Extracellular vesicles in bone and tooth: A state-of-art paradigm in skeletal regeneration.

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.

Association Between Psoriasis and Erectile Dysfunction: A Meta-Analysis.

BACKGROUND: Several studies have shown a relationship between psoriasis and erectile dysfunction (ED), but a meta-analysis of the data has not been performed. AIM: To conduct a comprehensive meta-analysis of existing evidence to quantify and compare the risk of ED with psoriasis. METHODS: A systematic literature search was conducted using MEDLINE, EMBASE, Cochrane databases, and Google Scholar. We calculated pooled odds ratios (OR), standardized mean difference (SMD), and 95% CI. OUTCOMES: Outcome measures included characteristics of included studies, association between psoriasis and ED risk, and association for adjusted-for-covariates studies between psoriasis and ED risk. RESULTS: In total, 9 studies with 36,242 psoriasis patients and 1,657,711 controls (participants without psoriasis) met inclusion criteria and showed that there was statistically significant association between psoriasis and ED risk (OR 1.35; 95% CI 1.29-1.41; P < .00001; I2 = 44%). A significant association for adjusted-for-covariates studies between psoriasis and ED risk was also observed (OR 1.22; 95% CI 1.08-1.37; P = .002; I2 = 43.8%). It revealed the International Index of Erectile Function-5 score was statistically significantly lower in the psoriasis group than controls (SMD -3.09; 95% CI -4.81 to -1.37; P = .0004; I2 = 77%). A subgroup analysis was performed to potentially explain heterogeneity. It examined the main potential sources of inter-study variance including variance sample sizes and different assessment tools for ED. CLINICAL TRANSLATION: The risk of ED in psoriasis patients should also be assessed by physicians. CONCLUSIONS: This study is a well-designed and comprehensive meta-analysis to examine the relationship between psoriasis and risk of ED. However, the included studies are mostly cross-sectional or have small sample cohorts, which could bring bias and heterogeneity into the analysis. Our findings support the hypothesis that psoriasis is associated with an increased risk of ED. Furthermore, additional prospective cohort studies are needed to elucidate these relationships and to advance knowledge in this field. Wu T, Duan X, Chen S, et al. Association Between Psoriasis and Erectile Dysfunction: A Meta-analysis. J Sex Med 2018;15:839-847.

The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy.

BACKGROUND/AIMS: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. METHODS: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n =6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. RESULTS: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. CONCLUSIONS: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology.

An empirical study on the asset-light operation and corporate performance of China's tourism listed companies.

Transitioning to an asset-light strategy is a significant shift for tourism companies in light of the global COVID-19 outbreak. This study investigates the impact of asset-light strategy on corporate performance using a sample of 588 firm-year observations from China A-share publicly traded tourism companies from 2003 to 2021. Using two-way fixed effects models, our results indicate that adopting an asset-light strategy can significantly improve the performance of tourism enterprises. We further verify that this influence mechanism is supply chain management using path analysis. More interestingly, the positive impact of asset-light strategy on enterprise performance is particularly significant in non-state-owned enterprises. Robustness tests with the system GMM method, the variable substitution method and the two-stage instrumental variables method support our main findings. The findings have significant ramifications for assisting the tourism industry, managers, and investors to strategically cope with settings that are complex and dynamic.

A systematic review and meta-analysis of the association between psoriasis and hypertension with adjustment for covariates.

BACKGROUND: Several studies have shown a relationship between psoriasis and hypertension, but no meta-analysis has been restricted to studies that adjusted for confounders. The aim of the study was to estimate the association between psoriasis and hypertension with adjustment for covariates. METHODS: A systematic literature search in the MEDLINE, Embase, Cochrane databases, and Google Scholar was conducted to identify relevant studies which reported the association of psoriasis with the risk of hypertension published up to November 2018 in English. Data analysis was performed with Stata V.12, and Begg adjusted rank correlation test and Egger regression asymmetry test were used to detect publication bias. RESULTS: A total of 16 adjusted-for-covariates studies, involving 50,291 cases with hypertension in 255,132 psoriasis patients and 76,547 cases with hypertension in 814,631 controls (no psoriasis), were included in this meta-analysis. The results indicated that psoriasis was associated with an increased risk of hypertension compared to those without psoriasis, and the prevalence of hypertension in severe psoriasis patients was higher than that in mild psoriasis patients, and the risk of hypertension in psoriasis patients was higher than that in nonpsoriasis patients in Europe and Asia. CONCLUSION: We conducted this meta-analysis using the adjusted-for-covariates odds ratio, demonstrating that psoriasis was associated with an increased risk of hypertension compared to those without psoriasis.

