Intestinal flora and linear growth in children.

The gut microbiota plays a critical role in human growth and development as well as the regulation of human pathophysiological processes. According to research, the gut microbiota controls the host's growth and development in areas such as nutrition, metabolism, endocrine hormones, and immune modulation. The human gut microbiota has an important role in child and adolescent growth, especially when nutritional conditions are poor. In this review, we focus on recent findings about the gut microbiota's influence on child growth, including the relationship between the gut microbiota and linear growth during pregnancy, infancy, childhood, and adolescence. Furthermore, we also review some mechanisms by which intestinal flora influence the host's linear growth. Although the data supports a link between intestinal flora and linear development in children, our review has limitations that prohibit us from fully verifying the causal relationship between gut flora and linear development in children. Improving the gut microbiota, in conjunction with renutrition techniques, has the potential to ameliorate the growth and development impairments currently associated with chronic illness and malnutrition in children.

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions.

Cirrhosis predisposes to abnormalities in energy, hormonal, and immunological homeostasis. Disturbances in these metabolic processes create susceptibility to sarcopenia or pathological muscle wasting. Sarcopenia is prevalent in cirrhosis and its presence portends significant adverse outcomes including the length of hospital stay, infectious complications, and mortality. This highlights the importance of identification of at-risk individuals with early nutritional, therapeutic and physical therapy intervention. This manuscript summarizes literature relevant to sarcopenia in cirrhosis, describes current knowledge, and elucidates possible future directions.

Role of hormones in bone remodeling in the craniofacial complex: A review.

Background: Diseases such as periodontitis and osteoporosis are expected to rise tremendously by 2050. Bone formation and remodeling are complex processes that are disturbed in a variety of diseases influenced by various hormones. Objective: This study aimed to review and present the roles of various hormones that regulate bone remodeling of the craniofacial complex. Methods: A literature search was conducted on PubMed and Google Scholar for studies related to hormones and jawbone. Search strategies included the combinations ("name of hormone" + "dental term") of the following terms: "hormones", "oxytocin", "estrogen", "adiponectin", "parathyroid hormone", "testosterone", "insulin", "angiotensin", "cortisol", and "erythropoietin", combined with a dental term "jaw bone", "alveolar bone", "dental implant", "jaw + bone regeneration, healing or repair", "dentistry", "periodontitis", "dry socket", "osteoporosis" or "alveolitis". The papers were screened according to the inclusion criteria from January 1, 2000 to March 31, 2021 in English. Publications included reviews, book chapters, and original research papers; in vitro studies, in vivo animal, or human studies, including clinical studies, and meta-analyses. Results: Bone formation and remodeling is a complex continuous process involving many hormones. Bone volume reduction following tooth extractions and bone diseases, such as periodontitis and osteoporosis, cause serious problems and require a great understanding of the process. Conclusion: Hormones are with us all the time, shape our development and regulate homeostasis. Newly discovered effects of hormones influencing bone healing open the possibilities of using hormones as therapeutics to combat bone-related diseases.

Seamless and early gap healing of osteochondral defects by autologous mosaicplasty combined with bioactive supramolecular nanofiber-enabled gelatin methacryloyl (BSN-GelMA) hydrogel.

Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice. Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface, graft necrosis and sclerosis. However, poor gap integration is a serious concern, which eventually leads to deterioration of joint function. To deal with such complications, this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl (GelMA) hydrogel (BSN-GelMA). A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty, as early as six weeks. Moreover, the International Cartilage Repair Society score, histology score, glycosaminoglycan content, subchondral bone volume, and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group. This improved outcome was due to bio-interactive materials, which acted as tissue fillers to bridge the gap, prevent cartilage degeneration, and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel. This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty. It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.

Aromatase deficiency in a tall man: Case report of two novel mutations and review of literature.

