the main pathogen of NTM lung disease (56.1%), followed by Mycobacterium kansasii (19.0%) and Mycobacterium abscessus (15.3%). Species such as Mycobacterium xenopi and Mycobacterium malmoense were rarely identified, accounting for a total proportion of only 3.1%. Positive culture rates for sputum, bronchoalveolar lavage fluid and puncture fluid were 87.4%, 80.3% and 61.5%, respectively. Paired-sample analysis showed that the positive rate of sputum culture was significantly higher than that of smear microscopy (87.1% vs. 48.4%, P<0.01), while no statistical difference was observed between sputum and bronchoalveolar lavage fluid on positive culture rate (78.7% vs. 77.3%, P>0.05). Patients with cough or expectoration were observed with 4.04-fold (95%CI 1.80-9.05) or 2.95-fold (95%CI 1.34-6.52) higher probability of positive sputum culture, compared to those without. Regarding bronchoalveolar lavage fluid, female or patients with bronchiectasis had a 2.82-fold (95%CI 1.16-6.88) or 2.38-fold (95%CI 1.01-5.63) higher probability to achieve a positive culture. The median time to diagnosis of NTM lung disease was 32 (interquartile range: 26-42) days. The results of multivariable analysis showed that patients with symptom of expectoration (aOR=0.48, 95%CI 0.29-0.80) needed a shorter diagnosis time in comparison with patients without expectoration. With Mycobacterium Avium-Intracellulare Complex as a reference, lung disease caused by Mycobacterium abscessus needed shorter diagnosis time (aOR=0.43, 95%CI 0.21-0.88), whereas those caused by rare NTM species were observed to require a longer diagnosis time (aOR=8.31, 95%CI 1.01-68.6). Conclusion: The main pathogen causing NTM lung disease in Shanghai was Mycobacterium Avium-Intracellulare Complex. Sex, clinical symptoms and bronchiectasis had an impact on the positive rate of mycobacterial culture. The majority of patients in study hospital were timely diagnosed. Clinical symptoms and NTM species were associated with the bacteriological diagnosis time of NTM lung disease.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

Creatine deficiency and heart failure.

Impaired cardiac energy metabolism has been proposed as a mechanism common to different heart failure aetiologies. The energy-depletion hypothesis was pursued by several researchers, and is still a topic of considerable interest. Unlike most organs, in the heart, the creatine kinase system represents a major component of the metabolic machinery, as it functions as an energy shuttle between mitochondria and cytosol. In heart failure, the decrease in creatine level anticipates the reduction in adenosine triphosphate, and the degree of myocardial phosphocreatine/adenosine triphosphate ratio reduction correlates with disease severity, contractile dysfunction, and myocardial structural remodelling. However, it remains to be elucidated whether an impairment of phosphocreatine buffer activity contributes to the pathophysiology of heart failure and whether correcting this energy deficit might prove beneficial. The effects of creatine deficiency and the potential utility of creatine supplementation have been investigated in experimental and clinical models, showing controversial findings. The goal of this article is to provide a comprehensive overview on the role of creatine in cardiac energy metabolism, the assessment and clinical value of creatine deficiency in heart failure, and the possible options for the specific metabolic therapy.

NMR and dynamic light scattering give different diffusion information for short-living protein oligomers. Human serum albumin in water solutions of metal ions.

Diffusive behavior of human serum albumin (HSA) in the presence of Mg2+ and Cu2+ ions was studied by pulsed field gradient nuclear magnetic resonance (PFG NMR) and dynamic light scattering (DLS). According to NMR data yielding measurements of HSA self-diffusion coefficient, a weighted average of the protein monomers and oligomers diffusion mobility in the presence of metal ions was observed. While the short-time collective diffusion measured by DLS showed one type of diffusing species in ion-free HSA solution and two molecular forms of HSA in the presence of metal ions. The light intensity correlation function analysis showed that HSA oligomers have a limited lifetime (lower limit is about 0.4 ms) intermediate between characteristic time scales of PFG NMR and DLS experiments. For a theoretical description of concentration dependence of HSA self- and collective diffusion coefficients, the phenomenological approach based on the frictional formalism of non-equilibrium thermodynamics was used (Vink theory), allowing analysis of the solvent-solute and solute-solute interactions in protein solutions. In the presence of metal ions, a significant increase of HSA protein-protein friction coefficient was shown. Based on theoretical analysis of collective diffusion data, the positive values of second virial coefficients A2 for HSA monomers were obtained. The A2 values were found to be higher for the HSA with metal ions compared with the ion-free HSA solution. This is due to the more pronounced contribution of repulsion in protein-protein interactions of HSA monomers in the presence of Mg2+ and Cu2+ ions.

Melting of crystallites in a solid porous matrix and the application limits of the Gibbs-Thomson equation.

