Foam dressing and micropower vacuum dressing promote diabetic foot ulcer wound healing by activating the PI3K/AKT/mTOR pathway in rats.

Foam dressing (FD) and micropower vacuum dressing (MVD) have been applied in the treatment of diabetic foot ulcer (DFU). However, research about the mode of action on the efficacy of the two dressings is extremely rare. This study proposed to explore the mechanism involved in diabetic wound healing under FD or MVD treatment. Macroscopical study was performed to evaluate the effectiveness of FD and MVD on wound healing in a rat model of DFU. Morphological analysis in the wound skin tissue was conducted by hematoxylin and eosin staining. Meanwhile, inflammatory cytokines in serum were measured by enzyme linked immunosorbent assay. The protein expression of phosphatidylinositol 3 kinase, protein kinase B and mammalian target of rapamycin (PI3K/AKT/mTOR) and their phosphorylation levels were determined by western blotting. We found that wound healing in rats with DFU was enhanced with the application of FD and MVD. The therapeutic efficacy of FD was superior to MVD. Compared with diabetic foot group, the concentrations of inflammatory cytokines, tumor necrosis factor alpha, interleukin-1ß and interleukin-6, were significantly down-regulated. Besides, the phosphorylation levels of PI3K, AKT and mTOR were up-regulated under FD or MVD treatment. We demonstrated that the treatment of FD and MVD effectively promoted the wound skin healing through activating the PI3K/AKT/mTOR pathway. Our research may provide a new idea for exploring the mode of action of dressing application in healing of DFU.

Case report: A rare combination of aldosterone-secreting adrenocortical carcinoma and papillary thyroid carcinoma with Graves' disease.

Adrenocortical carcinoma (ACC) is a rare malignancy originating in the adrenal glands, aldosterone-producing ACC, even rarer. Papillary thyroid carcinoma (PTC), by contrast, accounts for the majority of thyroid carcinomas. We herein describe the first reported case of a female with comorbidities of aldosterone-producing ACC, PTC, and Graves' Disease(GD). The patient achieved transient clinical remission following adrenalectomy. However, three months later, aldosterone-producing ACC lung metastases emerged. Subsequently, within another three-month interval, she developed thyroid eye disease(TED). The patient died roughly one year after the adrenal operation. Exome sequencing did not reveal associations between aldosterone-producing ACC, PTC, and GD, and the underlying concurrence mechanism has yet to be elucidated. Further research of similar cases are needed to confirm potential links between the three pathologies.

Ube2L6 Promotes M1 Macrophage Polarization in High-Fat Diet-Fed Obese Mice via ISGylation of STAT1 to Trigger STAT1 Activation.

INTRODUCTION: In obesity-related type 2 diabetes mellitus (T2DM), M1 macrophages aggravate chronic inflammation and insulin resistance. ISG15-conjugation enzyme E2L6 (Ube2L6) has been demonstrated as a promoter of obesity and insulin resistance. This study investigated the function and mechanism of Ube2L6 in M1 macrophage polarization in obesity. METHODS: Obesity was induced in Ube2L6AKO mice and age-matched Ube2L6flox/flox control mice by high-fat diet (HFD). Stromal vascular cells were isolated from the epididymal white adipose tissue of mice. Polarization induction was performed in mouse bone marrow-derived macrophages (BMDMs) by exposure to IFN-γ, lipopolysaccharide, or IL-4. F4/80 expression was assessed by immunohistochemistry staining. Expressions of M1/M2 macrophage markers and target molecules were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. Protein interaction was validated by co-immunoprecipitation (Co-IP) assay. The release of TNF-α and IL-10 was detected by ELISA. RESULTS: The polarization of pro-inflammatory M1 macrophages together with an increase in macrophage infiltration was observed in HFD-fed mice, which could be restrained by Ube2L6 knockdown. Additionally, Ube2L6 deficiency triggered the repolarization of BMDMs from M1 to M2 phenotypes. Mechanistically, Ube2L6 promoted the expression and activation of signal transducer and activator of transcription 1 (STAT1) through interferon-stimulated gene 15 (ISG15)-mediated ISGlylation, resulting in M1 macrophage polarization. CONCLUSION: Ube2L6 exerts as an activator of STAT1 via post-translational modification of STAT1 by ISG15, thereby triggering M1 macrophage polarization in HFD-fed obese mice. Overall, targeting Ube2L6 may represent an effective therapeutic strategy for ameliorating obesity-related T2DM.

