Research progress in risk factors of post-transplantation diabetes mellitus / 器官移植

Solid organ transplantation has significantly prolonged the survival of patients with end-stage diseases. However, long-term use of immunosuppressants will increase the risk of post-transplantation diabetes mellitus (PTDM) in the recipients, thereby elevating the risk of infection, cardiovascular disease and death. In recent years, with persistent improvement of diagnostic criteria of PTDM, clinicians have deepened the understanding of this disease. Compared with type 2 diabetes mellitus, PTDM significantly differs in pathophysiological characteristics and clinical progression. Hence, different treatment strategies should be adopted. Early identification of risk factors of organ transplant recipients, early diagnosis and intervention are of significance for improving the quality of life of recipients, prolonging the survival of grafts and reducing the fatality of recipients. Therefore, the diagnosis, incidence and risk factors of PTDM were reviewed in this article, aiming to provide reference for clinicians to deliver prompt diagnosis and intervention for PTDM.

Extract of Cimicifuga racemosa (L.) Nutt protects ovarian follicle reserve of mice against in vitro deleterious effects of dexamethasone

The present study aims to investigate if Cimicifuga racemosa (L.) Nutt extract (CIMI) reduces deleterious effects of dexamethasone (DEXA) in ovaries cultured in vitro. Mouse ovaries were collected and cultured in DMEM+ only or supplemented with 5 ng/mL of CIMI, or 4 ng/mL DEXA, or both CIMI and DEXA. The ovaries were cultured at 37.5°C in 5% CO2 for 6 days. Ovarian morphology, follicular ultrastructure, and the levels of mRNA for Bax, Bcl-2, and Caspase-3 were evaluated. The results showed that DEXA reduced the percentage of morphologically normal follicles, while CIMI prevented the deleterious effects caused by DEXA. In addition, DEXA negatively affected the stromal cellular density, while CIMI prevented these adverse effects. Ovaries cultured with DEXA and CIMI showed similar levels of mRNA for Bax, Bcl-2, and Caspase-3 compared to those cultured in control medium, while ovaries cultured with DEXA had increased expression of the above genes. Additionally, the ultrastructure of the ovaries cultured with CIMI was well preserved. Thus, the extract of CIMI was able to prevent the deleterious effects caused by DEXA on cultured mouse ovaries.

Dental erosion caused by glucocorticoid therapy in a patient with optic neuritis: a case report / 华西口腔医学杂志

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.

A case of acute cholestatic jaundice after hormone treatment of Graves disease with upper respiratory tract infection / 中国综合临床

Cholestatic jaundice is rare in patients with Graves' disease and is generally considered to be a complication of Graves' disease or an adverse reaction to methimazole. We report a case of acute cholestatic jaundice caused by Graves' disease complicated with upper respiratory tract infection in Jinan Central Hospital. After timely treatment with glucocorticoid, the jaundice quickly subsided and the liver function gradually returned to normal. We believe that Graves' disease combined with upper respiratory tract infection can lead to cholestatic jaundice, the pathogenesis of which may be immune dysfunction, and glucocorticoid therapy is beneficial to the regression of jaundice.

Advances in Hormone Replacement Therapy for Adult Adrenal Insufficiency / 罕见病研究

Adrenal insufficiency is a disease characterized by insufficient secretion of adrenocortical hormones, usually treated with glucocorticoid replacement therapy. The routine drugs have two forms-short-acting and long-acting. The shorter one should be taken 2-3 times a day resulting hormone level of patients fluctuating greatly within a day. Although long-acting drugs reduce the frequency of administration, it is easy to lead to excessive replacement, resulting in adverse effects on metabolism. New alternative treatments for adult patients have emerged, including modified-release hydrocortisone and hydrocortisone subcutaneous infusion pumps. In this review, we briefly introduce these new therapies, emphasizing the pharmacodynamics and pharmacokinetics of the replacement, the effects on metabolism and drug safety, aiming at contributing to the future clinical practice.