A thermodynamic model is proposed to describe the melting of lamellar crystallite in a solid medium. This model includes a modification of the Gibbs-Thomson equation to make it applicable to the above-mentioned crystallites. The need for such modification is supported experimentally by studying the impact of the surroundings on the melting point of the crystallites. In particular, the application of the model to nanocrystals in open-porous systems makes it possible to determine the analytical relations for the melting point, the heat of melting, and the inverse effective size of the pores. The fitting of the experimental data with these functional relations then allows for the calculation of the nanocrystalline density, pressure in the nanocrystal, and difference in the surface tension coefficients at the nanocrystal-matrix interface and melt-matrix interface, as well as the difference in the surface entropies per unit area at the nanocrystal-matrix and melt-matrix interfaces.

Effects of the bovine SLICK1 mutation in PRLR on sweat gland area, FOXA1 abundance, and global gene expression in skin.

The SLICK1 mutation in the prolactin receptor (PRLR) results in a short-hair coat and increased ability to regulate body temperature during heat stress. It is unclear whether the mutation affects capacity for sweating. The objective of this observational study was to evaluate whether the SLICK1 mutation in PRLR alters characteristics of skin related to sweat gland abundance or function. Skin biopsies from 31 Holstein heifers, including 14 wild-type (SL-/-) and 17 heterozygous slick (SL+/-), were subjected to histological analysis to determine the percent of the surface area of skin sections that are occupied by sweat glands. We detected no effect of genotype on this variable. Immunohistochemical analysis of the forkhead transcription factor A1 (FOXA1), a protein essential for sweating in mice, from 6 SL-/- and 6 SL+/- heifers indicated twice as much FOXA1 in sweat glandular epithelia of SL+/- heifers as in SL-/- heifers. Results from RNA sequencing of skin biopsies from 5 SL-/- and 7 SL+/- heifers revealed few genes that were differentially expressed and none that have been associated with sweat gland development or function. In conclusion, results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, but do show that functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1, are modified by inheritance of the mutation in PRLR.

[Naringenin inhibits thoracic aortic aneurysm formation in mice with Marfan syndrome].

OBJECTIVE: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. METHODS: To validate the effect of naringenin, Fbn1C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. RESULTS: Six-week-old Fbn1C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1C1039G/+ mice with established thoracic aortic aneurysms [Fbn1C1039G/+ vs. Fbn1C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-ß (TGF-ß) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to ß-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-ß signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-ß downstream genes. Besides, the serum level of TGF-ß was also decreased by naringenin in the Fbn1C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-ß, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-ß level by inhibiting the activation of platelet. CONCLUSION: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-ß signaling.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[Efficiency and safety of peptide receptor radionuclide therapy in the treatment of metastatic neuroendocrine tumors].

The clinical data of 14 patients with neuroendocrine tumors who received Peptide Receptor Radionuclide Therapy (PRRT) from December 2018 to May 2021 were retrospectively analyzed. Among them, 2 patients demonstrated proprogressive disease, 2 patients had partial response, and 10 patients had stable disease. Grade 1-2 myelosuppression occurred in 5 patients. and 1 patient became grade 3 myelosuppression，which recovered to grade 2 after symptomatic treatment. No grade 2 or higher treatment-related renal toxicity was observed in any of the patients. PRRT is efficacy and no significant side effects for unresectable metastatic neuroendocrine tumors.

[Research advances in the application of bone metabolic markers in children's diseases associated with growth and development].

The incidence of children's growth and development diseases such as rickets, obesity, dwarfism and precocious puberty has increased year by year recently. The occurrence and development of these diseases are often closely related to children's malnutrition and endocrine disorders. Plenty of studies have indicated that bone is not only the structural scaffold of human body, but also an important endocrine and hormone target organ. As a series of substances closely related to bone formation and bone resorption, the levels of bone metabolic markers have been confirmed to change in the course of many children's growth and development diseases. The characteristics, classification and application of bone metabolism markers in children's growth and development related diseases was summarized and commented in this article in order to provide reference for the prevention, early diagnosis and treatment effect monitoring of children's growth and development diseases.

Experimental Correction of Homeostasis Changes during Alloxan-Induced Diabetes by Implantation of Islet Cells Cultured in Fibrous TiNi-Based Scaffold.

The use of fibrous scaffolds made of titanium nickelide and carrying islet cells (IC) after a course of alloxan administration was studied in vivo. Scanning electron microscopy showed good adhesion of IC in the pore space of the scaffolds. In 28 days, mature tissue comprising both cellular and fibrous components filled the inner space of the scaffold by 90%. The advantage of intraperitoneal implantation of IC in vitro seeded in fibrous titanium nickelide scaffolds in comparison with injection of IC (6×105 cells) to Wistar rats was demonstrated in the dynamics of pancreatic function recovery (normalization of blood glucose and glycosylated hemoglobin concentrations by day 21 of the experiment), regeneration of the white hematopoietic lineage cells, and lengthening (by 2 times) of the lifespan of animals with alloxan-induced diabetes. Injection of IC improved rat survival by only 40%. Thus, the hybrid tissue-engineered construct (fibrous titanium nickelide scaffold+IC) is biocompatible when administered intraperitoneally, stimulates regeneration in rats with alloxan-induced diabetes, improves blood glucose utilization processes, and restores suppressed leukopoiesis. It is assumed that hepatocytes can be the main target cells of the hybrid tissue-engineering construct.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.

Aim      To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods  Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion      This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.