Efecto modulador de los glucocorticoides sobre la angiogénesis mediada porPI3K/Akt activada por α7-nAChR: Una revisión narrativa

Introducción: los glucocorticoides (GC) han sido ampliamente utilizados en el tratamiento de patologías oculares debido a sus efectos antiinflamatorios y anti-angiogénicos. Se ha sugerido que el mecanismo de acción anti-angiogénico de los GC puede estar relacionado con la enzima fosfatidilinositol-3-cinasa (PI3K), la cual desempeña un papel crucial en la angiogénesis mediada por el receptor de acetilcolina nicotínico alfa 7 (α7-nAChR). La PI3K es una enzima lipoproteica heterodimérica compuesta por las subunidades; reguladora (p85) y catalítica (p110). Objetivo: esta revisión examina la evidencia de cómo los GC modulan la vía de señalización de PI3K activada por α7-nAChR en el proceso de angiogénesis in vitro. Metodología: se realizó una revisión bibliográfica utilizando los motores de búsqueda PubMed y Web of Science, relacionando los conceptos "endothelial cell", "α7-nAChR", "PI3K" y "glucocorticoid". Resultados: se seleccionaron 30 artículos que informaron sobre la expresión de α7-nAChR y PI3K en células endoteliales humanas. Además, del efecto de dexametasona sobre las subunidades de PI3K y Akt (proteína cinasa B) en modelos humano, murino y porcino. A partir de estos hallazgos, se propuso un mecanismo mediante el cual los GC ejercen su efecto anti-angiogénico a través de la modulación en la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR en células endoteliales humanas. Conclusión: los antecedentes evidencian que dexametasona, ejerce su mecanismo de acción anti-angiogénico mediante el incremento de la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR.

Introduction: glucocorticoids (GC) have been widely used in the treatment of ocular pathologies due to their anti-inflammatory and anti-angiogenic effects. It has been suggested that the anti-angiogenic mechanism of GC may be related to the enzyme phosphatidylinositol-3-kinase (PI3K), which plays a crucial role in angiogenesis mediated by the alpha 7 nicotinic acetylcholine receptor (α7-nAChR). PI3K is a heterodimeric lipoprotein enzyme composed of regulatory (p85) and catalytic (p110) subunits. Objective: this review examines the evidence of how the GC modulate the PI3K signaling pathway activated by α7-nAChR in the process of in vitro angiogenesis. Methodology: a literature search was conducted using the PubMed and Web of Science search engines, relating the concepts of "endothelial cell," "α7-nAChR," "PI3K," and "glucocorticoid." Results: thirty-two articles were selected that reported on the expression of α7-nAChR and PI3K in human endothelial cells. Furthermore, the effect of dexamethasone on PI3K and Akt (protein kinase B) subunits was documented in human, murine, and porcine models. Based on these findings, a mechanism was proposed whereby GC exert their anti-angiogenic effect through modulation of the expression of the inhibitory p85 subunit of PI3K activated by α7-nAChR in human endothelial cells. Conclusion: background evidence suggests that dexamethasone exerts its anti-angiogenic mechanism of action by increasing the expression of the α7-nAChR-activated PI3K inhibitory subunit p85

Detection of molecular affecting sensitivity to local glucocorticoid therapy in oral lichen planus through transcriptome sequencing / 北京大学学报(医学版)

