A site-resolved two-dimensional quantum simulator with hundreds of trapped ions.

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation1. As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap2-4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap5,6. However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms7,8 using 2D ion trap quantum simulators.

Cytomegalovirus Infection and Alzheimer's Disease: A Meta-Analysis.

BACKGROUND: Evidence on the association of cytomegalovirus (CMV) infection with Alzheimer's disease (AD) is scarce and the results are inconsistent. OBJECTIVE: To investigate the association of CMV infection with the risk of AD. METHODS: Observational studies on the relationship between CMV infection and AD were identified from PubMed, Embase, Web of Science, and the Cochrane Library until September 30, 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effect meta-analysis was performed using a generic inverse-variance method, followed by sensitivity analyses and subgroup analyses based on study designs, regions, adjustments, and population types. RESULTS: Our search yielded 870 articles, of which 200 were duplicates and 663 did not meet the inclusion criteria, and finally yielded seven studies with 6,772 participants. No strong evidence was observed in the summary analysis for the association of CMV infection and risk of AD (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 0.88, 2.03, I2 =69.9%). However, subgroup analysis showed that an increased risk of AD was detected in East Asians (OR = 2.39; 95% CI: 1.63, 3.50, I2 = 0.00%), cohort studies (OR = 1.99; 95% CI: 1.35, 2.94, I2 = 28.20%), and studies with confounder adjustment (OR = 2.05; 95% CI: 1.52, 2.77, I2 = 0.00%). CONCLUSIONS: This meta-analysis provides evidence to support the heterogeneity of the associations between CMV infection and AD. Future studies with larger sample sizes and multi-ethnic populations are necessary.

Identification of supraoptimal temperatures in juvenile blueback herring (Alosa aestivalis) using survival, growth rate and scaled energy reserves.

For young fishes, growth of somatic tissues and energy reserves are critical steps for survival and progressing to subsequent life stages. When thermal regimes become supraoptimal, routine metabolic rates increase and leave less energy for young fish to maintain fitness-based activities and, in the case of anadromous fishes, less energy to prepare for emigration to coastal habitats. Thus, understanding how energy allocation strategies are affected by thermal regimes in young anadromous fish will help to inform climate-ready management of vulnerable species and their habitat. Blueback herring (Alosa aestivalis) are an anadromous fish species that remain at historically low population levels and are undergoing southern edge-range contraction, possibly due to climate change. We examined the effects of temperature (21°C, 24°C, 27°C, 30°C, 33°C) on survival, growth rate and energy reserves of juveniles collected from the mid-geographic range of the species. We identified a strong negative relationship between temperature and growth rate, resulting in smaller juveniles at high temperatures. We observed reduced survival at both 21°C and 33°C, increased fat and lean mass-at-length at high temperatures, but no difference in energy density. Juveniles were both smaller and contained greater scaled energy reserves at higher temperatures, indicating growth in length is more sensitive to temperature than growth of energy reserves. Currently, mid-geographic range juvenile blueback herring populations may be well suited for local thermal regimes, but continued warming could decrease survival and growth rates. Blueback herring populations may benefit from mitigation actions that maximize juvenile energy resources by increasing the availability of cold refugia and food-rich habitats, as well as reducing other stressors such as hypoxic zones.

Direct and size-mediated effects of temperature and ration-dependent growth rates on energy reserves in juvenile anadromous alewives (Alosa pseudoharengus).

Growth rate and energy reserves are important determinants of fitness and are governed by endogenous and exogenous factors. Thus, examining the influence of individual and multiple stressors on growth and energy reserves can help estimate population health under current and future conditions. In young anadromous fishes, freshwater habitat quality determines physiological state and fitness of juveniles emigrating to marine habitats. In this study, the authors tested how temperature and food availability affect survival, growth and energy reserves in juvenile anadromous alewives (Alosa pseudoharengus), a forage fish distributed along the eastern North American continent. Field-collected juvenile anadromous A. pseudoharengus were exposed for 21 days to one of two temperatures (21°C and 25°C) and one of two levels of food rations (1% or 2% tank biomass daily) and compared for differences in final size, fat mass-at-length, lean mass-at-length and energy density. Increased temperature and reduced ration both led to lower growth rates, and the effect of reduced ration was greater at higher temperature. Fat mass-at-length decreased with dry mass, and energy density increased with total length, suggesting size-based endogenous influences on energy reserves. Lower ration also directly decreased fat mass-at-length, lean mass-at-length and energy density. Given the fitness implications of size and energy reserves, temperature and food availability should be considered important indicators of nursery habitat quality and incorporated in A. pseudoharengus life-history models to improve forecasting of population health under climate change.

