Influence of sexual hormones on Chagas disease / Influencia de las hormonas sexuales en la enfermedad de Chagas

Abstract Objective: Analyze sex hormone's influence during Chagas disease. Methods: Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups' data. P-values < 0.05 were considered statistically significant. Results: Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Conclusions: Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´ infuence upon this infection to contribute with the handling of Chagas´ disease.

Resumen Objetivo: Analizar la influencia de las hormonas durante la enfermedad de Chagas. Métodos: Se separaron grupos de ratones macho y hembras BALB/c, todos infectados con T. cruzi (cepa NINOA), 4 grupos experimentales de machos (Sham, orquidectamizados, orquidectimezados y suplementados con estradiol, orquidectamizaos y suplementados con testosterona). 4 grupos experimentales de hembras (oforectomizadas, oforectomizadas y suplementadas con estradiol, oforectomizadas y suplementadas con testosterona y sham), and y dos grupos control para cada sexo (sin infección e infectados intraperitonealmente con T. cruzi (cepa NINOA). Los datos clínicos fueron registrados diariamente, la parasitemia fue evaluada durante toda la infección utilizando una cámara de Neubauer y el análisis histopatológico del corazón fue realizada con la técnica de inclusión en parafina. Para el análisis de las curvas de parasitemia y el área bajo la curva, se realizó una prueba de ANOVA de dos vías, p < 0.05 fueron considerados estadísticamente diferentes. Resultados: Las mayores tasas de mortalidad, cardiomegalia, hepatomegalia y mayor infiltrado inflamatorio, se encontró en los ratones con una mayor concentración de testosterona. En contraste los ratones con mayor concentración de estradiol presentaron paresia, postración edema y necrosis. Conclusiones: Nuestros resultados ponen en manifiesto que la testosterona incrementa la severidad del curso de la enfermedad de Chagas, mientras que el estradiol tuvo el efecto opuesto. Este trabajo mejora el entendimiento del rol que juegan las hormonas sexuales en esta infección para contribuir en un mejor manejo de la enfermedad de Chagas.

Gender affirming hormone therapy and transgender women fertility: Histologic predictors of germ cell presence

Abstract Objective: Evaluate histological changes in testicular parameters after hormone treatment in transgender women. Methods: Cross-section study with patients who underwent gonadectomy at Hospital de Clínicas de Porto Alegre from 2011 to 2019. Hormone treatment type, route of administration, age at initiation and duration were recorded. Atrophy parameters were observed: testicular volume, tubular diameter, basal membrane length, presence of spermatogonia and spermatids (diploid and haploid spermatozoid precursors). Results: Eighty-six patients were included. Duration of hormone treatment is associated with testicular atrophy and spermatogenesis arrest. Other characteristics of hormone treatment such as age of initiation, route of administration and type of treatment were not associated with testicular histological changes. Testicular volume may predict spermatogenesis arrest. Basal membrane length and tubular diameter ratio is an interesting predictor of germ cell presence. Conclusion: Cross-sex hormone treatment affects testicular germ cell presence. Basal membrane length and tubular diameter ratio reduces inter variability of measurements and better exemplify how atrophic seminiferous tubules are. Fertility preservation should be addressed by healthcare providers in order to recognize gender affirming treatment impact on transgender health.

Knee Laxities Changes with Sex-steroids throughout the Menstrual Cycle Phases in Athlete and Non-athlete Females / Mudanças na flacidez do joelho com esteroides sexuais durante as fases do ciclo menstrual em mulheres atletas e não atletas

Abstract Objective: Our study investigated changes of knee laxities in athletes and non-athletes females and relationship between knee laxity and sex-steroid at menstrual cycle phases. Methods: Forty six healthy females, twenty four athletes and twenty two non-athletes not on hormone contraceptive pills, had no previous knee injuries and with regular menstrual cycles for 3 consecutive months, participated in the study. Medial and lateral knee laxities were determined by varus-valgus tests at follicular, ovulatory and luteal phases. Serum level of relaxin, estrogen, progesterone and testosterone were determined by ELISA and radioimmunoassay. Results: Knee laxities in athletes and non-athletes at 0° and 20° flexion were the highest in luteal phase with non-athletes possess greater laxity than athletes. Positive correlation between progesterone and relaxin levels with knee laxities were observed. Meanwhile, the levels of both hormones were highest in the luteal phase. Conclusion: Increased medial and lateral knee laxities in athletes and non-athletes associated with high serum progesterone and relaxin levels in luteal phase may contribute toward increased risk of non-contact knee injury. However, lower knee laxity in athletes than non-athletes suggest that exercise could be a protective factor.