Objective:To detect key genes of local glucocorticoid therapy in oral lichen planus(OLP)through transcriptome sequencing.Methods:The study prospectively enrolled 28 symptomatic patients who visitied Department of Oral Mucosa,Peking University Hospital of Stomatology from November 2019 to March 2023.Topical inunction of 0.1 g/L of dexamethasone was applied for 1 min,3 times daily for 4 weeks.The patients'signs and pain symptoms were recorded and they were classified as effective group and ineffective group according to the treatment outcome.Their mucosa samples were collected before treatment.After isolating total RNA,transcriptome sequencing was performed.The gene expression data obtained by sequencing were analyzed differently using the DESeq2 package in R software,and the Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was performed on the basis of the hypergeometric distribution algorithm to describe the biological function of differentially expressed genes(DEGs),accordingly detecting sensitivity related molecular affecting therapeutic effect of dexamethasone.Results:After 4 weeks treatment by topical dexamethasone,13 cases of the 28 OLP pa-tients responding well with the sign score reducing from 7.0(4.5,9.0)to 5.0(3.0,6.3),pain score decreasing from 5.0(2.0,5.5)to 2.0(0.0,3.5),oral health impact profile lessening from 5.0(3.5,9.0)to 1.0(0.0,5.0)significantly(P＜0.01)were classified as effective group and 15 cases with poor response to the drug were sorted as ineffective group.There were no significant differences of demographic and baseline levels of clinical features,especially disease severity between these two groups.A total of 499 DEGs including 274 upregulated and 225 downregulated genes were identified between ef-fective group and ineffective group.KEGG enrichment analysis showed that upregulated genes in effective group compared with ineffective group including CLDN8,CTNNA3,MYL2 and MYLPF were associated with leukocyte transendothelial migration,while downregulated genes were significantly enriched in tumor necrosis factor(TNF),interleukin-17(IL-17),nuclear factor kappa B(NF-κB)signaling pathways,and cortisol synthesis and secretory.Conclusion:High expressions of CLDN8,CTNNA3,MYL2 and MYLPF genes in patients with oral lichen planus have a good clinical response to topical dexamethasone,while patients with high expression genes of inflammation pathway such as TNF,IL-17,NF-κB and corti-sol synthesis and secretion received poor effect.

Clinical characteristics of 13 cases of organizing pneumonia secondary to invasive pulmonary aspergillosis / 重庆医学

Objective To analyze the clinical characteristics of organizing pneumonia secondary to inva-sive pulmonary aspergillosis.Methods A total of 13 patients with organizing pneumonia secondary to invasive pulmonary aspergillosis in the Department of Respiratory,the First Affiliated Hospital of Zhengzhou Univer-sity diagnosed by pathology from January 2019 to January 2021 were retrospectively included,and their clinical characteristics,laboratory examination,imaging characteristics,treatment and prognosis were comprehensively analyzed.Results Most cases of pulmonary aspergillosis occurred within 2-3 weeks of diagnosis,with coug-hing,expectoration,fever,and elevated C-reactive protein and erythrocyte sedimentation rate.Chest computed tomography showed patchy shadows around the original infection focus,mostly accompanied by consolidation,halo sign,bronchial inflation sign,and might be accompanied by cavity and pleural effusion;secondary multi lobed involvement of both lungs was observed,mostly with small patchy shadows,nodular shadows,and tree bud signs.After receiving glucocorticoid treatment,the symptoms were controlled within one week,and the glucocorticoid treatment course was mostly 3-6 months.Conclusion The clinical characteristics of organi-zing pneumonia secondary to invasive pulmonary aspergillosis are somewhat similar to those of cryptogenic or-ganizing pneumonia and have a better prognosis.

Relationship between serum endocan,DcR3 and airway inflammation in children with bronchial asthma / 国际检验医学杂志

Objective To investigate the relationship between serum endothelial cell specific 1(endocan),deception receptor 3(DcR3),airway inflammation and clinical efficacy in children with bronchial asthma.Methods A total of 171 children with bronchial asthma who were admitted to the hospital from June 2020 to June 2022 were selected as the observation group,and 80 healthy children who underwent physical examina-tion in the hospital during the same period were selected as the control group.The levels of serum endocan,DcR3 levels and exhaled nitric oxide(FeNO)in the two groups were compared,and the correlation between the serum endocan,DcR3 levels and FeNO level in the observation group was analyzed.The levels of serum endocan and DcR3 were compared after individualized glucocorticoid treatment.The related factors affecting the clinical efficacy of the children were analyzed by univariate and multivariate Logistic regression analysis.Results The levels of serum endocan,DcR3 and FeNO in the observation group were higher than those in the control group(P<0.05).There was positive correlation between the levels of serum endocan,DcR3 and Fe-NO in the observation group(r=0.569,0.398,P<0.05).After treatment,the levels of serum endocan,DcR3 and FeNO in the observation group were lower than those before treatment(P<0.05).After treatment,there were 140 cases of children in the effective group,and 31 cases of children in the ineffective group.Univariate a-nalysis showed that there were statistical differences between the effective group and the ineffective group in the severity of disease,allergy history,endocan,DcR3 and FeNO levels(P<0.05).Multivariate Logistic re-gression analysis showed that severity of disease,allergy history,elevated serum levels of endocan and DcR3 were all independent risk factors affecting the clinical efficacy of children(P<0.05).Conclusion The levels of serum endocan and DcR3 are significantly related with airway inflammation in children with bronchial asth-ma,and their abnormally high levels could affect the clinical efficacy of glucocorticoid treatment in children with bronchial asthma.