Aromatase (CYP19A1) is the only enzyme known to catalyse the conversion of androgen to estrogen. Aromatase deficiency occurs due to mutation in CYP19A1gene which has an autosomal recessive inheritance pattern. It leads to decrease in estrogen synthesis and delayed epiphyseal closure, eunuchoid habitus and osteopenia. We are presenting here, a 24 years old male, with history of progressive increase in height and knock knees. X-ray showed open wrist and knee epiphysis. The serum testosterone level was normal and serum estradiol level was undetectable. Semen analysis showed azoospermia. Clinical exome sequencing gave two novel mutations in CYP19A1. The first variant was a novel single nucleotide deletion of thiamine at 570th base of the cDNA (c.570delT) of CYP19A1 gene. The second variant detected was again a novel one in the same gene in Exon 5 corresponding 344th base of the cDNA (c344G>A) resulting in a missense mutation of 115th arginine to glutamine in the protein. Sanger sequencing showed that the later mutation was inherited from the father. The patient was started on oral estradiol valerate for epiphyseal closure to prevent further increase in height. Only 15 mutations have been reported in the aromatase gene in males till date, our report of these novel mutations will be an add-on to the literature.

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain.

Context: Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. Objective: This study aimed at identifying predictors of response to SRL in elderly patients. Design: Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. Results: One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4-91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01-0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71-0.94). Conclusions: The most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis ≤6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL.

The value of plasma insulin-like growth factor 1 and interleukin-18 in the diagnosis of bronchopulmonary dysplasia in premature infants.

Objective: To explore the diagnostic value of IGF-1 and IL-18 in premature infants with BPD. Methods: Through a prospective observational study, the serum samples of infants in the BPD group and the non-BPD group were collected at different targeted time points, and the serum IGF-1 and IL-18 concentrations were dynamically monitored by ELISA. The Student t-test and one-way analysis of variance were adopted to analyze data, and the receiver operating characteristic (ROC) curve was used to test the diagnostic value. Result: A total of 90 VLBW premature infants admitted to NICU between January 2020 and 2021 were finally included. Compared with the non-BPD group, infants diagnosed with BPD had a significantly lower serum concentration of IGF-1 (P < 0.05) but a higher level of IL-18 (P < 0.05) on days 1, 7, 14, and 28 after birth. With the ROC curve analysis, the serum concentration IGF-1 on day 14 and IL-18 on day 28 reported high sensitivity and specificity to predict the risk of BPD (IGF-1: sensitivity: 89.29%, specificity: 77.78%, AUC: 0.8710; IL-18: sensitivity: 53.57%, specificity: 83.33%, AUC: 0.7887). And more substantial predictive power was found in combined analysis of IGF-1 and serum IL-18 on day 14: the sensitivity was 91.07% and the specificity was 83.33%, with the AUC of 0.9142. Conclusion: IGF-1 and IL-18 might be closely involved in the occurrence and development of BPD. The serum concentration of IGF-1 combined with IL-18 could be potentially sensitive markers for the early diagnosis and severity of BPD.

A Novel Case of Hyperglycemic Hyperosmolar State After the Use of Teprotumumab in a Patient With Thyroid Eye Disease.

Background/Objective: Teprotumumab, a novel treatment for thyroid eye disease (TED), which blocks the insulin-like growth factor 1 receptor, has been associated with improvement in proptosis and inflammatory ocular symptoms. In the original trials, hyperglycemia was reported in 5% to 12% of patients; however, none required hospitalization. We report a case of hyperglycemic hyperosmolar state after the first infusion of teprotumumab. Case Report: A 56-year-old woman with Graves' disease, severe thyroid eye disease, and prediabetes presented with polyuria, polydipsia, nausea, abdominal pain, headache, dizziness, and a fall to the emergency department 3 weeks after her first teprotumumab infusion. She was noted to have serum glucose levels of 939 mg/dL, serum bicarbonate levels of 28 meq/dL, serum osmolality of 324 mOsm/kg, and trace ketones in urine. She was treated with intravenous fluids and insulin with subsequent improvement in clinical status and biochemical profile. She was then discharged on multiple daily injections of insulin. Discussion: Hyperglycemia is a known adverse effect of insulin-like growth factor 1 receptor inhibitors like teprotumumab. The incidence of hyperglycemia in the original trials was 5% to 12%. Most cases were mild and resolved with titration of current diabetes medications. No cases of hospitalization due to severe hyperglycemia or hyperglycemic hyperosmolar state have been reported until now. Conclusion: We intend to highlight the severity of hyperglycemia that could occur with the use of teprotumumab and the need for research to evaluate the true incidence of this condition.

Sparsely Granulated Corticotroph Pituitary Macroadenoma Presenting With Pituitary Apoplexy Resulting in Remission of Hypercortisolism.