Resumo Objetivo: Nosso estudo investigou alterações na lassidão do joelho em atletas e não atletas do sexo feminino e a relação entre a lassidão do joelho e esteroides sexuais nas fases do ciclo menstrual. Métodos: Quarenta e seis mulheres saudáveis, vinte e quatro atletas e vinte e duas não atletas, sem uso de pílulas anticoncepcionais hormonais, sem lesões anteriores no joelho e com ciclos menstruais regulares por 3 meses consecutivos, participaram do estudo. A lassidão medial e lateral do joelho foi determinada por testes de varo-valgo nas fases folicular, ovulatória e lútea. Os níveis séricos de relaxina, estrógeno, progesterona e testosterona foram determinados por ensaio imunoenzi mático (ELISA) e radioimunoensaio. Resultados: A lassidão do joelho em atletas e não atletas em 0° e 20° de flexão foi maior na fase lútea; as não atletas apresentavam maior lassidão do que as atletas. Houve uma correlação positiva entre os níveis de progesterona e relaxina e a lassidão do joelho. Além disso, os níveis desses dois hormônios foram maiores na fase lútea. Conclusão: O aumento da lassidão medial e lateral do joelho em atletas e não atletas, associado a altos níveis séricos de progesterona e relaxina na fase lútea, pode contribuir para o aumento do risco de lesão sem contato no joelho. No entanto, a menor lassidão do joelho em atletas do que em não atletas sugere que o exercício pode ser um fator protetor.

Evaluation of the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

Research Progress of Monogenic Mutation in the Pathogenesis of Steroid-Resistant Nephrotic Syndrome / 罕见病研究

Steroid-resistant nephrotic syndrome (SRNS) is the second cause of chronic kidney disease in children. The SRNS has high risk of rapid progression to end-stage renal disease. With the advancement of high-throughput sequencing technology, more than 70 monogenic mutation having the Mendelian inheritance patterns are identified to be associated with SRNS. Most of these genes are involved in podocyte function. Accurate diagnosis of monogenic mutation in SRNS patients helps with guiding clinical treatment protocols and genetic counseling, avoiding the excessive use of steroids/immunosuppressive therapy, and opening up possibilities for targeted therapies in SRNS patients. In this article, our research team summarizes and generalizes the molecular mechanisms, genetic testing, and specific treatment for the major types of monogenic mutations associated with SRNS.

Frecuencia de mutaciones encontradas en niños con enfermedad renal crónica por síndrome nefrótico cortico-resistente / Frequency of mutations found in children with chronic kidney disease due to steroid-resistant nephrotic syndrome

RESUMEN La enfermedad renal crónica en niños puede tener como etiología un grupo cuya causa genética, incluye las anomalías congénitas del riñón y las vías urinarias y las nefropatías hereditarias. Objetivo: Describir la frecuencia de mutaciones en niños con síndrome nefrótico corticoresistente (SNRE). Material y métodos: Estudio multicéntrico, tipo serie de casos, realizado en niños con SNRE, mediante el resultado de secuenciamiento directo de los genes; NPHS1, NPHS2, NPHP1 y WT1. Resultados: Se enrolaron 33 pacientes pediátricos con enfermedad renal crónica, 45,5% mujeres, edad promedio 13±7 años, 78,8% de raza mestiza, 24,2% consanguíneos, 60,6% se encontraban en hemodiálisis, 72,7% presentaban síndrome nefrótico cortico resistente y de ellos 8/24 (33,3%) presentó al menos una mutación en los genes; WT1, NPHS1, NPHP1y NPHS2 siendo la frecuencia de estas mutaciones de 37,5% (3/8), 25% (2/8), 25% (2/8) y 12,5% (1/8), respectivamente. Conclusiones: El 33,3% de los pacientes pediátricos con enfermedad renal crónica con síndrome nefrótico corticoresistente (SNRE) presentaron mutaciones, la más frecuente fue en el gen WT1.