The decreased circular RNA hsa_circ_0072309 promotes cell apoptosis of ischemic stroke by sponging miR-100.

OBJECTIVE: To investigate the expression of circ_0072309 in patients with ischemic stroke (IS) and in LIFR humanized mice with middle cerebral artery occlusion (MCAO). Further, we explored the underlying mechanism of circ-0072309 in IS. MATERIALS AND METHODS: The content of circ-0072309 in serum of patients with IS (n = 70) was measured by qRT-PCR, and the ROC curve was analyzed. LIFR humanized mice were used to measure the content of circ-0072309 in ischemic hemisphere by qRT-PCR and the protein expression of cleaved-caspase-3, cleaved-caspase-8 were detected by Western blot. After that, the expression of miR-100 in serum of patients with IS and in ischemic hemisphere of MCAO mice were detected, and then, we analyzed the correlation between the expression of circ-0072309 and miR-100. The binding sites between circ-0072309 and miR-100 were predicted by online database. We detected whether cric-0072309 bind to miR-100 by Dual-Luciferase report in bEnd2. In addition, bEnd2 was treated with oxygen-glucose deprivation (OGD) to simulate injury of cerebral vascular after cerebral ischemia. After treated with miR-100 mimic or miR-100-inhibitor, we detected the cell survival and rate of cell apoptosis, and the content of cleaved-caspase-3 and caspase-8 protein. The target mRNA of miR-100 was predicted by bioinformatics analysis and analyzed by Dual-Luciferase. After treating bEnd2 with circ-0072309 and miR-100 mimic, we analyzed the cell survival and apoptosis to identify the potential regulatory mechanism. RESULTS: The results of qRT-PCR showed that the expression of circ-0072309 was significantly decreased while the content of miR-100 was significantly increased in the serum of IS patients and in the ischemic hemisphere of MCAO mice. There was a negative correlation between the expression of circ-0072309 and miR-100. The results of Dual-Luciferase showed that circ-0072309 could directly bind to miR-100. After treating bEnd2 with OGD, miR-100-mimic caused a decrease rate of cell survival and an increased rate of apoptosis. Dual-Luciferase showed that miR-100 regulated cell survival and apoptosis by directly binding to mTOR. By comparing treated bEnd2 with circ-0072309, co-transfected bEnd2 with circ-0072309 and miR-100 reduced cell survival and increased apoptosis. CONCLUSIONS: According to these results, this study revealed that the circ_0072309-miR-100-mTOR regulatory axis could alleviate IS, and it may be a potential target for the treatment of IS.

Response of AMP-activated protein kinase and lactate metabolism of largemouth bass (Micropterus salmoides) under acute hypoxic stress.

To study adaptation of largemouth bass (Micropterus salmoides) to hypoxic stress, we investigated physiological responses and lactate metabolism of the fish under acute hypoxia. The objectives of this study were to (a) observe changes in glucose, glycogen, and lactate content; (b) detect the activity of lactate dehydrogenase (LDH) in serum, brain, heart, and liver tissues; and (c) quantify the dynamic gene expression of AMP activated protein kinase alpha (AMPKα), hypoxia-inducible factor-1 alpha (HIF-1α), monocarboxylate transporter 1 (MCT1), monocarboxylate transporter 4 (MCT4), and lactate dehydrogenase-a (LDHa) following exposure to hypoxia. The fish were subjected to two hypoxia stresses (dissolved oxygen [DO] 1.20 ±â€¯0.2 mg/L and 3.50 ±â€¯0.3 mg/L, respectively) for 24 h. Our results showed that hypoxic stress significantly increased the decomposition of liver glycogen and significantly increased the concentration of blood glucose; however, the muscle glycogen content was not significantly decreased, which indicates that liver glycogen was the main energy source under acute hypoxia. Moreover, hypoxia led to accumulation of a large amount of lactic acid in tissues, possibly due to the activity of lactic acid dehydrogenase, but this process was delayed in the heart and brain relative to the liver. Additionally, hypoxia induced the expression of AMPKα, HIF-1α, MCT1, MCT4, and LDHa, suggesting that glycometabolism had switched from aerobic to anaerobic. Our results contribute to a better understanding of the molecular mechanisms of the response to hypoxia in largemouth bass.