Network meta-analysis of the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease / 中国药房

OBJECTIVE To evaluate the efficacy and safety of different drug regimens in the treatment of children with Kawasaki disease， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from the Cochrane Library， Medline， Embase， CINAHL， Web of Science， ProQuest， Google Scholar， CNKI， Wanfang Data， Baidu academic database， World Health Organization International Clinical Trials Registration Platform and ClinicalTrials. gov， randomized controlled trials （RCTs） about intravenous immunoglobulin （IVIG）+glucocorticoid or cyclosporine or tumor necrosis factor-alpha （TNF-α） blocker （trial group） versus standard IVIG therapy （control group） were collected from the establishment of the database to Feb. 28th， 2023. After screening the literature， extracting data， and evaluating the quality of the literature， Stata 14.2 software was used for network meta-analysis. RESULTS Ten RCTs with a total of 1 323 participants involving six measures were included： standard IVIG therapy， glucocorticoid therapy，cyclosporine therapy， TNF- α blocker therapy， remedial glucocorticoid therapy and remedial TNF- α blocker therapy. Results of network meta-analysis showed that the incidence of coronary artery aneurysms （CAA） at 4-8 weeks was significantly lower in patients receiving glucocorticoid therapy than receiving standard IVIG therapy and TNF-α blocker therapy. The incidences of CAA at 4-8 weeks in children treated with remedial glucocorticoid therapy and remedial TNF- α blocker therapy were significantly higher than those treated with glucocorticoid therapy； there was no significant difference in the incidence of CAA at 4-8 weeks among other interventions （P＞ 0.05）； network meta-order of the incidence was glucocorticoid therapy＜cyclosporine therapy＜standard IVIG therapy＜remedial TNF-α blocker therapy＜remedial glucocorticoid therapy＜TNF-α blocker therapy. The incidence of initial IVIG resistance in children receiving cyclosporine therapy was significantly lower than those receiving standard IVIG therapy； there was no significant difference in the incidence of initial IVIG resistance among other interventions （P＞0.05）； network meta-order of the incidence was cyclosporine therapy＜glucocorticoid therapy＜TNF-α blocker therapy＜standard IVIG therapy. There was no significant difference in the incidence of ADR among different interventions （P＞0.05）； network meta-order of the incidence was remedial TNF-α blocker therapy＜TNF-α blocker therapy＜standard IVIG therapy＜glucocorticoid therapy＜cyclosporine therapy. CONCLUSIONS Glucocorticoid therapy at the initial treatment can significantly reduce the risk of CAA at 4-8 weeks in children with Kawasaki disease； cyclosporine has a significant effect on improving initial IVIG resistance， and the use of TNF-α blocker in the remedial stage may have the lowest incidence of adverse reactions.

Mechanism of Artemisia annua L. in GIOP with kidney-yin deficiency based on network pharmacology / 药学实践杂志

Objective To predict and preliminarily verify the potential targets and related signaling pathways of Artemisia annua L. in treating glucocorticoid-induced osteoporosis (GIOP) with kidney-yin deficiency by network pharmacology and in vitro experiments. Methods The pharmacological targets of Artemisia annua L. were obtained from TCMSP database and were converted to gene names through Uniprot database. The target genes of GIOP with kidney-yin deficiency were obtained from GeneCards database, OMIM database and Drugbank database, and the common target genes were obtained by cross analysis with drug target gene. Protein-protein interaction (PPI) network was constructed by String database, and visualization analysis and core targets screening were performed by Cytoscape 3.9.0. All common targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis through Metascape database. Finally, the prediction results were verified by in vitro experiments. Results Ninety-eight targets of Artemisia annua L. to GIOP with kidney-yin deficiency were screened, including 17 core genes. The results of GO and KEGG functional enrichment analysis indicated that Artemisia annua L. treating GIOP with kidney-yin deficiency was related to biological processes such as hormonal response, positive regulation of cell death and extracellular stimulation response, et al, as well as signaling pathways such as PI3K/AKT, AGE/RAGE, MAPK and IL-17 et al. The number of genes enriched in PI3K/AKT signaling pathway was the largest. In vitro experiment results showed that Artemisia annua L. promoted the proliferation of osteoblasts damaged by dexamethasone (DEX), increased alkaline phosphatase activity, activated PI3K/AKT pathway, and promoted the phosphorylation of AKT. Conclusion Artemisia annua L. treating GIOP with kidney-yin deficiency has the characteristics of multi-targets and multi-pathway, which could promote the proliferation and differentiation of osteoblasts through multiple pathways. The PI3K/AKT signaling pathway is an important pathway. Artemisia annua L. treating GIOP with kidney-yin deficiency might be related to its ability to promote the PI3K/AKT signaling pathway and promote the phosphorylation of AKT.