SUMMARY Chronic kidney disease in children may be caused by a group of genetic abnormalities of the kidney, urinary tract and hereditary nephropathies. Objective: To report the frequency of mutations in children with steroid-resistant nephrotic syndrome (SRNS). Methods: A multicentric case series among children with SRNS identified through direct sequencing of NPHS1, NPHS2, NPHP1 and WT1 genes. Results: 33 children were enrolled; 45.5% were females; mean age was 13±7 years; 78.8% were mestizo: 24.2% consanguineous; 60.6% were receiving dialysis: 72.7% had SRNS and 8/24 (33.3%) of them presented at least one mutation to WT1, NPHS1, NPHP1 and NPHS2 genes. Corresponding values for these mutations were 37.5% (3/8), 25% (2/8), 25% (2/8) and 12.5% (1/8), respectively. Conclusions: 33% of pediatric patients with SRNS presented gene mutations, the most frequent of these mutations was WT1.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study / Desfechos de crianças com síndrome nefrótica idiopática córtico-resistente: um estudo observacional de centro único

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

Role of methylprednisolone in the prevention of seroma formation after mastectomy: A randomized controlled trial

Background: Seroma formation after mastectomy with axillary dissection is a major source of morbidity and results in a significant delay in starting the adjuvant treatment. Many different strategies, including the usage of steroids, have been tried to reduce the incidence of seroma with varying outcomes. This study aimed to assess the effect of a single dose of intracavitary methylprednisolone (MP) on seroma formation in patients undergoing total mastectomy with axillary lymph node dissection (ALND). Methods: A randomized controlled trial was conducted at our institute, from January 2018 till June 2019. In the intervention group of 36 patients, 80 mg of MP solution was injected into the wound on post operative day 1. The drain was clamped for 8 hours and then released. In the control group of 36 patients, saline was administered and the drain output was compared between the groups. Results: The mean drain volume in the intervention group was 409.08 mL and in the control group it was 566.97 mL (P < 0.005). The mean drain removal time was 7.86 days and 10.33 days in the intervention and control group, respectively (P < 0.0004). Conclusion: A single dose of intracavitary MP significantly reduced seroma formation and facilitated early removal of drain in patients undergoing total mastectomy with ALND.

Unique Cytomegalovirus Tongue Ulcer in an Older Adult Patient with Prolonged Systemic Steroid Treatment

Introduction: Cytomegalovirus (CMV) is a member of the Herpesviridae family that infects humans. It infects approximately 90% of adults. It is an opportunistic pathogen, common among immunosuppressed patients and can affect multiple organs. To date, there has been only one reported case of a CMV-related tongue ulcer that occurred during steroid treatment. Case Presentation: We report a case of CMV tongue ulcer in an elder, immunodeficient patient under prolonged steroid treatment. Management and Prognosis: A 67-year-old man under chronic steroidal treatment due to severe chronic obstructive pulmonary disease (COPD), with chronic ischemic heart disease (CIHD) and poorly treated diabetes mellitus (DM) was hospitalized in Soroka university medical center. He suffered from an ulcerative wound about 10 mm in its greater diameter with raised margins on the left lateral tongue. Daktarin Oral Gel treatment showed no improvement. On histopathological examination, a diagnosis of CMV-related tongue ulcer was given. Conclusion: To the best of our knowledge, this is the most detailed case report of CMV tongue ulcer due to prolonged steroid treatment. An early diagnosis of CMV infection in patients with oral lesions is crucial because CMV infection can increase immunosuppression, and is associated with opportunistic infections.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Traditional Chinese Medicine Regulates Wnt/β-catenin Signaling Pathway to Treat Steroid-induced Femoral Head Necrosis： A Review / 中国实验方剂学杂志