Duplicated adrenal veins in primary aldosteronism misdiagnosed with ectopic aldosteronoma due to apparent bilateral aldosterone suppression.

BACKGROUND: Primary aldosteronism (PA) is considered the number one aetiology for secondary hypertension. Apart from confirmatory tests and localisation of PA determined by computed tomography (CT), adrenal venous sampling (AVS) is used to define whether aldosterone hypersecretion occurs inside one or both adrenal glands. However, even correctly-performed AVS may lead to undiagnostic results such as apparent bilateral adrenal suppression (apparent bilateral aldosterone suppression), in which the adrenal aldosterone-to-cortisol ratios (AC ratios) are decreased bilaterally compared to the peripheral blood sample, with several causes contributing to it. CASE DESCRIPTION: Here, we describe the case of a 48-year-old man who was referred to our department for further investigation with a history of refractory hypertension, hypokalaemia, and aortic dissection. His hypertension and hypokalaemia were initially attributed to ectopic aldosteronoma due to his adrenal CT scan and AVS results. However, the correct diagnosis of an adenoma with duplicated right adrenal veins (duplicated adrenal veins) due to apparent bilateral aldosterone suppression was confirmed during surgery. CONCLUSION: AVS is the gold standard accepted for PA subtyping, but sometimes when apparent bilateral aldosterone suppression is present, it can give ambiguous results. Duplicated right adrenal veins, may impact results, thus, AVS may not accurately provide evidence of unilateral hypersecretion for all PA patients. Repeat AVS or adrenal surgery can provide worthwhile diagnostic conclusions.

The recognition and diagnosis of primary aldosteronism (PA) have increased in recent years and clinicians usually require adrenal venous sampling (AVS) to identify the affected side, and it's crucial for further treatments of PA patients (surgery or medicine).We presented an example of unilateral aldosteronoma with duplicated adrenal veins whose AVS results suggested apparent bilateral aldosterone suppression (the adrenal venous aldosterone/cortisol ratios are bilaterally lower than the peripheral ratios). He was misdiagnosed with ectopic aldosteronoma due to computed tomography (CT) features, but surgery findings revealed duplicated adrenal veins.Unclear AVS results such as apparent bilateral aldosterone suppression can lead to a missed diagnosis of unilateral PA, preventing patients from receiving potentially curative adrenal resection.Our case can serve as an example for clinicians that encounter the same condition to provide further investigational clues to ensure the correct aetiological diagnosis for patients with PA.

A de novo pure 21q22.3 deletion in a 9-year-old boy with buried penis: a case report and literature review.

21q deletion has been associated with a wide range of clinical signs, from very mild to severe phenotypes, and with the progress of genetic technology, more patients with this deletion are being diagnosed. This study reports on a 9-year-old boy with a terminal deletion of 4.5 Mb on chromosome 21 in the locus of chr21: 43531239-48119895 (GRCh37/hg19). Dark skin, a buried penis, small testes, dental caries, microcephaly, a low auricle, mental and intellectual retardation, balance disorder and pituitary and callosum dysplasia were observed. The results of a literature review and observation of similar abnormalities, including hypoplasia of corpus callosum, in two patients with non-overlapping deletion regions suggest that there are multiple gene loci regulating brain development on 21q. By comparing the overlapped deletion region in 21q22.3 cases of brain anomalies and/or gonadal dysgenesis, we concluded there were two overlapped microdeletion regions (chr21:43531239-43792093 and chr21:46625055-46884297) that may be related to brain and gonadal development. The same 16.49 Mb deletion of chr21:31578129-48119895 (GRCh37/hg19) was shared in 10 cases, and 24 cases shared the same 5.59 Mb deletion of chr21:42478130-48119895 (GRCh37/hg19) in DECIPHER (Database of Chromasomal Imbalance and Phenotype in Humans using Ensembl Resources), suggesting these were two commonly deleted regions of pure partial 21q. Those patients with the same breakpoints had different phenotypes suggesting the heterogeneity of 21q deletion.

Establishing a novel colorectal cancer predictive model based on unique gut microbial single nucleotide variant markers.