Experimental Realization of Robust Geometric Quantum Gates with Solid-State Spins.

We experimentally realize a universal set of single-bit and two-bit geometric quantum gates by adiabatically controlling solid-state spins in a diamond defect. Compared with the nonadiabatic approach, the adiabatic scheme for geometric quantum computation offers a unique advantage of inherent robustness to parameter variations, which is explicitly demonstrated in our experiment by showing that the single-bit gates remain unchanged when the driving field amplitude varies by a factor of 2 or the detuning fluctuates in a range comparable to the inverse of the gate time. The reported adiabatic control technique and its convenient implementation offer a paradigm for achieving quantum computation through robust geometric quantum gates, which is important for quantum information systems with parameter-fluctuation noise such as those from the inhomogeneous coupling or the spectral diffusion.

Validation of the AJCC 8th prognostic system for breast cancer in an Asian healthcare setting.

AIMS: We aim to validate the AJCC 8th edition prognostic staging system for breast cancer in an Asian setting. METHODS: Clinico-pathologic information and cancer-specific survival (CSS) outcomes of 6287 stage I to III patients with invasive breast cancer who underwent upfront surgery at SingHealth institutions in Singapore from 2006 to 2014 were analyzed. Survival distributions for the different staging systems were estimated by the Kaplan-Meier method and compared using the log-rank tests. Multivariable Cox proportional hazards models were used, with Akaike Information Criterion (AIC) and Harrell's Concordance Index (C-index) to compare both staging systems. Among patients with positive hormone-receptor status, 84.8% received endocrine therapy. Among the cohort, 60.3% of received chemotherapy; 82.1% of node positive patients received chemotherapy and 86.0% of HER2-enriched patients in whom chemotherapy was also indicated received adjuvant HER2-targeted therapy. Ninety-seven percent of patients received anthracyclines and/or taxanes containing chemotherapy regime. RESULTS: The median follow up was 64 months. 2921 patients (46.5%) were discordant between the anatomic and prognostic systems of which 363 (5.8%) were upstaged and 2558 (40.7%) were down-staged. For all patients, stages in both the prognostic and anatomic systems were discriminating for 5-year CSS. Controlling for age, ethnicity and receipt of chemotherapy, the prognostic staging system model (AIC = 7538.87, C = 0.79) presented slightly better explanation and concordance of survival times than the anatomic staging system model (AIC = 7607.31, C = 0.77). CONCLUSION: The prognostic staging system was better than the anatomic staging system in predicting outcomes but the anatomic system remains relevant due to its ease of use.

Larval abundances of rockfishes that were historically targeted by fishing increased over 16 years in association with a large marine protected area.

Marine protected areas (MPAs) can facilitate recovery of diminished stocks by protecting reproductive adults. To effectively augment fisheries, however, reproductive output must increase within the bounds of MPAs so that larvae can be exported to surrounding areas and seed the region. In response to dramatic declines of rockfishes (Sebastes spp.) in southern California by the late 1990s two large MPAs, the Cowcod Conservation Areas (CCAs), were established in 2001. To evaluate whether the CCAs affected rockfish productivity we evaluated the dynamics of 8 species that were, and 7 that were not, historically targeted by fishing. Abundances of 6/8 targeted and 4/7 non-targeted species increased regionally from 1998 to 2013. These upturns were probably affected by environmental conditions in addition to changes in fishing pressure as the presence of most species correlated negatively with temperature, and temperature was lower than the historic average in 11/15 years. Seventy-five per cent of the targeted, but none of the non-targeted species increased at a greater rate inside than outside the CCAs while controlling for environmental factors. Results indicate that management actions, coupled with favourable environmental conditions, facilitated the resurgence of multiple rockfish species that were targeted by intense fishing effort for decades.