Objective: Pituitary corticotroph macroadenomas, which account for 7% to 23% of corticotroph adenomas, rarely present with apoplexy. This report aimed to describe a patient with a sparsely granulated corticotroph tumor (SGCT) presenting with apoplexy and remission of hypercortisolism. Case Report: A 33-year-old male patient presented via ambulance with sudden onset of severe headache and nausea/vomiting. Physical examination revealed bitemporal hemianopsia, diplopia from right-sided third cranial nerve palsy, abdominal striae, facial plethora, and dorsal and supraclavicular fat pads. Magnetic resonance imaging demonstrated a 3.2-cm mass arising from the sella turcica with hemorrhage compressing the optic chiasm, extension into the sphenoid sinus and cavernous sinus. Initial investigations revealed a plasma cortisol level of 64.08 (reference range [RR], 2.36-17.05) mcg/dL. He underwent emergent transsphenoidal surgery. Pathology was diagnostic of SGCT. Postoperatively, the following laboratory findings were found: (1) cortisol level, <1.8 ug/dL (RR, 2.4-17); (2) adrenocorticotropic hormone level, 36 pg/mL (RR, 0-81); (3) thyroid-stimulating hormone level, 0.07 uIU/mL (RR, 0.36-3.74); (4) free thyroxine level, 1 ng/dL (RR, 0.8-1.5); (5) luteinizing hormone level, <1 mIU/mL (RR, 1-12); (6) follicle-stimulating hormone level, 1 mIU/mL (RR, 1-12); and (7) testosterone level, 28.8 ng/dL (RR, 219.2-905.6), with ongoing requirement for hydrocortisone, levothyroxine, testosterone replacement, and continued follow-up. Discussion: Corticotroph adenomas are divided into densely granulated, sparsely granulated, and Crooke cell tumors. Sparsely granulated pattern is associated with a larger tumor size and decreased remission rate after surgery. Conclusion: This report illustrates a rare case of hypercortisolism remission due to apoplexy of an SGCT with subsequent central adrenal insufficiency, hypothyroidism, and hypogonadism.

Genistein promotes M1 macrophage apoptosis and reduces inflammatory response by disrupting miR-21/TIPE2 pathway.

Cardiovascular diseases are a major cause of mortality, and vascular injury, a common pathological basis of cardiovascular disease, is deeply correlated with macrophage apoptosis and inflammatory response. Genistein, a type of phytoestrogen, exerts cardiovascular protective activities, but the underlying mechanism has not been fully elucidated. In this study, RAW264.7 cells were treated with genistein, lipopolysaccharide (LPS), nuclear factor-kappa B (NF-κB) inhibitor, and/or protein kinase B (AKT) agonist to determine the role of genistein in apoptosis and inflammation in LPS-stimulated cells. Simultaneously, high fat diet-fed C57BL/6 mice were administered genistein to evaluate the function of genistein on LPS-induced cardiovascular injury mouse model. Here, we demonstrated that LPS obviously increased apoptosis resistance and inflammatory response of macrophages by promoting miR-21 expression, and miR-21 downregulated tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) expression by targeting the coding region. Genistein reduced miR-21 expression by inhibiting NF-κB, then blocked toll-like receptor 4 (TLR4) pathway and AKT phosphorylation dependent on TIPE2, resulting in inhibition of LPS. Our research suggests that miR-21/TIPE2 pathway is involved in M1 macrophage apoptosis and inflammatory response, and genistein inhibits the progression of LPS-induced cardiovascular injury at the epigenetic level via regulating the promoter region of Vmp1 by NF-κB.

Gestational Diabetes Mellitus and Energy-Dense Diet: What Is the Role of the Insulin/IGF Axis?

Gestational diabetes mellitus (GDM), is one of the most important pregnancy complications affecting approximately 15% of pregnant women. It is related to several gestational adverse outcomes in the fetus, e.g., macrosomia, shoulder dystocia, stillbirth, neonatal hypoglycemia, and respiratory distress. Women with GDM have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors could contribute to its development: ß-cell dysfunction and failure in insulin secretion in response to insulin resistance induced by gestation. Both processes, together with the physiological activities of the insulin-like growth factors (IGFs), play a crucial role in glucose transport to the fetus and hence, fetal growth and development. IGFs (both IGF-1 and IGF-2) and their binding proteins (IGFBPs) regulate glucose metabolism and insulin sensitivity. Maternal nutritional status determines the health of the newborn, as it has substantial effects on fetal growth and development. Maternal obesity and an energy-dense diet can cause an increase in insulin and IGF-1 serum levels, producing metabolic disorders, such as insulin resistance, GDM, and high birth weight (> 4,000 g) due to a higher level of body fat. In this way, in GDM pregnancies there is an increase in IGF-1 and IGF-2 serum levels, and a decrease in IGFBP-1 and 4 serum levels, suggesting the crucial role of the insulin/IGF system in this gestational outcome. Here, the present review tries to elucidate the role that energy-dense diets and the insulin/IGF-1 signaling pathway perform in GDM pregnancies.