Attributable risk of all-cause mortality in hypertensive adults based on disease risk prediction model: A Chinese cohort study.

BACKGROUND: The aim of this study was to estimate the attributable risk for all-cause mortality in hypertensive adults living in Beijing, China. METHODS: We conducted a prospective cohort study on the basis of the disease risk prediction model, which included 3006 hypertensive patients aged 50 and over who participated in the annual health examination from thirty-eight community health centers were randomly selected from all 53 community health centers in Dongcheng district of Beijing in China. This cohort study was conducted from January 1, 2013 to June 31, 2018 in these community health centers. Data included age, gender, education level, BMI, smoking and drinking status, renal function, diabetes mellitus (DM), coronary heart disease, levels of blood pressure, use of medications, and blood lipid levels. RESULTS: the follow-up time was 4.90±0.51 years. There were significant survival differences by gender, renal function (eGFR>90 vs. 60-90 vs. <60mL/min per 1.73m2), smoking (smoking vs. No smoking), hypertension severity (SBP≥140 or DBP≥r vs. SBP/DBP<140/90mmHg), education level (<6 vs. 6-12 vs. >12 years), coronary heart disease (CHD) (CHD vs. NO CHD). In the multivariate Cox proportional hazard analysis, the prognostic factors of all-cause mortality in hypertensive patients were male [HR 1.662, 95% CI 1.110-2.489, p=0.014], educational level<6 years [HR 2.044, 95% CI 1.164-3.591, p 0.013], age ≥65 years [HR 3.092, 95% CI 1.717-5.571, p<0.001], smoking [HR 1.885, 95% CI 1.170-3.309, p=0.009], eGFR<60mL/min per 1.73m2 [HR 3.591, 95% CI 2.023-6.371, p<0.001]. CONCLUSIONS: we conclude that decreasing eGFR, increasing age, smoking, low education and gender (male) are significant and independent risk factor for mortality in hypertension for this urban cohort. Recommendations may include protecting renal function, providing patient education, and cessation of smoking. It highlights that early preventive measures are needed to detect kidney impairment and protect renal function. It also suggests that earlier smoking cessation may be important for hypertensive patients.

Neoadjuvant chemotherapy before radical prostatectomy for locally advanced prostate cancer: Protocol for a systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of neoadjuvant chemotherapy (NAC) for locally advance prostate patients undergoing radical prostatectomy. METHODS: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion and exclusion flow charts will be conducted according to PRISMA guidelines. The identified reports will be critically appraised using GRADE approach. Bias and heterogeneity of included studies will be assessed, and outcome measurements from individual studies will be combined with 95% confidence interval using a fixed- or random-effects model if qualified. RESULTS: This study will provide evidence and data on the tolerance and efficacy of NAC followed by radical prostatectomy (RP). CONCLUSION: The application of taxanes-based chemotherapy has been widened to metastatic hormone sensitive prostate cancer in recent years. To be more vigorous, whether neoadjuvant administration of these cytotoxic agents can improve the outcome of RP in locally advance prostate cancer patients has been explored. This study aims to synthesis data regarding the adverse effect, response rate, recurrence, and survival from multiple trials, and to guide the healthcare practitioners using an evidence-based approach.

Surveillance of non-muscle invasive bladder cancer using fluorescence in situ hybridization: Protocol for a systematic review and meta-analysis.

BACKGROUND: To evaluate the diagnostic effectiveness and predictive value of fluorescence in situ hybridization (FISH) in the surveillance of non-muscle invasive bladder cancer (NMIBC). METHODS: PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, and Cochrane Library will be searched for studies related to the topic. The identification, inclusion, and exclusion flowcharts will be conducted according to preferred reporting items for systematic reviews and meta-analysis guidelines. The identified reports will be critically appraised according to the Newcastle-Ottawa scale, quality assessment of diagnostic accuracy studies-2 and standards for reporting of diagnostic accuracy 2015. Forest plots will be generated to display hazard ratios, sensitivities, and specificities. Pooled estimates with their 95% confidence intervals will be calculated using the bivariate model, the hierarchical summary receiver operating characteristic model and a fixed- or random-effects model. RESULTS: This study will provide evidence and data to form a comprehensive understanding of the value of FISH in the surveillance of NMIBC. CONCLUSION: The diagnostic efficacy of FISH will be affected by post-therapy factors. However, FISH still could facilitate the surveillance of NMIBC owing to its non-invasive feature. This study will improve the clinical decision-making and enlighten the future research of NMIBC.

