Effect of Yang-Warming and Kidney-Tonifying Prescription on Expression of Osteogenic and Angiogenic Factors and H-Type Vascular Markers in Steroid-Induced Avascular Necrosis of Femoral Head in Rabbits

Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whether its therapeutic mechanism is related to the expression of HIF-1α and VEGF (angiogenic factors), BMP2 and Osterix (osteogenic factor), CD31 (type H vascular marker) and MMP13 (bone destruction-related factor). Methods: Twenty-seven healthy male New Zealand white rabbits were divided into a normal group, model group, traditional Chinese medcine (TCM) group (clinical equivalent dose group of YKP), miR-130a inhibitor group and TCM + inhibitor group. The SANFH model was established by combining horse serum with methylprednisolone. After the model is successfully established, TCM group was given 6.44 g/kg·d YKP by gavage, and the miR-130a gene inhibitor group was intraperitoneally injected with 25 mg/kg miR-130a inhibitor, locked nucleic acid (LNA)-anti-miR-130a. TCM + inhibitor group was treated with YKP intragastrically and miR-130a inhibitor intraperitoneally. The rabbits in the normal group and the model group were intragastrically administered with normal saline 10 ml/d. Once a day for 4 weeks. The avascular necrosis was detected by HE staining. The contents of HIF-1α, VEGF, BMP2 and Osterix in rabbit tissues were detected by qRT-PCR kit, and the expression of CD31 and MMP13 was detected by immunofluorescence staining. Results: In the normal group, the surface of the cartilage layer of the femoral head was smooth, the bone trabeculae were intact and densely arranged, the cells of each layer were neatly arranged, the morphology of the bone cells, the chondrocytes and the adipocytes were normal. In the model group, cartilage surfaces of the femoral head showed exfoliative cracks. The bone trabecular structure was loose and incomplete, chondrocytes, osteoblasts and bone marrow cells were significantly reduced, and the number of empty bone traps was significantly increased. In the TCM-treated group, more chondrocytes, thicker cartilage layer, and more regular bone trabeculae were detected as compared to model rabbits. In contrast, the cartilage layer was thinner, the destruction and fracture of bone trabeculae was more serious, chondrocytes and osteocytes were decreased as compared to model group. The expression of HIF-1α, VEGF, BMP2, and Osterix in the model group decreased significantly as compared to the normal group (P Conclusion: YKP can regulate the expression of angiogenic-related factors (VEGF and HIF-α), osteogenic-related factors (BMP2 and Osterix), and H-type vascular marker CD31, resulting in increased expressions of VEGF, HIF-α, BMP2, and Osterix, which promote intra-femoral head revascularization. Meanwhile, YKP decreased the expression of bone-destruction-related factor MMP13, thus enhancing the ability of bone tissue to repair itself. Regulation of these molecules’ expression may be one of the mechanisms of YKP in the treatment of hormonal femoral head necrosis.

Steroid-induced psychosis related to pituitary adenoma status post trans-sphenoid excision and a history of psychiatric illness:A case

BACKGROUND Steroid-induced psychosis is a common adverse effect of steroid exposure.Reported cases were mostly related to rheumatologic disease.Despite its high incidence,there is only one case reported related to perioperative steroid replacement for pituitary adenoma surgery.This manuscript presents the second case of such and compared the two with the latest literature review of steroidinduced psychosis.CASE SUMMARY This is a case of an adult male with a chief complaint of auditory hallucinations and was referred by Neurosurgery to Psychiatry Out-patient department.He was diagnosed with pituitary adenoma who underwent trans-sphenoid excision of the mass from which steroid exposure led to steroid-induced psychosis.Also,patient had a history of psychiatric illness of severe depressive episode.At the out-patient department,patient was started on antipsychotic,Risperidone,which led to eventual improvement of his symptoms.CONCLUSION The two cases of pituitary adenoma surgery with steroid-induced psychosis had almost similar clinical profile with the latest literature review of steroid-induced psychosis.However,the present case highlights the association of psychiatric illness in predisposing an individual in developing it.Also,this manuscript emphasizes that early recognition of steroid-induced psychosis leads to better prognosis.Multispecialty treatment is vital in the holistic management of the patient with timely referral and close coordination.

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.

Gubi Tongxiao granules regulate vasculization and apoptosis to intervene steroid-induced femoral head necrosis in rabbits