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.

Glucocorticoid hypersensitivity syndrome: A case report and review of literature / 中华内分泌代谢杂志

This article reports a patient with typical Cushing syndrome′s manifestations and extremely low plasma cortisol level, indicating glucocorticoid hypersensitivity syndrome. After treatment with the glucocorticoid receptor antagonist mifepristone, the patient′s Cushing symptoms were significantly relieved, and cortisol levels returned to normal. The aim of this report is to enhance clinical awareness among physicians regarding glucocorticoid hypersensitivity syndrome.

Acute viral bronchiolitis phenotype in response to glucocorticoid and bronchodilator treatment

Abstract Objective To analyze whether infants admitted to hospital with Acute Viral Bronchiolitis (AVB), who received glucocorticoids and bronchodilators, and who had an atopic phenotype, spent less time in hospital and/or less time on oxygen therapy when compared to those who did not have the phenotype. Method A cross-sectional, retrospective epidemiological study was developed with data from medical records of infants admitted to hospital due to AVB from 2012 to 2019 in a sentinel public hospital. It was verified that the frequency of prescription of glucocorticoids, bronchodilators and antibiotics. Length of stay and oxygen therapy duration were then compared in the group that used glucocorticoids and bronchodilators between those who had a personal or family history of atopy and those who did not. Subsequently, the length of hospital stay was compared among infants who received antibiotic therapy and those who did not. Results Fifty-eight infants were included. Of these, 62.1 % received an antibiotic, 100 % a bronchodilator and 98.3 % a glucocorticoid. When comparing infants without a family history of atopy, those who received antibiotics had a longer hospital stay (p = 0.01). Conclusion The presence of an atopic phenotype did not interfere with the length of stay and/or oxygen therapy duration of those who received bronchodilators and glucocorticoids. Increased length of stay of infants without a family history of atopy, who used antibiotics without evidence of bacterial co-infection, and the high frequency of prescription of non-recommended drugs call attention to stricter protocol implementation and professional training in AVB diagnosis and care.

Fucoxanthin alleviates glucocorticoid-induced osteoblast apoptosis by activating nuclear factor erythroid-2-related factor 2 / 中国组织工程研究