Steroid-induced necrosis of the femoral head （SNOFH） is a common orthopedic disease，which is difficult to cure and has poor clinical prognosis. The number of SNOFH patients in China is still increasing year by year，which seriously threatens human health. Long-term non-standard or short-term extensive use of hormone （GC） is an important reason for the occurrence of this disease. At present，SNOFH is mostly treated by surgical methods such as hip replacement，which has limitations of great harm to patients and high cost. In recent years，with the continuous deepening and innovation of traditional Chinese medicine（TCM） research，the use of TCM to treat SNOFH has been widely used in clinical practice. The main TCM pathogenesis of SNOFH is kidney deficiency and blood stasis. Therefore，TCM monomer and compound compound of tonifying kidney and promoting blood circulation are used to treat SNOFH. And TCM has obvious therapeutic effect，small side effects，less cost and other advantages. Glycoprotein/beta chain protein secretion （Wnt/beta- catenin） signaling pathway as a classic signaling pathway is closely related to the bone，between its by promoting bone marrow mesenchymal stem cell update，enhance the activity of osteoblast and suppress the apoptosis，which adjust the metabolic balance of bone tissue，increase bone density，will play an important role in the process of bone formation. In recent years，the use of TCM monomers and compounds to regulate Wnt/β-catenin signaling pathway to accelerate bone marrow mesenchymal stem cells，promote their transformation into osteoblasts，and maintain bone metabolic balance mechanism to treat SNOFH has become a new research hotspot. This article reviews the research progress of TCM in the prevention and treatment of SNOFH by regulating Wnt/β-catenin signaling pathway，in order to provide reference for the application of TCM in the treatment of SNOFH.

Biosynthesis of steroidal intermediates using Mycobacteria: a review / 生物工程学报

Steroids are a class of medicines with important physiological and pharmacological effects. In pharmaceutical industry, steroidal intermediates are mainly prepared through Mycobacteria transformation, and then modified chemically or enzymatically into advanced steroidal compounds. Compared with the "diosgenin-dienolone" route, Mycobacteria transformation has the advantages of abundant raw materials, cost-effective, short reaction route, high yield and environmental friendliness. Based on genomics and metabolomics, the key enzymes in the phytosterol degradation pathway of Mycobacteria and their catalytic mechanisms are further revealed, which makes it possible for Mycobacteria to be used as chassis cells. This review summarizes the progress in the discovery of steroid-converting enzymes from different species, the modification of Mycobacteria genes and the overexpression of heterologous genes, and the optimization and modification of Mycobacteria as chassis cells.

Optic neuritis in Guillain-Barré syndrome: a case report and literature review / 中华神经科杂志

Objective:To summarize the clinical characteristics of patients with Guillain-Barré syndrome (GBS) complicated with optic neuritis (ON).Methods:The clinical data of a patient with GBS complicated with ON, who admitted to the Department of Neurology, the First Hospital of Shanxi Medical University in December 2021, were collected, including demographic characteristics, clinical symptoms and signs, laboratory and electrophysiological data, and results of fundus color films. The patients with GBS complicated with ON reported in the literature were also reviewed.Results:A 40-year-old female patient with GBS was diagnosed by the results of electromyography and cerebrospinal fluid tests combining with the history and signs, who was treated with intravenous immunoglobulin on the 3rd day after onset. On the 8th day, her muscle strength improved significantly. However, on the 12th day, the visual field darkened, and on the 19th day, the vision decreased significantly (oculus dexter visual acuity 0.2, oculus sinister visual acuity 0.1 +1) with bilateral papilloedema, a relative afferent pupillary defect and delayed P100 response of the visual evoked potential. Obvious abnormality was not noted in optic nerve magnetic resonance imaging. Thus ON was diagnosed and treated with pulse methylprednisolone therapy. After 8 days of treatment, the visual acuity was completely recovered and there was no abnormality in the ocular fundus. A total of 28 cases of GBS complicated with ON (including the present patient) were reported in the literature. The age of onset was mostly 20-60 years, and there was no gender preference. Mycoplasma pneumoniae was the most common premorbid pathogen and was identified in 7 of the 10 cases in which the causative agent was described. ON usually involved both sides, and 21 of 28 patients had bilateral optic nerves involved. GBS preceded ON or both occurred simultaneously in the majority of patients; GBS preceded ON in 14 of 28 patients, and both occurred simultaneously in 10 of 28 patients. All patients responded well to immunotherapy, and vision was completely recovered in 20 patients. Conclusions:GBS complicated with ON is rare. Attention should be paid to the loss of vision in patients with GBS. Relevant examinations should be completed as soon as possible and immunotherapy should be given.

