Ncor1 Deficiency Promotes Osteoclastogenesis and Exacerbates Periodontitis.

Nuclear receptor corepressor 1 (Ncor1) has been reported to regulate different transcription factors in different biological processes, including metabolism, inflammation, and circadian rhythms. However, the role of Ncor1 in periodontitis has not been elucidated. The aims of the present study were to investigate the role of Ncor1 in experimental periodontitis and to explore the underlying mechanisms through an experimental periodontitis model in myeloid cell-specific Ncor1-deficient mice. Myeloid cell-specific Ncor1 knockout (MNKO) mice were generated, and experimental periodontitis induced by ligation using 5-0 silk sutures was established. Ncor1 flox/flox mice were used as littermate controls (LC). Histological staining and micro-computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. Flow cytometry was conducted to observe the effect of Ncor1 on myeloid cells. RNA sequencing was used to explore the differentially targeted genes in osteoclastogenesis in the absence of Ncor1. Coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) experiments, and dual luciferase assays were performed to explore the relationship between NCoR1 and the targeted gene. Alveolar bone resorption in the MNKO mice was significantly greater than that in the LC mice after periodontitis induction and osteoclastogenesis in vitro. The percentage of CD11b+ cells, particularly CD11b+ Ly6G+ neutrophils, was substantially higher in gingival tissues in the MNKO mice than in the LC mice. Results of RNA sequencing demonstrated that CCAAT enhancer binding protein α (Cebpα) was one of the most differentially expressed genes between the MNKO and LC groups. Mechanistically, Co-IP assays, ChIP experiments, and dual luciferase assays revealed that NCOR1 interacted with peroxisome proliferator-activated receptor gamma (PPARγ) and cooperated with HDAC3 to control the transcription of Cebpα. In conclusion, Ncor1 deficiency promoted osteoclast and neutrophil formation in mice with experimental periodontitis. It regulated the transcription of Cebpα via PPARγ to promote osteoclast differentiation.

The prognostic role of albumin-bilirubin grade in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

OBJECTIVE: Our aim was to explore the prognostic role of baseline albumin-bilirubin levels (ALBI) on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This retrospective study enrolled 58 cases of advanced NSCLC patients who received immune checkpoint inhibitor therapy from January 2019 to February 2022 in People's Hospital of Macheng. Patients were grouped according to the levels of baseline ALBI. The corresponding cut-off values ​​were determined by receiver operating characteristic (ROC) curves. We also assessed potential predictive models for predicting efficacy of immunotherapy in advanced NSCLC. RESULTS: The median overall survival (OS) was not reached. The median OS of patients with PS ≤ 1 after immunotherapy was significantly longer than that of PS ≥ 2, which was NR vs. 6.67 months (HR=0.14, 95% CI: 0.05-0.46; p<0.01). The risk of death for patients with low ALBI (<-2.52) was significantly lower than that of patients with high ALBI (HR=0.28, 95% CI: 0.08-0.94; p=0.03). Univariate analysis showed that baseline ALBI and PS were factors significantly affecting OS in patients with advanced NSCLC after immunotherapy (p<0.05 for all). The combination of ALBI and PS showed a good predictive value in prognosis of these patients after immunotherapy (p<0.01). CONCLUSIONS: The baseline ALBI and PS may serve as prognostic factors for advanced NSCLC patients treated with immunotherapy.

The real experience of patients after liver transplantation in intensive care unit.

ABSTRACT: We aimed to explore the real experience of patients after liver transplantation in the intensive care unit (ICU).Objective sampling method was used to select patients transferred to the ICU in 10 hospitals in Zhuhai from May 2018 to August 2020. Patients need liver transplantation due to advanced liver cancer and decompensated cirrhosis. The eligibility criteria of patients mainly included liver transplant patients who were clear-minded and willing to participate in the study and had stayed in ICU. Phenomenological research methods and in-depth interviews were used in this qualitative study.The results showed that the true experience of patients after liver transplantation during ICU stay was summarized into four themes. The strengths of our qualitative research are that we can find the trend from a phenomenon through interviews and other methods to provide a directional foundation for future quantitative research. Its limitations are that it requires a lot of manpower and time, and its objectivity and universality are limited.Hospitalization experience in the ICU may lead to many negative experiences for liver transplant patients. Nurses should fully understand and pay attention to the psychological changes in patients. Nurses should take effective targeted measures to reduce or eliminate patients' fear of ICU stay and promote rehabilitation.