BACKGROUND:Osteoporosis has a high incidence,leading to fracture and other complications.However,existing drugs have great side effects and are difficult to meet the clinical application. OBJECTIVE:To explore the effect and potential mechanism of fucoxanthin on osteoporosis induced by glucocorticoid. METHODS:Primary rat osteoblasts were inoculated in 6-well plates.When the cell fusion reached 80%,the cells were divided into four groups:the control group was cultured alone for 24 hours,the glucocorticoid group was intervened with dexamethasone for 24 hours,the fucoxanthin group was intervened with fucoxanthin for 24 hours,and the glucocorticoid + fucoxanthin group was intervened with dexamethasone and fucoxanthin at the same time for 24 hours.After intervention,cell proliferation,apoptosis,intracellular reactive oxygen species level,and protein expression of apoptosis-related proteins,bone formation-related proteins,and nuclear factor erythroid-2-related factor 2 were detected. RESULTS AND CONCLUSION:Cell counting kit-8 results showed that the cell viability was decreased in the glucocorticoid group compared with the control group(P＜0.05)but increased in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group(P＜0.05).JC-1 mitochondrial membrane potential staining and flow cytometry assay showed that the percentage of apoptosis increased in the glucocorticoid group compared with the control group(P＜0.05)but decreased in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group(P＜0.05).Western blot assay showed that compared with the control group,the protein expression of BAX and cleaved poly(ADP-ribose)polymerase was elevated in the glucocorticoid group(P＜0.05),and the protein expression of BCL2,type Ⅰ collagen α1 peptide chain,alkaline phosphatase,osteocalcin,and RUNX2 was decreased in the glucocorticoid group(P＜0.05).Compared with the glucocorticoid group,the protein expression of BAX and cleaved poly(ADP-ribose)polymerase was decreased(P＜0.05),and the protein expression of BCL2,type Ⅰ collagen α1 peptide chain,alkaline phosphatase,osteocalcin,and RUNX2 was elevated(P＜0.05)in the glucocorticoid+fucoxanthin group.Fluorescent probe assay showed an increase in reactive oxygen species level in the glucocorticoid group compared with the control group(P＜0.05)and a decrease in reactive oxygen species level in the glucocorticoid+fucoxanthin group compared with the glucocorticoid group(P＜0.05).Immunofluorescence staining and western blot assay showed that the protein expression of nuclear factor erythroid-2-related factor 2 in the glucocorticoid group was decreased compared with that in the control group(P＜0.05);and the protein expression of nuclear factor erythroid-2-related factor 2 in the glucocorticoid+fucoxanthin group was elevated compared with that in the glucocorticoid group(P＜0.05).To conclude,fucoxanthin can improve glucocorticoid-induced osteoblast apoptosis and the expression of bone formation-related molecules by activating nuclear factor erythroid-2-related factor 2.

Active ingredients of Panax notoginseng regulate signaling pathways related to steroid-induced necrosis of the femoral head / 中国组织工程研究

BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.

Optimization of immunosuppressive regimen for kidney transplant recipients / 器官移植

With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.

Management of immunosuppressive drugs in HIV-positive solid organ transplant recipients / 器官移植

The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive soild organ transplant recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive soild organ transplant recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive soild organ transplant recipients was reviewed, aiming to provide reference for subsequent management of immunosuppression in HIV-positive soild organ transplant recipients.

The Mechanism of miR-124 in Depression / 生物化学与生物物理进展

Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

Analysis of the efficacy of glucocorticoid treatment in advanced thymoma / 中华胸心血管外科杂志

Objective:To explore the clinical efficacy and safety of moderate-dose glucocorticoid treatment in patients with advanced thymoma.Methods:A retrospective analysis was conducted on clinical data of 56 patients with thymoma who received glucocorticoid treatment at Beijing Tongren Hospital, Capital Medical University, from January 2018 to March 2023. Among them, there were 33 males and 23 females; aged from 28 to 72 years old, with a median age of(43.8±11.2)years old. There were 16 cases of type B1 thymoma, 23 cases of type B2, and 17 cases of type B3. There were 17 cases with myasthenia gravis and 1 case with pure red blood cell aplasia. All patients had received radiotherapy or chemotherapy. Patients received moderate-dose glucocorticoid treatment(50 mg/day), and tumor response was evaluated by CT scan after 2 weeks of treatment. The tumor treatment effect and adverse reactions were recorded.Results:Among the patients, 22 cases achieved partial remission, and 3 cases achieved complete remission, resulting in an overall objective response rate (ORR) of 44.6%. Among them, 23 patients had type B2 thymoma, with 17 achieving partial remission and 3 achieving complete remission, resulting in an ORR of 87.0%. Among the 16 patients with type B1 thymoma, 5 achieved partial remission. No efficacy was observed in 17 patients with type B3 thymoma. The follow-up period ranged from 2 to 26 months, and 2 patients experienced thymoma recurrence.Conclusion:Moderate-dose glucocorticoid treatment demonstrates effective and safe outcomes in advanced or invasive thymoma, particularly for the treatment of type B2 thymoma.

