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Background: Long term high fat diets (HFD) promote skin aging pathogenesis, but detailed mechanisms remain unclear especially for inflammaging, which has recently emerged as a pathway correlating aging and age-related disease with inflammation. p16INK4a (hereafter termed p16) inhibits the cell cycle, with p16 deletion significantly inhibiting inflammaging. We observed that HFD-induced p16 overexpression in the skin. Therefore, we investigated if p16 exacerbated inflammaging in HFD-induced skin and also if p16 deletion exerted protective effects against this process. Methods: Eight-week-old double knockout (KO) ApoE-/-p16-/- mice and ApoE-/- littermates were fed HFD for 12 weeks and their skin phenotypes were analyzed. We measured skin fibrosis, senescence-associated secretory phenotype (SASP) levels, and integrin-inflammasome pathway activation using histopathological, RNA-sequencing (RNA-seq), bioinformatics analysis, and molecular techniques. Results: We found that HFD contributed to inflammaging in the skin by activating the NLRP3 inflammasome pathway, increasing inflammatory infiltration, and promoting apoptosis by balancing expression between proapoptotic and antiapoptotic molecules. p16 knockout, when compared with the ApoE-/- phenotype, inhibited skin fibrosis by ameliorating inflammatory infiltration and proinflammatory factor expression (Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)), and also alleviated inflammaging skin progress induced by HFD in the ApoE-/- mouse model. RNA-seq showed that p16 KO mice inhibited both integrin-inflammasome and NF-κB proinflammatory pathway activation. Conclusions: p16 deletion or p16 positive cell clearance could be a novel strategy preventing long term HFD-induced skin aging.

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The present study aimed to explore the effects and clinical importance of serum interleukin (IL) IL-1ß, IL-6, C-reactive protein (CRP), intercellular adhesion molecule (ICAM)-1 and matrix metalloproteinase (MMP)-2 in patients with acute cerebral infarction undergoing intravenous thrombolysis during simultaneous hypothermia therapy. A total of 80 patients with acute cerebral infarction who were treated at our hospital were randomly selected. They were divided into groups A and B. The two groups were treated with intravenous thrombolysis, while group B received sub-hypothermia treatment. Prior to treatment and at 7 days after treatment, 5 ml of venous blood was collected and stored in a freezer at -80˚C. IL-1ß, IL-6, CRP, ICAM-1 and MMP-2 levels were detected by ELISA and compared between the groups and time-points. The results were as follows: i) At 7 days after treatment, the levels of IL-1ß, IL-6, CRP, ICAM-1 and MMP-2 in group B were significantly decreased compared with those in group A (P<0.05), while there was no significant difference of these levels between group A and B before treatment (P>0.05). The incidence of adverse reactions in group A and group B was 35 and 20% respectively, and the mortality rate was 10 and 5%, respectively. There were no significant differences in adverse events and mortality between the two groups (P>0.05). In addition, a positive correlation of the level of IL-1ß, IL-6, CRP, ICAM-1 and MMP-2 with the National Institutes of Health Stroke Scale score was determined in the patients prior to treatment. In conclusion, mild hypothermia treatment in addition to intravenous thrombolysis significantly reduced the levels of IL-1ß, IL-6, CRP, ICAM-1 and MMP-2 in patients with acute cerebral infarction and reduced inflammation, and should therefore be incorporated in clinical practice.

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Panaxatriol saponins (PTS) have a long history in the treatment of stroke. In our previous experiments, PTS has been found to alleviate ischemic stroke and play a role through regulating the inflammatory response, but the specific mechanism of its regulation is still unclear. Cell viability was determined by MTT assay. Expressions of polarization-related proteins CD16, CD68, ARG1 and CD206; inflammatory factors interleukin-1ß (IL-1ß); inducible nitric oxide synthase (iNOS); monocyte chemotactic protein 1(MCP-1) and cyclooxygenase-2 (COX-2); apoptosis-related proteins pro-caspase3; bax; caspase3 and bcl-2; and STAT3 and p-STAT3 were detected by western blot. ELISA was used to detect the expression of inflammatory-related factors in cells. The apoptosis rate was detected by flow cytometry. We found that the survival rate of oxygen sugar deprivation/reoxygenation (OGD/R) cells increased obviously after PTS treatment in a dose-dependent manner. PTS can promote M2 polarization of microglial cells (BV2) and inhibit inflammatory response of OGD/R cells, accompanied by decreased expression of inflammatory factors IL-1ß, iNOS, MCP-1, and COX-2. PTS inhibited apoptosis of OGD/R cells and was accompanied by decreased expression of apoptotic proteins Bax and caspase3 and increased expression of Bcl-2. We also found that PTS activated STAT3 levels in BV2 cells. After the addition of STAT3 inhibitor Stattic, it was found that PTS could promote M2 polarization of BV2 cells by activating the STAT3 pathway, thus inhibiting cell inflammation and apoptosis. PTS promoted M2 polarization in microglia cells by activating the STAT3 pathway, thereby reducing cell inflammation and apoptosis after glucose/oxygen deprivation.