Influence of GLCCI1 gene rs37973 polymorphism on the efficacy of ICSs in the treatment of asthma-chronic obstructive pulmonary disease overlap / 中国药房

OBJECTIVE To investigate the association between the functional GLCCI1 gene rs37973 polymorphism and inhaled corticosteroids （ICSs） response in patients with asthma-chronic obstructive pulmonary disease overlap （ACO）. METHODS Totally 173 newly diagnosed ACO patients were recruited from Shanghai Pudong New Area People’s Hospital during April 1st， 2019 to December 31st， 2020. All patients were treated with Salmeterol fluticasone inhalation powder， twice a day， for 24 weeks. The genotype of rs37973 locus was determined， and lung function indicators [forced expiratory volume in one second （FEV1）， FEV1/forced vital capacity （FVC）， the percentage of FEV1 to expected value （FEV1%pred）]， and lung function improvement （ΔFEV1 and ΔFEV1%pred） were all detected. RESULTS Totally 111 patients completed the whole 24-week follow-up and lung function detection. Among them， there were 42 cases of AA genotype， 52 cases of AG genotype， and 17 cases of GG genotype. After 12， 24 weeks of treatment， lung function indexes of patients were significantly better than baseline lung function indexes before treatment （P＜0.05）. After 24 weeks of treatment， ACO patients with AA and AG genotypes showed significantly better lung function improvement than GG genotype， and ΔFEV1%pred of AA genotype was significantly better than AG genotype （P＜ 0.05）. After 12， 24 weeks of treatment， the improvement of lung function in patients with a smoking history ≤20 pack year was significantly better than those with a smoking history ＞20 pack year， and among patients with a smoking history ≤20 pack year， only AA genotype had significantly better FEV1%pred than AG genotype （P＜0.05）. After 12 weeks of treatment， among patients with a smoking history ＞20 pack year， the improvement of lung function in AA genotype and AG genotype was significantly better than GG genotype， and the FEV1%pred in AA genotype was significantly better than AG genotype （P＜0.05）. After 24 weeks of treatment， the improvement of lung function of AA genotype and AG genotype was significantly better than GG genotype （P＜0.05）. CONCLUSIONS GG genotype of GLCCI1 gene rs37973 locus is associated with the poor treatment response to ICSs in patients with ACO， especially in patients with smoking history ＞20 pack year.

Clinical characteristics and treatment prognosis of ocular toxocariasis / 中华眼底病杂志

Objective:To observe the clinical characteristics and treatment prognosis of patients with ocular toxocariasis (OT).Methods:A retrospective clinical trial. From March 2018 to September 2021, 40 eyes of 40 OT patients diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. All patients underwent best corrected visual acuity (BCVA) and scanning laser ophthalmoscope (SLO) examination. Color Doppler ultrasound flow imaging (CDFI), fluorescein fundus angiography (FFA) and optical coherence tomography (OCT) were performed in 25, 26 and 26 eyes, respectively. Among the 40 patients, there were 23 males (57.5%, 23/40) and 17 females (42.5%, 17/40). All patients were monocular. Thirty patients (75.0%, 30/40) were younger than 18 years old, with the mean age of (9.60±0.60) years. Ten patients (25.0%, 10/40) were great than or equal to 18 years old, with the mean age of (34.60±4.52) years. Thirty-three patients (82.5%, 33/40) lived in rural areas for a long time. There were 27 patients (67.5%, 27/40) with a history of contact with dogs and cats. In 40 eyes, peripheral granuloma (peripheral type), posterior pole granuloma (posterior pole type), vitreous opacity similar to endophthalmitis (turbid type) and hybrid type were 18(45.0%, 18/40), 11(27.5%, 11/40), 6(15.0%, 6/40) ang 5(12.5%,5/40), respectively. All patients were treated with drugs and/or surgery after definite diagnosis. There were 28 eyes of peripheral type, posterior pole type and hybrid type, 17 eyes were treated with surgery and 11 eyes with drug treatment, respectively. Five eyes with turbid type were only treated with drugs. In 40 patients, 33 patients participated in follow-up. The follow-up time after treatment was (18.78±9.44) months. The improvement of BCVA was observed. The number of eyes with different BCVA before and after treatment was compared by χ2 test or Fisher's test. Results:At the first visit, the BCVA ranged from light perception to 0.6, including 20 eyes with BCVA <0.1, 13 eyes with BCVA 0.1-0.3, and 7 eyes with BCVA >0.3. The posterior vitreous anterior limiting membrane was thickened in 24 eyes (60.0%, 24/40). There were 27 eyes (67.5%, 27/40) with lamellar vitreous opacity and 22 eyes (55.0%, 22/40) with peripheral/posterior pole granulomas. Among 25 eyes examined by CDFI, 14 eyes (56.0%, 14/25) showed characteristic stratified or diffuse opacity in vitreous body. Of the 26 eyes examined by FFA, 15 eyes (57.7%, 15/26) had "fern-like" leakage of retinal capillaries, and the lesion had a patchy non-perfused area. In 26 eyes examined by OCT, epiretinal membrane, cystoid macular edema and vitreoretinal traction were 8 (30.8%, 8/26), 5 (19.2%, 5/26) and 2 (7.7%, 2/26) eyes, respectively. At the last follow-up, compared with before treatment, the BCVA of 5 eyes with turbid type increased, and the difference was statistically significant ( P<0.05). In 28 eyes with peripheral type, posterior pole type and hybrid type, 17 eyes with surgical treatment improved BCVA, and the difference was statistically significant ( χ2=6.258, P<0.05). In 11 eyes only treated with drugs, BCVA remained unchanged, and the difference was not statistically significant ( χ2=0.594, P>0.05). Conclusions:OT patients are mostly children; retinal granulomas, gray-white hyperplastic membrane behind lens or vitreous stratified opacity are specific characteristics. OT is mainly treated by glucocorticoid drugs and vitrectomy.