A Case of Hypophysitis Associated With SARS-CoV-2 Vaccination.

Background/Objective: Although SARS-CoV-2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathy in relation to SARS-CoV-2 vaccination. Here we report a rare case of hypophysitis with acute onset of diabetes insipidus, immediately after SARS-CoV-2 vaccination. Case Report: A 48-year-old female patient had been in her usual state of health until she received the first SARS-CoV-2 vaccine. Two days after vaccination, she started to have flu-like symptoms, including severe headache and myalgia as well as persistent headache, polydipsia, and polyuria. She was diagnosed with diabetes insipidus, and magnetic resonance imaging revealed thickening of the pituitary stalk. Three months after vaccination, her symptoms had somewhat improved, but she still had pituitary stalk thickening on magnetic resonance imaging. Discussion: Given the timing of the occurrence of diabetes insipidus, we believe that the patient's hypophysitis may be associated with SARS-CoV-2 vaccination. We also found 19 cases of endocrinopathy after SARS-CoV-2 vaccination by literature search. The reported endocrine organs were the thyroid, pituitary, and adrenals. Twelve cases of diabetes were also reported. Among 3 pituitary cases, diabetes insipidus was reported only in our case. Conclusion: We report a rare case of SARS-CoV-2 vaccine-triggered hypophysitis, which led to diabetes insipidus. SARS-CoV-2 vaccine-related endocrinopathy seems, indeed, possible. Endocrinopathy is associated with infrequent complications; however, it may be underestimated in the post-SARS-CoV-2-vaccinated population. Further studies are warranted to better understand SARS-CoV-2 vaccine-related endocrinopathy.

Diet and acne: A systematic review.

Background: Acne vulgaris is a common cutaneous disorder. Diet and metabolism, specifically glycemic content and dairy, influence hormones such as insulin, insulin-like growth factor 1, and androgens, which affect acnegenesis. Objective: To systematically review high-quality evidence regarding the association of dietary glycemic and dairy intake with acnegenesis. Methods: A comprehensive literature search, without timeline restriction, of MEDLINE (completed between October and November 2021) for English-language papers that examined the association between diet and acne was conducted. The evidence quality was assessed using the Ottawa quality assessment scale. Results: The literature search yielded 410 articles, of which 34 articles met the inclusion criteria. The literature on whether dairy product intake is associated with acnegenesis is mixed and may be dependent on sex, ethnicity, and cultural dietary habits. High glycemic index and increased daily glycemic load intake were positively associated with acnegenesis and acne severity, an observation supported by randomized controlled trials. Conclusion: High glycemic index, increased glycemic load, and carbohydrate intake have a modest yet significant proacnegenic effect. Increased dairy consumption may have been proacnegenic in select populations, such as those in which a Western diet is prevalent. The impact of diet on acnegenesis is likely dependent on sex and ethnicity. Further randomized trials are necessary to fully characterize the potential associations.

Recurrent Acromegaly in a Patient With a CHEK2 Mutation.

Background/Objective: CHEK2 is a cell-cycle checkpoint kinase and is part of the ATM-CHEK2-p53 cascade, which is protective against carcinogenesis. We describe a germline CHEK2 mutation in a patient with acromegaly and other tumors. Case Report: We present a woman with a germline CHEK2∗ 110delC mutation previously diagnosed with fibroadenoma of the breast and papillary thyroid carcinoma. She presented with acromegaly at age 48 (insulin-like growth factor 1, 556 mcg/L [reference range, 90-360] and lack of growth hormone suppression on glucose tolerance testing) and underwent transsphenoidal resection of a somatotroph microadenoma. Four years after surgery, she developed recurrent growth hormone excess. She was treated with cabergoline, which was discontinued due to intolerance, and transitioned to lanreotide depot, which was switched to pegvisomant because of prediabetes. Her insulin-like growth factor 1 levels remained normal on pegvisomant. Follow-up magnetic resonance imaging examinations showed no evidence of tumor progression. Shortly after the diagnosis of acromegaly, the patient was diagnosed with endometrial carcinoma, bilateral ovarian cystadenomas, and uterine leiomyomas. She was additionally found to have a nonfunctioning adrenal nodule and hyperplastic and adenomatous colon polyps. There are multiple family members with malignancies, including colon, thyroid, and lung cancer. Discussion: This is a novel report of a patient with a pathogenic germline CHEK2 mutation and multiple malignant and benign tumors, including recurrent acromegaly. Conclusion: Our data raise the possibility that CHEK2 mutations may be involved in the development of acromegaly. Additional studies are needed to elucidate the potential role of CHEK2 mutations in the pathogenesis of somatotroph adenomas.