Objective:To investigate the effect of Gubi Tongxiao granules on vascular formation and cell apoptosis in the process of glucocorticoid-induced femoral head necrosis.Methods:Thirty experimental New Zealand rabbits were randomly divided into groups.Except the control group,the animal model of steroid-induced femoral head necrosis was established by lipopolysaccharide combined with glucocorticoids.After successful modeling,the experimental group was given Gubi Tongxiao granules intragastric treatment,the model and control group were given the same amount of normal saline intragastric treatment,once a day,for 8 weeks,the experimental animals were sacrificed,the bilateral femoral head of each group was taken out for hematoxylin-eosin staining,and protein CD34,CYR61 and VEGF were immunohistochemical staining localization.TUNEL staining was used to observe the apoptosis of femoral head cells.The expression levels of apoptosis proteins Bax and Bcl-2 were detected by WB.The expression of VEGF eNOs Bax and Bcl-2 genes was analyzed by RT-qPCR.Results:Gubi Tongxiao granules reduced the number of hollow bone lacunae and apoptotic positive cells(P<0.01),and up-regulated the expressions of CD34,CYR61 and VEGF in femoral head tissue.Compared with control group,the expression of pro-apoptotic protein Bax increased and the expression of anti-apoptotic protein Bcl-2,VEGF and eNOs mRAN decreased significantly in the model group(P<0.01),the opposite results were obtained in the experimental group after Gubi Tongxiao granule intervention(P<0.05).Conclusion:Gubi Tongxiao granules can improve the expression of angiogenic genes and regulate apoptosis-related proteins in the bone tissue of rabbit model with steroid-induced necrosis of femoral head,promote angiogenic differentiation and inhibit apoptosis,and thus achieve the effect of treating steroid-induced necrosis of femoral head.

Successful Management of a Complicated Ulcer Caused by Autoimmune Vasculitis, with Sildenafil Citrate in a Patient with Primary Antiphospholipid Syndrome and Transient Steroid-Induced Diabetes Mellitus: A Case Report and Literature Review

Antiphospholipid syndrome (APS) is a prothrombotic condition that can affect both the venous circulation and the arterial system. The deep veins of the lower extremities and cerebral blood flow are the most common sites of venous and arterial thrombosis, respectively. Skin ulceration and gangrene may be associated with an active vasculitis in patients with APS. These kinds of ulcers are considered intractable because healing is difficult to achieve. Using steroids as immunesuppressant therapy is still a basic part of managing APS and vasculitis. Nevertheless, in the presence of steroid-induced diabetes mellitus, the priority is to achieve faster wound healing, because of the potential complications that can develop due to metabolic dysfunction and augmented vulnerability to infection. Until recently, there were few reports demonstrating the benefits of the use of adjuvant phosphodiesterase-5 inhibitors like sildenafil citrate in different clinical entities with courses like Raynaud’s phenomenon, scleroderma, and resistance to vasodilator therapy. We present the first report demonstrating the additional benefit of sildenafil citrate for the integration of grafts in a patient with steroid-induced diabetes and APS who had ulcers due to vasculitis resistant to the usual vasodilator therapy.

Interactions between diabetes and COVID-19:A narrative review

Diabetes,whether due to pancreatic beta cells insufficiency or peripheral resistance to insulin,has been suggested as a risk factor of developing severe acute respiratory disease coronavirus-2(SARS-CoV-2)infections.Indeed,diabetes has been associated with a higher risk of infections and higher risk of developing severe forms of coronavirus disease 2019(COVID-19)related pneumonia.Diabetic patients often present associated comorbidities such as obesity,hypertension and cardiovascular diseases,and complications of diabetes,including chronic kidney disease,vasculopathy and relative immune dysfunction,all of which make them more susceptible to infectious complications.Moreover,they often present lowgrade inflammation with increased circulating interleukin levels,endothelial susceptibility to inflammation and dysfunction,and finally,hyperglycemia,which increases this risk.Additionally,corticosteroids,which count among the few medications which showed benefit on survival and mechanical ventilation requirement in COVID-19 pneumonia in large randomized controlled trials,are associated to new onsets of diabetes,and metabolic disorders in patients with previous history of diabetes.Finally,SARS-CoV-2 via the alternate effects of the renin-angiotensin system,mediated by the angiotensin-converting-enzyme 2,was also associated with insulin resistance in key tissues involved in glucose homeostasis,such as liver,skeletal muscles,and adipose tissue;and also,with impaired insulin secretion by pancreaticβ-cells.In this work,we reviewed all elements which may help understand how diabetes affects patients with COVID-19,how treatments affect outcomes in patients with COVID-19,how they may cause new onsets of diabetes,and finally review how SARS-CoV-2 may inherently be a risk factor of developing diabetes,through immune-mediated diabetogenic mechanisms.

Expression profile analysis to identify potential gene changes induced by dexamethasone in the trabecular meshwork

AIM:To investigate potential gene changes in trabecular meshwork(TM)induced by dexamethasone(DEX)in steroidinduced glaucoma(SIG).METHODS:The expression data of 24 cases from a public functional genomics data were sorted to identify the mechanisms of action of DEX on the TM.The relationships of the differentially expressed genes(DEGs)were enriched using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.In addition,the hub genes were screened by the Search Tool for the Retrieval of Interacting Genes Database(STRING)and Cytoscape tools.Finally,human TM cells(HTMCs)were treated with DEX to preliminarily explore the function of hub genes.RESULTS:Totally 47 DEGs,including 21 downregulated and 26 upregulated genes were identified.The primary enriched results of the DEGs consisted of inflammatory response,extracellular matrix(ECM),negative regulation of cell proliferation,TNF signalling pathway and the regulation of tr yptophan channels by inflammator y mediators.Subsequently,pro-melanin-enriched hormone(PMCH)and Bradykinin B1 receptor(BDKRB1)were screened as hub genes.It is verified in GSE37474 data set.Western blot and quantitative real-time polymerase chain reaction(q PCR)results showed that protein and RNA expression levels of BDKRB1 were significantly decreased after DEX treatment,while PMCH was not significantly changed.CONCLUSION:BDKRB1 may be a key gene involved in SIG onset,providing a suitable therapeutic target for improving the prognosis of SIG patients.