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A 41-year-old female visited Ruijin Hospital because her face was swollen for more than 2 months. The patient was initially diagnosed with Cushing's disease (CD). Several examinations, including a dexamethasone suppression test (DST) at 2 mg and 8 mg, pituitary MRI, abdominal CT, punch biopsy of adrenal masses, and bilateral inferior petrosal sinus sampling (BIPSS), were performed, but the findings were not consistent with the clinical presentation. Ultimately, the patient underwent surgery and recovered. In this case, BIPSS was a useful way to diagnosis CD and suggested the exact location of a pituitary adenoma to Neurosurgery. BIPSS should be a required test for cases of CD that cannot be definitively diagnosed with just an MRI and 8 mg DST before surgery.

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Pituitary adenomas are common benign intracranial neoplasms representing about 10-25% of all intracranial neoplasm. Significant morbidity can occur along with pituitary adenomas due to hormonal dysfunction and mass effects. The pathogenesis of pituitary adenoma is unclear, however, etiologic factors include genetic events, hormonal stimulation, and growth factors [1], all of which promote cell proliferation and transformation in the tumor. However, genetic events play the most important role in tumorigenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, not only have function in pituitary cell proliferation and apoptosis but also in neoplastic transformation. It has been shown that miRNAs are differentially expressed in pituitary adenoma when compared with the normal pituitary gland; moreover, miRNAs have been identified as a predictive signature of pituitary adenoma and can be used to predict the histotype. The expression of miRNAs can be used not only to differentiate microadenomas from macroadenomas, but to also distinguish samples of treated patients from samples of non-treated patients. Therefore, we hypothesized that a miRNA-based network may be involved in pituitary tumorigenesis and it can potentially serve as useful diagnostic markers to improve the classification of pituitary adenomas. Here, we reviewed the therapeutic potential that different types of miRNAs may play in tumorigenesis. Moreover, miRNAs may emerge as potential therapeutic targets. We speculated the mechanism of miR-21 is involved in tumorigenesis, leading to improvements in therapies and prevention of metastasis.

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OBJECTIVE: Most patients with Cushing's disease (CD) will have evidence of an adenoma on high-resolution magnetic resonance imaging (MRI). However, a significant minority of patients with CD and biochemical hypercortisolaemia have no visible adenoma on MRI. The purpose of this study was to evaluate the diagnostic value of preoperative biochemical assessment and accuracy of MRI findings on surgical outcome. DESIGN: Retrospective data set analyses. PATIENTS AND MEASUREMENT: The clinical, endocrinological, histopathological and surgical outcomes of 24 consecutive CD patients with negative MRI findings were compared with those of 95 consecutive age- and sex-matched CD patients with pituitary adenomas on MRI. RESULTS: The total remission rate was 86.6%. Among all patients, 87 had concordant positive endocrine tests and underwent neurosurgery, while bilateral inferior petrosal sinus sampling (BIPSS) was performed in 12 and 50 other patients with negative and positive MRI, respectively. A pituitary adenoma, confirmed by pathological examination, was found in 83.3% and 93.6% of patients with negative and positive MRI, respectively. The remission rate was not different between patients with negative and positive MRI (87.5 % and 86.3%, respectively; P > 0.05) or between patients who did not undergo BIPSS with negative MRI and patients with positive MRI (P > 0.05). The remission rate of patients who underwent BIPSS with negative MRI was not different from those not undergoing BIPSS (P > 0.05). The recurrence rate was higher, although not statistically different, in patients with negative MRI compared to positive ones. CONCLUSIONS: Based on the findings outlined, MRI-negative CD may be a surgically remediable syndrome, with a pathophysiological basis that primarily involves a pituitary cause of the hypercortisolaemia.

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OBJECTIVE: To investigate how smoking was affecting the prevalence of sleep apnea/ hypopnea syndrome (SAHS) among adults aged over 30 years in Chengde city of Hebei province. METHODS: 1168 subjects, over 30 years of age were derived from a random sample from a community-based population in Shuangqiao district of Chengde city. All subjects responded to a questionnaire at their own houses regarding their habits of snoring and smoking. 1168 subjects (95.2%) answered the questions satisfactorily. RESULTS: (1) Among the smoking groups, the prevalence of snoring was 69.09%, higher than that in the nonsmoking groups 45.07% (P = 0.000). (2) In males, the smoking group had a higher prevalence (69.72%) of snoring than in the nonsmoking group (60.80%, P = 0.033). (3) Females in the smoking group had a higher prevalence of snoring (61.80%) than in the nonsmoking group (39.70%, P = 0.011). (4) The prevalence of snoring in males (60.80%) was significantly higher than that in females (39.70%, P = 0.000). (5) The prevalence (69.72%) of snoring in smoking males was similar to that in smoking females (61.80%, P = 0.336). (6) Data from logistic regression analysis indicated that smoking was one of the factors affecting snoring. (7) According to the degree of snoring, 127 moderate and severe snorers were measured by portable PSG for a whole night and the prevalence of SAHS was estimated. According to the AHI > or = 5 and the ESS > or = 9 cutoff-points, the prevalence rates of SAHS in smoking groups were both significantly higher than that in nonsmoking groups (P < 0.001). CONCLUSION: Smoking and snoring among adults aged over 30 years had correlation in our city.

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