A case report of moyamoya disease in a pedigree with glucocorticoid-remediable aldosteronism / 中华内分泌代谢杂志

We report a family of glucocorticoid-remediable aldosteronism (GRA). A 20-year-old man presented with early-onset hypertension accompanied by hypokalemia was admitted to our hospital. Clinical data and family history were collected. Following genetic analyses with PCR and Sanger sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located in 264-380 nucletide, which was considered as GRA. There were 4 cases of GRA in the family, the average age of onset was 28 years, and all had different degrees of hypertension. Among them, the proband′s uncle suffered from moyamoya disease and died 6 months later due to sudden cerebral hemorrhage. In order to improve the understanding of this rare disease, the pathogenesis, biochemical profiles, diagnosis and treatment of GRA were summarized and analyzed.

The survival, complications and prognosis of the extremely preterm infants / 中国新生儿科杂志

Objective:To study the complications and prognosis of extremely premature infants(EPIs) with gestational age (GA) <28 w.Methods:From January 2016 to December 2020, EPIs with GA <28 w admitted to NICU of our hospital were retrospectively studied. Clinical data of the infants and their mothers during pregnancy were reviewed. According to the prognosis, the infants were assigned into the survival group, the death group and the withdrawal group. According to GA, the infants were assigned into <26 w goup, 26~26 +6 w group, ≥27 w group. According to birth weight (BW), the infants were assigned in to ≤750 g group, 750~999 g group and ≥1 000 g group. SPSS 26.0 was used for data analysis. Results:A total of 265 EPIs were included, 122 (46.0%) in the survival group, 47 (17.7%) in the death group and 96 (36.2%) in the withdrawal group. GA and BW of the survival group were significantly higher than the death group and the withdrawal group ( P<0.05). The incidences of tracheal intubation (92.2%) and pulmonary hemorrhage (42.2%) in the death group were the highest among the three groups. The survival group had the highest application of prenatal glucocorticoids (80.3%) and pulmonary surfactants (99.2%) ( P<0.05). In the survival group, the top 3 common complications were bronchopulmonary dysplasia (BPD) (68.0%), pulmonary infections (65.6%) and neonatal sepsis (34.4%). The survival rate increased with GA and BW. Conclusions:The survival rate of EPIs is closely correlated with GA and BW. EPIs with pulmonary hemorrhage and tracheal intubation have poor prognosis. Prenatal glucocorticoids and pulmonary surfactant may improve clinical outcome. BPD and pulmonary infections are common complications of surviving EPIs.

Familial glucocorticoid deficiency caused by the NNT gene mutation: a case report and literature review / 中华实用儿科临床杂志

The clinical data, diagnose and treatment of a child with familial glucocorticoid deficiency (FGD) caused by the NNT gene mutation who was treated in the Department of Endocrinology, Children′s Hospital Affiliated to Nanjing Medical University in November 2014 were retrospectively analyzed.The female child with 1 year and 5 months old presented with 6 months of skin pigmentation.Laboratory examinations showed decreased cortisol and increased adrenocorticotropic hormone.During the follow-up period, she developed convulsions and precocious puberty.Whole exome sequencing revealed that the patient carried a homozygous mutation c. 1054G > A (p.G352R) in exon 8 of the NNT gene, which was a newly reported gene mutation.Domestic cases of FGD caused by the NNT gene mutation has never been reported yet.Through literature review of a total of 40 reported children with FGD caused by the NNT gene mutation, typical manifestations included skin pigmentation, hypoglycemia and seizures, alongside mineralocorticoid deficiency, precious puberty, abnormal male gonadal development, thyroid diseases and heart diseases.