Study on the Effect of Youguiyin(右归饮) on Regulating Gene Expression Profile of the Rats with Femoral Head Necrosis Induced by Steroid

Objective： To observe the regulation of Youguiyin （YGY, 右归钦） on the gene expression profile of the rat with steroid-induced femoral head necrosis （sFHN）, for the sake of investigating its molecular mechanism of sFHN prevention and treatment. Methods： All the 30 rats were randomly divided into three groups, the normal control group （A）, the model control group （B）, and the YGY treated group （C）, 10 in each group. After rats in Groups B and C were being made into FHN models with steroid injection, they received a daily intragastdc administration of saline and YGY respectively in equal volume for a total of 6 weeks, while to the unmodeled normal rats in Group A, saline was administered instead. The rats were sacrificed at the terminal of administration; their mRNA from femoral head tissue was extracted and prepared to cDNA probe through inverse transcription for detecting gene expression profile by microarray, outcomes of which was passing fluorescence quantitative PCR verification, and the differential expressed genes were analyzed adopting gene ontology （GO） method. Results： Compared with Group A, the numbers of differential genes found in Groups B and C were 190 and 92, respectively, but the changing trend in the two groups was opposite, mainly manifested as down-regulating in Group B/Group A （GB/GA） and up-regulating in Group C/Group B （GC/GB）. The analysis showed that these differential genes were mainly assigned to cell apoptosis, signal transduction, metabolism, cell proliferation and differentiation, cell cycle, blood coagulation, antioxidant activity, etc. Conclusions： sFHN was regulated by various genes; the regulation of YGY on expressions of these genes and the intra]extra-cellular signaling processes was possibly the molecular mechanism of YGY for preventing/treating sFHN. This study gave an explanation to the effectiveness of Chinese medicine in preventing/treating FHN from aspects of gene expression and enriched the Chinese medicine theory of ＂Kidney （Shen） governing bones＂.

Glaucoma secondary to systemic lupus erythematosus

Background Glaucoma secondary to systemic lupus erythematosus （SLE - an uncommon but serious complication that threatens vision and therefore cannot be neglected. A few cases of second, y glaucoma resulting from lupus-induced or iatrogenic ocular impairments have been reported in association with SLE. However, a systematic analysis of the diagnosis and treatment of glaucoma secondary to SLE has not been reported in the literature. The aim of this study is to further investigate the relationship between glaucoma and SLE. Methods In this study, we reviewed nine eyes of five patients diagnosed with secondary glaucoma associated with SLE, including one case of neovascular glaucoma and four cases of steroid-induced glaucoma. Results Neovascular glaucoma was successfully treated by Ahmed glaucoma valve implantation surgery with adjunctive ranibizumab intravitreal injection, followed by panretinal photocoagulation （PRP）. The steroid-induced glaucoma in eight eyes of four cases were controlled by trabeculectomy along with antiproliferative agents. Conclusion Regular follow-up ocular examinations should be conducted to ensure early diagnosis and treatment of secondary glaucoma in SLE patients to improve the prognosis of vision.

Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma

Background:Heliotropium indicum is used as a traditional remedy for hypertension in Ghana.The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H.indicum to manage experimentally-induced glaucoma.Methods:The percentage change in intraocular pressure(IOP),after inducing acute glaucoma(15 mLkg^(−1) of 5%dextrose,i.v.),in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract(HIE)(30–300 mgkg^(−1)),acetazolamide(5 mgkg^(−1)),and normal saline(10 mLkg^(−1))per os were measured.IOPs were also monitored in chronic glaucoma in rabbits(induced by 1%prednisolone acetate drops,12 hourly for 21 days)after treatments with the same doses of HIE,acetazolamide,and normal saline for 2 weeks.The anti-oxidant property of the extract was assessed by assaying for glutathione levels in the aqueous humour.Glutamate concentration in the vitreous humour was also determined using ELISA technique.Histopathological assessment of the ciliary bodies was made.Results:The extract significantly reduced intraocular pressure(p≤0.05–0.001)in acute and chronic glaucoma,preserved glutathione levels and glutamate concentration(p≤0.01–0.001).Histological assessment of the ciliary body showed a decrease in inflammatory infiltration in the extract and acetazolamide-treated group compared with the normal saline-treated group.Conclusion:The aqueous whole plant extract of Heliotropium indicum has ocular hypotensive,anti-oxidant and possible neuro-protective effects,which therefore underscore its plausible utility as an anti-glaucoma drug with further investigation.