Perinatal exposure to 2,2',4'4' -Tetrabromodiphenyl ether induces testicular toxicity in adult rats.

Since 1965, polybrominated diphenyl ethers (PBDEs) have been used internationally as flame-retardant additives. PBDEs were recently withdrawn from commerce in North America and Europe due to their environmental persistence, bioaccumulative properties and endocrine-disrupting effects. Generations exposed perinatally to the highest environmental doses of PBDE account for one-fifth of the total United States population. While, toxicity of PBDE for the male reproductive system has been demonstrated in several human and animal studies, the long-lasting effects of perinatal exposures on male reproduction are still poorly understood. In this study, pregnant Wistar rats were exposed to 0.2mg/kg 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) from gestation day 8 until postnatal day 21. Male reproductive outcomes were analyzed on postnatal day 120 in offspring. Exposed animals had significantly smaller testes, displayed decreased sperm production per testis weight, had significantly increased percentage of morphologically abnormal spermatozoa, and showed an increase in spermatozoa head size. Perinatal BDE-47 exposure led to significant changes in testes transcriptome, including suppression of genes essential for spermatogenesis and activation of immune response genes. In particular, we observed a 4-fold average decrease in expression of protamine and transition protein genes in testes, suggesting that histone-protamine exchange may be dysregulated during spermatogenesis, resulting in an aberrant sperm epigenome. The possibility of long-lasting effects of developmental PBDE exposures calls for additional studies to build a foundation for the development of preventive and protective interventions against the environmentally-induced decline in fertility.

Analysis of bromocriptine treatment in pregnant pituitary prolactinoma patients.

OBJECTIVE: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma. MATERIALS AND METHODS: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine. RESULTS: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05). CONCLUSION: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

[The value and comparison of plasma adrenocorticotropic hormone and urinary free cortisol in predicting long-term outcome after operation of Cushing's disease].

Objective: To study and the value of morning plasma adrenocorticotropic hormone (ACTH) and urinary free cortisol (24 h UFC) within 3 days after operation in patients with Cushing's disease in predicting the long-term outcome. Methods: The clinical data of 140 patients with Cushing's disease who were treated in Department of Neurosurgery of PUMCH from 2012 to 2014 were analyzed retrospectively.The univariate analysis, multivariate Logistic analysis, ROC curve analysis and other statistical methods were used to study the predicting value of morning plasma ACTH and 24 h UFC in 3 days post operation. Results: Univariate analysis showed that in the two groups of the early remission and no remission, there was significant statistical difference between the preoperative ACTH, preoperative 24 h UFC, postoperative ACTH and postoperative 24 h UFC (P<0.05, <0.01, <0.01). Logistic analysis showed that ACTH and 24 h UFC after operation of two groups had significant difference (P<0.01, <0.05). ROC curve analysis showed that postoperative cutoff values of ACTH and 24 h UFC were 4.11 pmol/L (18.7 pg/ml) and 281.42 nmol (102 µg)/24 h. ROC analysis was performed to evaluate the predicting performance of postoperative ACTH, resulting in an area under the curve (AUC) of 0.917 (95%CI: 0.858-0.957, P<0.01). In comparison, 24 h UFC had an AUC of 0.814 (95%CI: 0.739-0.875, P<0.01). The predicting value of ACTH is significantly better than that of 24 h UFC (P=0.005). Conclusion: Early morning 24 h UFC and ACTH within 3 days after operation both showed considerable accuracy in predicting the long-term outcome of Cushing's disease, and the significance of ACTH was even greater than that of 24 h UFC.

[Surgical treatment of pituitary adenomas in childhood and adolescence].