New combination strategy of photodynamic therapy and surgery in treating recurrent basal cell carcinoma, a case report.

BACKGROUND: Surgery is considered the most effective treatment for basal cell carcinoma because it permits the analysis of surgical margins following excision. However, even Mohs surgery isn't desirable for predictable aggressive tumor. Treatment of recurrent basal cell carcinoma can be challenging. METHODS: This case study is on a patient with a recurrent basal cell caricinoma on his zygomatic region. Since the tumor showed a suspected bone invasion, surgical excision of the tumor alone was problematic. Hence a one-time photodynamic therapy was performed in the basal segment of the defect. RESULTS: No recurrence was detected at the patient's 1-year follow-up visit. CONCLUSIONS: The tumor was successfully treated by combing surgery with photodynamic therapy. This treatment combination can be adopted as a new strategy in the study and treatment of recurrent basal cell carcinoma cases.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

RATIONALE: Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. PATIENT CONCERNS: This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. DIAGNOSES: Examinations revealed pituitary thyrotropin-secreting macroadenoma. INTERVENTIONS: We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. OUTCOMES: This patient successfully fathered a child. LESSONS: To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma.

Potentials of combining nanomaterials and stem cell therapy in myocardial repair.

Cardiac diseases have become the leading cause of death worldwide. Developing efficient strategies to treat such diseases is of great urgency. Stem cell-based regeneration medicine offers a novel approach for heart repair. However, low retention and poor survival rate of engrafted cells limit its applications. Nanomaterials have shown great potentials in addressing above issues due to nanoparticles-bio interactions. Therefore, combining nanomaterials and stem cell therapy is of great interest and significance for heart repair. Herein, we provide a comprehensive understanding of the applications of four types of nanomaterials (nanogels, polymeric nanomaterials, inorganic nanomaterials and exosomes) in stem cell therapy for myocardial repair. In addition, we launch an initial discussion on current problems and more importantly, possible solutions for myocardial repair.

Case report of recurrent atrial fibrillation induced by thyrotropin-secreting pituitary adenoma with Graves' disease.

RATIONALE: Thyrotropin-secreting adenoma (TSHoma) is rare. Even though the thyrotoxicosis is mild in patients with TSHoma, it is still a rare cause of arrhythmia, ignore of mild disfunction of thyroid function of TSHoma can lead to the delayed diagnosis of pituitary tumor or leading to recurring of complications. Graves' disease is an auto-immue endocrinological disorder. Association of TSHoma and Graves's disease is extremely rare. Coexistence of these two diseases made the diagnosis and treatment complicated. PATIENT CONCERNS: This patient was a 55-year-old man who had been referred to the department of endocrinology and metabolism of the West China Hospital due to recurrent atrial fibrillation (AF) and thyroxicosis. DIAGNOSES: Examinations revealed pituitary thyrotropin-secreting macroadenoma with Graves' disease. INTERVENTIONS: We conducted transsphenoidal surgery. Thyrozol was used to treat the recurrence of Graves' disease after pituitary surgery. OUTCOMES: The TSHoma was successfully cured, and recurrent Graves' disease was controlled very well. LESSONS: The association of TSHoma and Graves' disease is extremely rare. Even though the clinical features of thyrotoxicosis are milder in patients with TSHoma, thyroid function tests are still important clinical assessment of patients with AF, which is an arrhythmia associated with hyperthyroidism. TSHoma is a rare cause of thyrotoxicosis; however, ignoring of the mild disfunction caused by TSHoma can lead to the delayed diagnosis of pituitary tumors or to recurring of complications of TSHoma.

A comprehensive comparison of fluorescence in situ hybridization and cytology for the detection of upper urinary tract urothelial carcinoma: A systematic review and meta-analysis.