Exploring the intervention mechanism of Ginkgo biloba for steroid-induced necrosis of the femoral head based on network pharmacology / 中国临床药理学与治疗学

AIM: To explore the mechanism of Ginkgo biloba in the treatment of steroid-induced osteonecrosis of the femoral head based on network pharmacology. METHODS: The active ingredients and targets of Ginkgo biloba were predicted by the TCMSP, ADME, and PharmMapper databases. The disease targets related to steroid-induced osteonecrosis of the femoral head were searched by the GeneCards and OMIM databases. Cytoscape 3.6.1 was used to construct a protein-protein interaction network. The core target analysis, modular analysis, GO enrichment analysis, and KEGG pathway analysis of the targets of Ginkgo biloba in the intervention of steroid-induced osteonecrosis of the femoral head were performed by the STRING database. RESULTS: In this study, a total of 16 active ingredients of Ginkgo biloba and 547 targets were screened, of which 133 targets were related to steroid-induced femoral head necrosis. By PPI network topology analysis, TP53, AKT1, IL6, VEGFA, MAPK1, JUN, MAPK8, EGFR, EGF, and MYC were identified as the core targets. GO modularization analysis showed that these core targets were mainly related to apoptosis and angiogenesis. GO enrichment analysis was used to analyze the biological processes, cellular localization, and molecular functions of the core targets. KEGG enrichment analysis showed that the targets were mainly involved in molecular signaling pathways, among which the PI3K/AKT signaling pathway was the most relevant. CONCLUSION: Ginkgo biloba can inhibit steroid-induced osteonecrosis of the femoral head through multiple components, targets, and pathways, which provides the theoretical basis and reference for subsequent cell and animal experiments.

Steroid and triterpenoid saponins from the rhizomes of Paris polyphylla var. stenophylla / 中国天然药物

Five new saponins, including three steroid saponins, paristenoids A-C (1-3), and two triterpenoid saponins, paristenoids D-E (4-5), along with four known ones (6-9) were isolated from the rhizomes of Paris polyphylla var. stenophylla. The structures of the isolated compounds were identified mainly by detailed spectroscopic analysis, including extensive 1D and 2D NMR, MS, as well as chemical methods. Compound 3 is a new cyclocholestanol-type steroidal saponin with a rare 6/6/6/5/5 fused-rings cholestanol skeleton, and this skeleton has been first found from the genus Paris. The cytotoxicities of the isolated compounds against three human three glioma cell lines (U87MG, U251MG and SHG44) were evaluated, and compound 7 displayed certain inhibitory effect with IC50 values of 15.22 ± 1.73, 18.87 ± 1.81 and 17.64 ± 1.69 μmol·L-1, respectively.