Objective: To investigate the clinical characteristics and treatment of pituitary adenomas of childhood and adolescence. Methods: Thisarticle was a retrospective study of 140 pituitary adenomas of childhood and adolescence that was admitted into Peking Union Medical College Hospital from December 1987 to December 2014, whose clinical manifestations, hormone secretions, images, pathological types, surgical complications and follow-ups were studied. Results: A total of 58 (41.4%) males and 82 females (58.6%) were included, whose mean age was 12.5 years old (age range from 7 to 18). As for the type of tumors, ACTH adenoma, PRL adenoma, GH adenoma, non-functional adenoma and multiple-secreting adenoma accounted for 35.7%, 25.7%, 12.2%, 25.7% and 0.7%, respectively. Microadenoma accounted for 33.6% of total patients, while macroadenoma and giant adenoma accounted for 60.0% and 6.4% respectively. 19.3% of adenomas in our study wereinvasive. Transsphenoidal approach surgery was commonly used and accounted for 97.9% of cases in our study, 2 of which used intraoperative navigation assistance. Total resection was achieved in 93.6% of patients, and the rest achieved subtotal resection. 108 (77.1%) patients got full term follow-up until 1 year after surgery, and tumor recurred in 14 patients (13.0%). Conclusions: ACTH-secreting adenoma is the most common pituitary adenoma in childhood and adolescence which need surgical treatment. Transsphenoidal approach surgery is the most commonly used surgical procedure. The recurrence rate is about 13%, and the patients need regular examination of pituitary hormones and image study to confirm the recurrence.

[Use early morning serum cortisollevel to evaluate the effect of Cushing's disease after transsphenoidal surgery].

OBJECTIVE: To predict the therapeutic effect of Cushing's disease after transsphenoidal surgery by using morning serum cortisol level. METHODS: The clinical data of 275 cases that had transsphenoidal surgery in Peking Union Medical College Hospital from 2010 to 2014 were analyzed retrospectively.Early morning serum cortisol level less than 140 nmol/L 3 days postoperation was usedto predict endocrinological remission. And long-term efficacy was evaluated by follow-up. RESULTS: Of the 275 patients, there were 49 males and 226 females; average age was 36.5 years old.Remission wasconfirmed in 201 cases, the remission rate was 73.1%, and 8 cases recurrent duringfollow-up.There were 17 macroadenomas, theremission rate was 47.1%; 258 microadenomas and MRI negative adenomas, the remission rate was 74.8%.And 43 recurrent cases had reoperations; the remission rate was 46.5%. CONCLUSION: Early morningserum cortisol 3 days post operation can evaluate the effectof transsphenoidal surgery, but even if the level of cortisol is less than 140 nmol/L, there is still tumor recurrence.Patients should be follow-up for a lifetime.

[Analysis of curative effect of surgical therapy for male prolactinoma].

OBJECTIVE: To summarize the treatment outcome of surgery for male prolactinoma. METHODS: One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach. RESULTS: Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index≤3 (P<0.01). CONCLUSION: Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index.

[Analysis of outcomes and learning curve of endoscopic transsphenoidal surgeries for 124 patients with pituitary adenomas].

OBJECTIVE: To investigate the outcomes of the Endoscopic transsphenoidal surgery for patients with pituitary adenomas, analyze the learning curve and provide reference for future surgeries. METHODS: Retrospective analysis was carried out on 124 patients by endoscopic transsphenoidal surgery with a single neurosurgeon over a period spanning from January 2010 to January 2014 at Peking Union Medical College Hospital.The changes of endocrine and tumor imaging before and after surgery were analysed. Operative time and complication rates of one surgeon in the early period of learning curve were compared with that in later period. RESULTS: There were significant differences in Gross total resection (GTR) rate of pituitary adenomas with different sizes and different Knosp classifications (P<0.01, P<0.01). GTR rate of huge adenomas was significantly lower than that of macroadenoma and adenomas (P<0.05). GTR rate of Knosp 4 grade adenoma was significantly lower than that of Knosp 0-3 level (P<0.05). No significant difference in GTR among all types of functional pituitary adenomas and hormone levels after surgery was observed (P>0.05). In addition, no significant difference (P>0.05) in complications among different sizes, Knosp grade and type of pituitary adenomas was observed.GTR of Knosp 4 adenoma in later period of the learning curve was significantly higher than that in early period (P<0.05). Meanwhile the operative time was significantly lower than early period (P<0.05). CONCLUSIONS: Endoscopic transsphenoidal pituitary adenoma resection has the advantages of wider surgical field, higher GTR rate, less trauma, fewer complications and better life quality of patients.Through standardized learning, the GTR rate of the invasive pituitary adenomas can be improved.