OBJECTIVE: To compare the relative effectiveness of fluorescence in situ hybridization (FISH) and cytology in diagnosing upper urinary tract urothelial carcinoma (UUT-UC) and to evaluate the advantages and potential deficiencies of FISH analysis. METHODS: We performed a complete systematic review based on studies from PubMed/Medline, Embase, Web of Science, Ovid, Web of Knowledge, and Cochrane Library. We identified 2031 patients with strict criteria in 14 individual studies between January 2005 to November 2017 in accordance to preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines, we summarized the test performance using bivariate random effects models. RESULTS: FISH was superior to cytology in terms of pooled sensitivities (84.0%, 95% confidence interval [CI] 74.4-90.5% vs 40.0%, 95% CI 33.6-46.7%). FISH and cytology were similar to each other in terms of pooled specificities, which were 89.5% (95% CI 85.3-92.6%) for FISH and 95.9% (95% CI 91.2-98.1%) for cytology. CONCLUSION: We confirm the superiority of FISH over cytology in terms of sensitivity and find similar diagnostic outcomes between them based on systematic analysis. Therefore, we demonstrate that FISH is extremely sensitive while still very reliable with a relatively low error rate for diagnosing UUT-UC.

Insulin regulates astrocyte gliotransmission and modulates behavior.

Complications of diabetes affect tissues throughout the body, including the central nervous system. Epidemiological studies show that diabetic patients have an increased risk of depression, anxiety, age-related cognitive decline, and Alzheimer's disease. Mice lacking insulin receptor (IR) in the brain or on hypothalamic neurons display an array of metabolic abnormalities; however, the role of insulin action on astrocytes and neurobehaviors remains less well studied. Here, we demonstrate that astrocytes are a direct insulin target in the brain and that knockout of IR on astrocytes causes increased anxiety- and depressive-like behaviors in mice. This can be reproduced in part by deletion of IR on astrocytes in the nucleus accumbens. At a molecular level, loss of insulin signaling in astrocytes impaired tyrosine phosphorylation of Munc18c. This led to decreased exocytosis of ATP from astrocytes, resulting in decreased purinergic signaling on dopaminergic neurons. These reductions contributed to decreased dopamine release from brain slices. Central administration of ATP analogs could reverse depressive-like behaviors in mice with astrocyte IR knockout. Thus, astrocytic insulin signaling plays an important role in dopaminergic signaling, providing a potential mechanism by which astrocytic insulin action may contribute to increased rates of depression in people with diabetes, obesity, and other insulin-resistant states.

Treg depletion in non-human primates using a novel diphtheria toxin-based anti-human CCR4 immunotoxin.

Regulatory T cells (Treg) play an important role in modulating the immune response and has attracted increasing attention in diverse fields such as cancer treatment, transplantation and autoimmune diseases. CC chemokine receptor 4 (CCR4) is expressed on the majority of Tregs, especially on effector Tregs. Recently we have developed a diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4(+) cells in vivo. In this study, we demonstrated that the anti-human CCR4 immunotoxin bound and depleted monkey CCR4(+) cells in vitro. We also demonstrated that the immunotoxin bound to the CCR4(+)Foxp3(+) monkey Tregs in vitro. In vivo studies performed in two naive cynomolgus monkeys revealed 78-89% CCR4(+)Foxp3(+) Treg depletion in peripheral blood lasting approximately 10 days. In lymph nodes, 89-96% CCR4(+)Foxp3(+) Tregs were depleted. No effect was observed in other cell populations including CD8(+) T cells, other CD4(+) T cells, B cells and NK cells. To our knowledge, this is the first agent that effectively depleted non-human primate (NHP) Tregs. This immunotoxin has potential to deplete effector Tregs for combined cancer treatment.

Association between the PPARG gene polymorphism and the risk of diabetic nephropathy: a meta-analysis.

BACKGROUND: The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma (PPARG) gene is suggested to associate with diabetic nephropathy. AIM: A meta-analysis was conducted to investigate the potential association of PPARG gene polymorphisms with susceptibility to diabetic nephropathy. METHODS: A comprehensive search of MEDLINE (1966 to June 2011) was conducted to identify published epidemiologic studies related to polymorphisms of the PPARG gene and diabetic nephropathy. A database search yielded 5 studies involving 2758 patients. Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS: The combined results based on all studies showed no significant difference in genotype distribution (Pro/Pro: OR. 1.42, 95% CI, 0.96-2.09); Pro/Ala: OR, 0.74, 95% CI, 0.50-1.10; Ala/Ala: OR, 0.85, 95% CI, 0.52-1.38) between cases and controls. After stratification for race, results were similar except that patients with diabetic nephropathy had a significantly higher frequency of Pro/Pro (OR, 1.82; 95% CI, 1.17-2.85) than controls among Asians. CONCLUSION: This meta-analysis suggests that the Pro12Ala polymorphism of the PPARG gene may be associated with diabetic nephropathy among Asians.