Current metagenomic species-based colorectal cancer (CRC) microbial biomarkers may confuse diagnosis because the genetic content of different microbial strains, even those belonging to the same species, may differ from 5% to 30%. Here, a total of 7549 non-redundant single nucleotide variants (SNVs) were annotated in 25 species from 3 CRC cohorts (n = 249). Then, 22 microbial SNV markers that contributed to distinguishing subjects with CRC from healthy subjects were identified by the random forest algorithm to construct a novel CRC predictive model. Excitingly, the predictive model showed high accuracy both in the training (AUC = 75.35%) and validation cohorts (AUC = 73.08%-88.02%). We further explored the specificity of these SNV markers in a broader background by performing a meta-analysis across 4 metabolic disease cohorts. Among these SNV markers, 3 SNVs that were enriched in CRC patients and located in the genomes of Eubacterium rectale and Faecalibacterium prausnitzii were CRC specific (AUC = 72.51%-94.07%).

Metagenomic Analyses Expand Bacterial and Functional Profiling Biomarkers for Colorectal Cancer in a Hainan Cohort, China.

This study was conducted for the metagenomic analysis of stool samples from CRC affected individuals to identify biomarkers for CRC in Hainan, the only tropical island province of China. The gut microbiota of CRC patients differed significantly from that of healthy and reference database cohorts based on Aitchison distance and Bray-Cutis distance but there was no significant difference in alpha diversity. Furthermore, at the species level, 68 species were significantly altered including 37 CRC-enriched, such as, Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum, Citrobacter portucalensis, Alloprevotella sp., Shigella sonnei, Coriobacteriaceae bacterium, etc. Sixty-seven different metabolic pathways were acquired, and pathways involved in the synthesis of many amino acids were significantly declined. Besides, 2 identified antibiotic resistance genes performed well (area under the receive-operation curve AUC = 0.833, 95% CI 58.51-100%) compared with virulence factor genes. The results of the present study provide region-specific bacterial and functional biomarkers of gut microbiota for CRC patients in Hainan. Microbiota is considered as a non-invasive biomarker for the detection of CRC. Gut microbiota of different geographic regions should be further studied to expand the understanding of markers, especially for the China cohort due to diverse nationalities and lifestyles.

An adolescent girl with premature ovarian failure, Graves' disease, and chronic urticaria: a case report.

BACKGROUND: Premature ovarian failure is characterized by amenorrhea, hypoestrogenism, and hypergonadotropinism, and occurs in women under 40 years of age. The prevalence of premature ovarian failure in women younger than 20 years of age is only 0.01%. Immune disorders are one of the causes of premature ovarian failure. Graves' disease and chronic urticaria are also associated with immune disorders. CASE PRESENTATION: We report a case of a 15-year-old Han Chinese girl with premature ovarian failure complicated by Graves' disease and chronic urticaria. She experienced menarche at 13 years of age and presented with amenorrhea after 7 months of irregular menstruation. Laboratory examinations indicated hypoestrogenism and hypergonadotropinism. Ultrasound imaging revealed that her uterus and ovaries were small in size. Gene and antibody tests related to premature ovarian failure returned negative results. Both thyroid peroxidase autoantibody and thyrotropin receptor antibody were positive. After reviewing the literature on the relationship between these three diseases and immune disorders, our patient was diagnosed as having atypical autoimmune polyglandular syndrome. After taking small doses of estrogen for 6 months, the size of her uterus increased, and her psychological anxiety was relieved. CONCLUSIONS: We report a case of an unusual association of premature ovarian failure, Graves' disease, and chronic urticaria. This case presents an atypical combination of adolescent autoimmune polyglandular syndrome, which is worthy of the attention of clinicians and presents an important lesson for them. Our case highlights that premature ovarian failure in adolescents requires long-term follow-up and medical treatment as well as psychological counselling.

Type A insulin resistance syndrome misdiagnosed as polycystic ovary syndrome: a case report.