Research progress on pathological changes and molecular mechanism of trabecular meshwork in glucocorticoid-induced ocular hypertension / 国际眼科杂志(Guoji Yanke Zazhi)

Glucocorticoid-induced ocular hypertension(GIOH)is a condition characterized by elevated intraocular pressure caused by glucocorticoids. The long-term presence of GIOH may lead to optic nerve damage and visual field defects, eventually progressing to glucocorticoid-induced glaucoma(GIG), which can potentially cause blindness. Glucocorticoids primarily exert their biological effects by mediating glucocorticoid receptor(GR), while also involving factors such as transforming growth factor(TGF)-β, Wnt, and Rho in the formation of GIOH. In-depth exploration of the pathological changes and related molecular mechanisms of the trabecular meshwork in GIOH provides an important theoretical basis for understanding the pathogenesis and treatment of GIOH. Therefore, this article provides a review of the pathological changes and molecular mechanisms of the trabecular meshwork in GIOH, aiming to provide a theoretical basis for further research on the pathological mechanisms and treatment of GIOH.

Oral mucosal manifestations of Sweet’s syndrome: a case report and literature review / 口腔疾病防治

Objective@#To explore the oral mucosal manifestations of Sweet’s syndrome and provide a reference for its early detection and correct diagnosis.@*Methods@#The oral mucosal manifestations of a 60-year-old female patient with Sweet’s syndrome are described in detail, followed by a discussion of the related literature.@*Results@#The patient had skin erythema of both lower extremities, which was accompanied by oral mucosal ulceration and pain for 3 days. The patient presented with mild cutaneous lesions and diffuse large-scale erosion in the oral mucosa with obvious pain. During the onset of the disease, the patient was accompanied by fever with a temperature of 38.5°C. After visiting the Department of Stomatology, laboratory tests showed an increase in C-reactive protein (35.2 mg/L) and an accelerated erythrocyte sedimentation rate (77.00 mm/h). Scattered red plaques and mild tenderness were observed in the knees and lower limbs. Histopathological examination of the skin lesions revealed scattered infiltration of immature neutrophils across the entire dermis. The patient responded well to glucocorticoid therapy. According to the clinical signs and laboratory examination, combined with the lesion histopathological results, a diagnosis of Sweet’s syndrome was given. The patient was administered 1 mL compound Betamethasone injection only once intramuscularly. In the meantime, the patient was asked to gargle with compound chlorhexidine solution and topically apply recombinant bovine basic fibroblast growth factor solution to the damaged mucosa three times a day for 1 week. After 4 days of medication, the patient’s body temperature had returned to normal and the oral lesions were significantly reduced. After 2 weeks, the erythema in the leg and knee had almost all subsided, and the oral mucosal lesions had disappeared. The patient was followed up 6 months after treatment, with no recurrence of skin lesions. After 2 years of follow-up, the disease was stable with no recurrence. A review of the relevant literature shows that Sweet’s syndrome is a rare inflammatory reactive dermatosis with unknown etiology, which can be divided into three clinical types: specific, tumor-related, and drug-induced. The male/female prevalence ratio is 1:4. The salient clinical manifestations are abrupt onset of painful erythematous plaques or nodules most commonly involving the extremities, often accompanied by pyrexia, elevated neutrophil count, elevation of the erythrocyte sedimentation rate, and positive C-reactive protein. The use of glucocorticoids is the most common treatment for this disease, and most patients see a rapid improvement in skin lesions; however, some may experience infection or recurrence after withdrawal. Some patients with Sweet’s syndrome are accompanied by oral lesions, but cases of oral mucosal damage have been rarely reported, and this condition is easily misdiagnosed.@*Conclusion@#Oral mucosal lesions may be extraterritorial manifestations of Sweet’s syndrome, and the patient’s systemic condition should be comprehensively considered. Skin biopsy should be completed as soon as possible to make a clear diagnosis, so as not to delay the disease.

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 / 药学实践与服务

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.

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.

Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

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.