Identification of a new C-23 metabolite in sterol degradation of Mycobacterium neoaurum HGMS2 and analysis of its metabolic pathways / 生物工程学报

Mycobacterium neoaurum has the ability to produce steroidal intermediates known as 22-hydroxy-23, 24-bisnorchol-4-en-3-one (BA) upon the knockout of the genes for either the hydroxyacyl-CoA dehydrogenase (Hsd4A) or acyl-CoA thiolase (FadA5). In a previous study, we discovered a novel metabolite in the fermentation products when the fadA5 gene was deleted. This research aims to elucidate the metabolic pathway of this metabolite through structural identification, homologous sequence analysis of the fadA5 gene, phylogenetic tree analysis of M. neoaurum HGMS2, and gene knockout. Our findings revealed that the metabolite is a C23 metabolic intermediate, named 24-norchol-4-ene-3, 22-dione (designated as 3-OPD). It is formed when a thioesterase (TE) catalyzes the formation of a β-ketonic acid by removing CoA from the side chain of 3, 22-dioxo-25, 26-bisnorchol-4-ene-24-oyl CoA (22-O-BNC-CoA), followed by spontaneously undergoing decarboxylation. These results have the potential to contribute to the development of novel steroid intermediates.

A Case of Postoperative Pyoderma Gangrenosum after Mitral Valve Replacement / 日本心臓血管外科学会雑誌

A 47-year-old man had severe mitral regurgitation after severe skin eruption, so mitral valve replacement was electively performed 8 months later. A median sternal wound opened spontaneously and had purulent exudate on the 5th postoperative day (5 POD). We had suspicion of bacterial mediastinitis, so we drained the anterior mediastinum and tried antibiotic treatment. However, the microbiological stains and culture were negative, and adipose tissue was extremely melted with pustules around the wound. Considering other diseases without infection, we consulted to a dermatologist and tried highdose steroid therapy as pyoderma gangrenosum (PG) appeared on the 8 POD. Meanwhile, the sternum was left open and apllied a negative pressure dressing applied with Negative Pressure Wound Therapy (NPWT). The wound responded remarkably to steroid therapy, so we closed the sternum on the 10 POD, and sutured the sternal wound on the 19 POD. We tapered off steroids after the suture. PG can be caused by the trauma of surgery, so we have to make a decision on whether to use high dose steroid therapy in the postoperative period. We report this case as one of the differential diseases that the surgeons must know.

A Case Report of Blau Syndrome / 罕见病研究

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).@*METHODS@#A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.@*RESULTS@#After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).@*CONCLUSIONS@#Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.

Role of podocyte injury signaling pathway in steroid-resistant nephrotic syndrome and research progress in traditional Chinese medicine intervention / 中国中药杂志

As one of the main diseases leading to end-stage renal disease, steroid-resistant nephrotic syndrome(SRNS) can cause serious complications such as infection. Without effective control, this disease can further lead to the malignant development of the renal function, bringing serious social and economic burdens. As previously reported, the formation of SRNS is mostly related to the podocyte injury in the body, i.e., the injury of glomerular visceral epithelial cells. Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, nuclear transcription factor-κB(NF-κB) signaling pathway, mammalian target of rapamycin(mTOR)/adenosine monophosphate(AMP)-activated protein kinase(AMPK), transforming growth factor(TGF)-β1/Smads, and other signaling pathways are classical signaling pathways related to podocyte injury. By regulating the expression of signaling pathways, podocyte injury can be intervened to improve the adhesion between podocyte foot processes and glomerular basement membrane and promote the function of podocytes, thereby alleviating the clinical symptoms of SRNS. Through the literature review, traditional Chinese medicine(TCM) has unique advantages and an important role in intervening in podocyte injury. In the intervention in podocyte injury, TCM, by virtue of multi-target and multi-pathway role, can regulate and intervene in podocyte injury in many ways, alleviate the clinical symptoms of SRNS, and interfere with the progress of SRNS, reflecting the unique advantages of TCM. On the other hand, TCM can directly or indirectly inhibit podocyte injury by regulating the above signaling pathways, which can not only promote the effect of hormones and immunosuppressants and shorten the course of treatment, but also reduce the toxic and side effects caused by various hormones and immunosuppressants to exert the advantages of small side effects and low price of TCM. This article reviewed TCM in the treatment of SRNS by interfering with podocyte injury-related signaling pathways and is expected to provide a reference for the in-depth study of TCM in the treatment of SRNS, as well as a theoretical basis and a new direction for the clinical application of TCM to shorten the course of treatment of SRNS and delay the progression to end-stage renal disease.