Neuropeptide Y mediates glucocorticoid-induced osteoporosis and marrow adiposity in mice.

UNLABELLED: Increased neuropeptide Y (NPY) expression occurred in the glucocorticoid-induced osteoporotic skeleton. NPY knockout mice exhibited a minor response to the glucocorticoid-mediated exacerbation of bone accretion and fatty marrow pathogenesis. NPY deletion restored SITR1 signaling and enhanced PPARγ ubiquitination of bone tissue, an alternative strategy for ameliorating glucocorticoid-induced skeletal deterioration. INTRODUCTION: Glucocorticoid excess is observed to worsen the pathogenesis of osteoporosis and fatty marrow. This study was undertaken to investigate the contribution of neuropeptide Y (NPY) to glucocorticoid-induced bone loss and marrow adiposity. METHODS: NPY knockout and wild-type mice were administered methylprednisolone for four consecutive weeks. Bone mineral density, microarchitecture, and calcein-labeled mineral acquisition were quantified by µCT, dual energy X-ray absorptiometry, and histomorphometry. Expression of osteogenic and adipogenic markers and acetylation states of PPARγ were detected by RT-quantitative PCR, immunoprecipitation, and immunoblotting. RESULTS: High NPY levels were associated with glucocorticoid-induced trabecular bone deterioration and marrow fat accumulation. Mice lacking NPY had high bone mass concomitant with spacious trabecular and cortical bone microstructure. NPY deletion shielded skeletal tissues from the glucocorticoid-induced impediment of bone mass, trabecular morphometric characteristics, mineral accretion activity, and fatty marrow development. Ex vivo, NPY deficiency sustained osteogenic differentiation capacity and curtailed the glucocorticoid-mediated escalation of adipocyte formation reactions of primary bone-marrow mesenchymal cells. NPY deletion appeared to modulate Y1 and Y2 receptors, sirtuin 1, ERK, and p38 signaling pathways, an effect that facilitated hypoacetylation and ubiquitination of adipogenic transcription factor PPARγ in the skeletal tissues exposed to glucocorticoid stress. CONCLUSIONS: NPY mediates the glucocorticoid-induced disturbance of mineral accretion and marrow adipogenesis through post-translational modification of PPARγ. This study brings a new molecular insight into the disintegration of adipogenic and osteogenic activities within glucocorticoid-mediated osteoporotic skeletons. Control of NPY is an alternative strategy to ameliorate glucocorticoid-induced bone destruction and fatty marrow.

[The surgery of thyrotropin-secreting pituitary adenomas and the significance of thyroid stimulating hormone level in follow-up].

Objective: To explore the clinical characteristics of thyrotropin-secreting pituitary adenomas and the effect of the transsphenoidal approach of procedure with/without drug treatment for thyrotropin-secreting pituitary adenomas, and to investigate the correlation between the prognosis of thyrotropin-secreting pituitary adenomas and the postoperative level of thyroid stimulating hormone (TSH). Methods: A total of 45 patients with thyrotropin-secreting pituitary adenoma who hospitalized in Peking Union Medical College Hospital from 2000 to 2015 were enrolled in the study.We collected the clinical features, hormone levels, imaging findings, treatment and follow-up data of these patients. Results: The average age of the patients was 40.26 years old and the average disease duration was 5.83 years.Among them, 8 cases were microadenomas and 37 cases were macroadenoma.Thirty patients were treated with somatostatin analogues before surgery.TSH level was significantly decreased after operation (P=0.012). All of them had done the pituitary surgery, including 44 transsphenoidal surgery and 1 subfrontal surgery that had recurrence one year after the transsphenoidal surgery.The TSH level of 34 cases went back to normal on the third day after surgery.The remission rates on three months and one year after surgery in patients with TSH level<0.1 mIU/L on postoperative day (POD) 3 were significantly higher than those in patients with TSH level>0.1 mIU/L on POD3.As well as the remission rates on three months and one year after surgery in patients with TSH level normal on postoperative one month were significantly higher than those in patients with TSH level abnormal on postoperative one month. Conclusions: TSH level of postoperative one month could be used to predict prognosis and monitor recurrence.