Clinical study of Tiaogan Lifei Decoction on improving the level of symptom control in asthmatic patients with moderate and high dose glucocorticoid inhalation / 国际中医中药杂志

Objective:To investigate the effects of Tiaogan Lifei Decoction on the level of symptom control in patients with bronchial asthma (asthma) treated with moderate and high dosage inhaled glucocorticoids (ICS).Methods:Randomized double-blind placebo controlled prospective study was used. Totally 90 patients with asthma (liver lung disharmony, wind phlegm blocking collateral syndrome) using moderate and high dosage ICS who met the inclusion criteria from January 2020 to December 2021 in Chaoyang District Hospital of Traditional Chinese Medicine in Beijing were divided into two groups according to random number table method, with 45 cases in each group. On the basis of using the original dosage of ICS, the treatment group used Tiaogan Lifei Decoction, while the control group used Tiaogan Lifei Decoction simulant. The course of treatment was 12 weeks. TCM symptom score of both group before and after the treatment was detected; asthma control test (ACT) was used to assess the effects of asthma on the patients; St George's Hospital Respiratory Questionnaire (SGRQ) was used to assess patients' quality of life; the peak expiratory flow rate (PEF) was measured with a peak expiratory flow meter. 2 ml of venous blood was collected for eosinophil (EOS) detection, and the serum allergen specific IgE level was determined by ELISA. The adverse reactions were observed during the treatment and the clinical efficacy was evaluated.Results:During the test, 3 cases and 2 cases in the treatment group and control group lost prevention respectively. 3 cases in the treatment group and 6 cases in the control group withdrew from the trial because of the aggravation of symptoms and the need to increase the dosage of ICS. The total effective rate in the treatment group was 78.6% (33/42), and that in the control group was 55.8% (24/43), with statistical significance ( χ2=4.98, P=0.026). After treatment, the scores of daily activities, early awakening, control and total scores in the treatment group were higher than those in the control group ( t values were 1.76, 1.99, 2.00, 2.69, respectively, P<0.01 or P<0.05); after treatment, the scores of cough, chest tightness, active wheezing, upset, pharyngeal itch and total score in the treatment group were lower than those in the control group ( t values were -5.89, -6.01, -5.66, -4.27, -6.67, -9.05, respectively, P<0.01); SGRQ score in the treatment group was lower than that of the control group ( t=-7.19, P<0.01). No serious adverse reactions occurred during treatment in the two groups. Conclusion:Tiaogan Lifei Decoction is helpful to improve the symptom control level of asthma patients who are using ICS, and effectively improve the quality of life of patients with asthma of liver lung disharmony and wind phlegm obstructing collaterals syndrome.

Mechanism of action of glucocorticoid receptors in the growth of hepatoma cells / 国际肿瘤学杂志

The glucocorticoid receptor (GR) plays a critical role in signal transduction, expression of related genes and apoptosis of cancer cells. Hepatocellular carcinoma is characterized by high aggressiveness and mortality. In the exploration of the relationship between GR and hepatocellular carcinoma, numerous studies have shown that GR has an inhibitory effect on the growth of hepatocellular carcinoma cells, which provides new ideas and methods for the clinical application of GR in the treatment of hepatocellular carcinoma.

Intervention effect and mechanism of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis mice / 中国药房

OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by 节作用。E-mail：57667478@qq.com HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4 （IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜ 0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）. CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.

Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics / 中国骨伤

OBJECTIVE@#To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics.@*METHODS@#Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis.@*RESULTS@#Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway.@*CONCLUSION@#Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort / 中国修复重建外科杂志

OBJECTIVE@#To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure.@*METHODS@#Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described.@*RESULTS@#The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group.@*CONCLUSION@#The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Adjunctive corticosteroid therapy in patients with pulmonary tuberculosis