BACKGROUND: Type A insulin resistance syndrome, one type of the hereditary insulin resistance syndromes, is a rare disorder. Patients with type A insulin resistance syndrome are nonobese and demonstrate severe hyperinsulinemia, hyperandrogenism, and acanthosis nigricans. The clinical features are more severe in affected females than in males, and they mostly become apparent at the age of puberty. In many cases, when severe insulin resistance is covered up by other signs or symptoms of type A insulin resistance syndrome, patients are often easily misdiagnosed with other diseases, such as polycystic ovary syndrome. CASE PRESENTATION: Our patient was a 27-year-old Han Chinese woman who sought treatment because of a menstrual disorder and hirsutism. Tests showed that her levels of insulin and testosterone were elevated, and gynecological color Doppler ultrasound suggested multiple cystic changes in the bilateral ovaries. After a diagnosis of polycystic ovary syndrome was made, pulsatile gonadotropin-releasing hormone therapy and metformin were administered, but the patient's symptoms did not improve in 1 year of follow-up. Considering that the previous diagnosis might have been incorrect, venous blood samples were collected from the patient and her relatives for genetic analysis. Subsequently, using Illumina sequencing, it was found that the proband, her father, and two brothers all had the c.3601C>T heterozygous missense mutation in exon 20 of the insulin receptor gene. The diagnosis was corrected to type A insulin resistance syndrome, and the patient's treatment was modified. CONCLUSION: We report a case of a young woman with type A insulin resistance syndrome that was misdiagnosed as polycystic ovary syndrome. We discuss the causes, clinical features, diagnosis, and treatment of type A insulin resistance syndrome to improve the recognition of the disease and reduce its misdiagnosis. Female patients with high androgen levels and severe hyperinsulinemia should be considered for the possibility of hereditary insulin resistance syndromes (such as type A insulin resistance syndrome). Gene sequencing helps in making an early diagnosis and developing a targeted treatment strategy.

Osteogenic ability of bone marrow stem cells intraoperatively enriched by a novel matrix.

Poly-L-lysine (PLL) is commonly used as an adhibiting agent due to its good viscosity, and demineralized bone matrix (DBM) is a common enriched matrix for selective cell retention technology. Therefore, the aim of this study was to use PLL to coat the surface and interspaces of DBM to form a novel type of enriched matrix [DBM coated with PLL (PLL-DBM)], in order to effectively improve the enrichment effects of bone marrow stem cells and enhance their osteogenic ability. Electron microscope scanning and the infrared spectrum were used to observe the structure of PLL-DBM and the optimal conditions for the combination of PLL and DBM. Enriching effects on bone marrow nucleated cells (NCs) and platelets (PLTs) were detected with an automated hematology analyzer. The osteogenesis of the following four groups was assessed with a grafting bone model in a goat spinal transverse process: IA, tissue engineered bone (TEB) fabricated following enrichment of bone marrow with PLL-DBM; IB, autogenous iliac bone; IIC, TEB fabricated following enrichment of bone marrow with DBM; IID, blank DBM. The goats were sacrificed in one batch at week 16 after the surgery and the fusion specimens were examined using X-ray and three-dimensional computed tomography (CT). In addition, the CT value was determined and the histology and biomechanics were analyzed in order to evaluate the osteogenic ability. The results showed that PLL and DBM combined well and that PLL-DBM exhibited a natural mesh pore structure. The fold enrichment of NCs and PLTs with PLL-DBM was significantly higher than that with DBM. The fusion effects of the IA and IB groups were similar and significantly enhanced compared with those of the IIC and IID groups. The results confirmed that PLL-DBM is an ideal enriched matrix for bone marrow stem cells, and TEB rapidly fabricated by PLL-DBM intraoperatively enriched bone marrow stem cells exhibits an improved osteogenic ability.

[Reverse anterolateral thigh flap for repair of wound defects with exposed tibia].

OBJECTIVE: To investigate the method and effectiveness of reverse anterolateral thigh flap and muscle flap for repair of wound defects with exposed tibia in the proximal-middle leg. METHODS: Between October 2005 and April 2010, 16 patients with wound defects with exposed tibia in the proximal-middle leg were treated with reverse anterolateral thigh flap and muscle flap. There were 10 males and 6 females, aged from 16 to 52 years. Injury was caused by traffic accident in 11 cases and by crushing in 5 cases. The disease duration of 1-6 hours (mean, 3 hours) in 10 patients and 6-14 days (mean, 10 days) in 6 patients, who underwent tibial fracture plate fixation in other hospitals. The size of wound ranged from 13 cm x 7 cm to 20 cm x 13 cm. The size of the flap ranged from 16 cm x 10 cm to 23 cm x 15 cm. The donor sites were covered with splite thickness skin grafts. RESULTS: Infection occurred in 2 flaps at 5-7 days and was cured after 1 week of dressing change; the other flaps survived and the wounds healed by first intention. The incisions healed well and the skin grafts survived at the donor sites. All cases were followed up 10-23 months (mean, 18 months). The appearance of the flap was slightly overstaffed, but the color and texture were satisfactory. All fractures healed at 8-10 months after operation. CONCLUSION: It is effective to repair wound defects with exposed tibia in the proximal-middle leg with reverse anterolateral thigh flap and muscle flap.