Sirt3 Pharmacologically Promotes Insulin Sensitivity through PI3/AKT/mTOR and Their Downstream Pathway in Adipocytes.

Sirtuin-3 (Sirt3) is a major mitochondrial deacetylase enzyme that regulates multiple metabolic pathways, and its expression is decreased in diabetes type 1 and type 2 diabetes. This study aimed to elucidate Sirt3's molecular mechanism in regulating insulin sensitivity in adipocytes that can contribute to the effort of targeting Sirt3 for the treatment of obesity and type 2 diabetes. We found that the Sirt3 activator honokiol (HNK) induced adipogenesis compared to the control, in contrast to Sirt3 inhibitor, 3-TYP. Accordingly, HNK increased expression of adipocyte gene markers, gene-involved lipolysis and glucose transport (GLUT4), while 3-TYP reduced expression of those genes. Interestingly, 3-TYP caused an increase in gene expression of adipocyte-specific cytokines including IL6, resistin, and TNF-α. However, changes in adipocyte-specific cytokines in HNK treated cells were not significant. In addition, HNK stimulated insulin pathway by promoting insulin receptor beta (IRß) and PI3K/AKT/mTOR pathways, resulting in an increase in phosphorylation of the forkhead family FoxO1/FoxO3a/FoxO4 and glycogen synthase kinase-3 (GSK-3ß), opposing 3-TYP. In line with these findings, HNK increased free fatty acid and glucose uptake, contrary to 3-TYP. In conclusion, Sirt3 activator-HNK induced adipogenesis and lipolysis reduced adipocytes specific cytokines. Intriguingly, HNK activated insulin signaling pathway and increased free fatty acid as well as glucose uptake and transport, in sharp contrast to 3-TYP. These results indicate that, via insulin signaling regulation, Sirt3 activation by HNK improves insulin resistance, while Sirt3 inhibition by 3-TYP might precipitate insulin resistance.

Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.

Periosteum and development of the tissue-engineered periosteum for guided bone regeneration.

BACKGROUND: Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques. METHODS: This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized. RESULTS: The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair. CONCLUSIONS: Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.

Cystic fibrosis related liver disease and endocrine considerations.

Cystic fibrosis-liver disease (CFLD) is one of the most common non-pulmonary complications in the CF population, is associated with significant morbidity and represents the third leading cause of mortality in those with CF. CFLD encompasses a broad spectrum of hepatobiliary manifestations ranging from mild transaminitis, biliary disease, hepatic steatosis, focal biliary cirrhosis and multilobular biliary cirrhosis. The diagnosis of CFLD and prediction of disease progression remains a clinical challenge. The identification of novel CFLD biomarkers as well as the role of newer imaging techniques such as elastography to allow for early detection and intervention are active areas of research focus. Biliary cirrhosis with portal hypertension represents the most severe spectrum of CFLD, almost exclusively develops in the pediatric population, and is associated with a decline in pulmonary function, poor nutritional status, and greater risk of hospitalization. Furthermore, those with CFLD are at increased risk for vitamin deficiencies and endocrinopathies including CF-related diabetes, CF-related bone disease and hypogonadism, which can have further implications on disease outcomes and management. Effective treatment for CFLD remains limited and current interventions focus on optimization of nutritional status, identification and treatment of comorbid conditions, as well as early detection and management of CFLD specific sequelae such as portal hypertension or variceal bleeding. The extent to which highly effective modulator therapies may prevent the development or modify the progression of CFLD remains an active area of research. In this review, we discuss the challenges with defining and evaluating CFLD and the endocrine considerations and current management of CFLD.