SUMMARY OBJECTIVES: In tuberculosis treatment, corticosteroids are used as adjuvants, especially in meningeal/pericardial tuberculosis. In other forms of the disease, especially in severe tuberculosis requiring mechanical ventilation, its use is controversial. The aim of the present study is to assess whether the use of corticosteroids in the treatment of pulmonary tuberculosis patients in mechanical ventilation is associated with in-hospital mortality. METHODS: This is a retrospective cohort study. Tuberculosis patients >18 years requiring mechanical ventilation, admitted to the emergency department or intensive care unit, were included. Data on corticosteroid use and mortality were collected. RESULTS: In total, 467 patients were included in the analysis; 399 used corticosteroids and 68 were noncorticosteroid users. The mortality rate was higher among corticosteroid users (59.9%) than in noncorticosteroid users (41.2%) (p=0.010). The total dose of corticosteroid in prednisone equivalents was not different between survivors and nonsurvivors (median [interquartile range]: 80 mg [5-56.6 mg] vs. 80 mg [50-135 mg]; p=0.881). CONCLUSIONS: Tuberculosis patients in mechanical ventilation who used corticosteroids had a higher mortality rate than those who did not use corticosteroids. The role of corticosteroids in pulmonary tuberculosis, especially in critically ill patients, remains unclear and needs further evaluation in prospective studies.

Central adrenal insufficiency: who, when, and how? From the evidence to the controversies - an exploratory review

ABSTRACT Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated.

Abordagem da hiperplasia adrenal congênita pela deficiência da enzima 21-hidroxilase em crianças e adolescentes: revisão / Management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency in children and adolescents: review

Objetivo: Descrever o diagnóstico e manejo clínico da deficiência da 21-hidroxilase (D-21OH), no contexto atual de inclusão da doença nos programas de triagem neonatal, bem como características genéticas, fisiopatológicas e manifestações na infância e adolescência. Fonte de Dados: Revisão integrativa realizada nas bases de dados MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science nos últimos vinte anos, em língua inglesa e portuguesa; população-alvo: crianças da primeira infância à adolescência; com o uso dos termos "triagem neonatal", "hiperplasia adrenal congênita", "deficiência da 21-hidroxilase", "glucocorticoide" e "polimorfismos do gene NR3C1". Síntese de Dados: A hiperplasia adrenal congênita (HAC) constitui um grupo de doenças caracterizadas por deficiências enzimáticas na esteroidogênese do córtex adrenal. A D-21OH é responsável por 95% dos casos e, se não tratada precocemente, pode levar ao óbito no período neonatal em sua forma clássica. A triagem neonatal para a HAC consiste na dosagem do precursor 17-hidroxiprogesterona (17OHP) no sangue de recém-nascidos, permitindo rápida confirmação diagnóstica e instituição da terapêutica. A implantação da triagem neonatal constitui um avanço, mas o controle dos pacientes pediátricos com D-21OH é complexo e deve ser sempre individualizado. Conclusão: A instituição dos programas de triagem neonatal para HAC tem trazido benefícios para o prognóstico das crianças com D-21OH. Seu manejo é multiprofissional, individualizado e ainda um desafio mesmo para o especialista. Ampla divulgação do conhecimento sobre a doença é desejável para permitir melhor condução dessas crianças, especialmente de meninas com a doença que apresentam genitália atípica.

Objective: To describe the diagnosis and clinical management of 21-hydroxylase deficiency (21OH-D), in the current context of including the disease in neonatal screening programs, as well as genetic, pathophysiological characteristics, and manifestations in childhood and adolescence. Data Source: Integrative review performed in MEDLINE (PubMed), LILACS (BVS), Scopus, Web of Science databases in the last twenty years, in English and Portuguese; target population: children from early childhood to adolescence; with the use of the terms "neonatal screening"; "congenital adrenal hyperplasia"; "21-hydroxylase deficiency"; "glucocorticoid"; "polymorphisms of the NR3C1 gene". Data Synthesis: Congenital adrenal hyperplasia (CAH) is a group of diseases characterized by enzyme deficiencies in adrenal cortex steroidogenesis. 21OH-D is responsible for 95% of cases and, if not treated early, can lead to death in the neonatal period in its classic form. Neonatal screening for CAH consists of measuring the precursor 17-hydroxyprogesterone (17OHP) in the blood of newborns, allowing rapid diagnostic confirmation and institution of therapy. The implementation of neonatal screening is an advance, but the control of pediatric patients with 21OH-D is complex and must always be individualized. Conclusion: The institution of newborn screening programs for CAH has benefits for the prognosis of children with 21OH-D. Its management is multi-professional, individualized and still a challenge even for the specialist. Wide dissemination of knowledge about the disease is desirable to allow better management of these children, especially girls with the disease who have atypical genitalia.