[Mediating effect of milk intake between family socioeconomic status and body mass index of children and adolescents].

OBJECTIVE: To examine the association between family socioeconomic status (SES) and body mass index (BMI) z-score of children and adolescents, and the mediating effect of milk intake in this association. METHODS: In the study, 2 496 students and their parents were selected from 16 schools (4 urban middle schools, 4 rural middle schools, 4 urban primary schools, and 4 rural primary schools) using a stratified cluster sampling method. The frequency and amount of weekly milk intake from the 7-day Food Records reported by the students were extracted. The parents' education and household income were the indicators of family SES. The mediating effect of milk intake between family SES and BMI z-score of children and adolescents were tested using the PROCESS add-on SPSS software. RESULTS: Parents' education level and household income were positively correlated with BMI z-score of children and adolescents (P=0.001 and 0.038, respectively). The overall average daily intake of milk was (0.92±0.84) servings, and the frequency was (4.43±2.70) days per week. The students of primary school, in urban areas, with higher parents' education level, with higher household income, and being non-obese were likely to have higher frequency and amount of milk intake. Milk intake was one of the mediating factors in the relationship between family SES and BMI z-score of children and adolescents. Specifically, the mediating effect of the frequency of milk intake accounted for -6.57% and -10.21% of the total effects of the association between the parents' education and the household income with BMI z-score of children and adolescents, respectively. The mediating effect of the daily intake of milk accounted for -3.63% and -5.86% of the total effects of the association between the parents' education and the household income with BMI z-score of children and adolescents, respectively. CONCLUSION: The milk intake of Chinese children and adolescents still needs to be improved. High family SES was found to contribute to high BMI z-score, mediated by the milk intake which was the protective factors of BMI z-score. Further research is needed to study other dietary or physical exercise behaviors that mediate the relationship between family SES and BMI z-score of children and adolescents in order to adopt more targeted interventions.

[Analysis of family influencing factors of dietary behavior pattern of children and adolescents].

Objective: To identify dietary patterns among children and adolescents aged from 7 to 18 and the associations between these patterns and family characteristics. Methods: A stratified cluster sampling method was used. Data was collected on 2 438 students and their parents through physical examinations and questionnaires. Students were from 16 schools (4 urban primary schools, 4 rural primary schools, 4 urban middle schools, and 4 rural middle schools) in Fangshan district, Beijing. Dietary patterns were derived by factor analysis. Rank sum tests and Pearson correlation analysis were used to analyze the correlations between family characteristics and the scores on dietary patterns. Generalized linear mixed models were used to examine the associations between family characteristics and dietary patterns, for univariate analyses. Results: Two dietary patterns were identified: the risk pattern and the protective pattern. Results from the univariate analyses showed that maternal BMI was associated with the risk pattern (P=0.011). All factors, including the only-child, parental education level, monthly household income, paternal age at birth and maternal BMI, were related to the protective pattern (all P<0.05) except for the paternal BMI. After adjusting for gender, age, locations of residence (urban-rural) and BMI z-score, children with a lower parental education level and higher monthly household income were more likely to adhere to the risk pattern (ß=-0.10, 95%CI:-0.16- -0.04; ß=0.07, 95%CI: 0.02-0.12, respectively). For the protective pattern, the scores were positively associated with parental education level (ß=0.08, 95%CI: 0.02-0.14), monthly household income (ß=0.06, 95%CI: 0.02-0.11) and maternal age at birth (ß=0.02, 95%CI: 0.00-0.03). Children from the one-child families were more likely to adhere to the protective pattern (ß=-0.13, 95%CI: -0.22- -0.03). Conclusions: Differences of dietary behaviors were seen among children and adolescents from families with different characteristics. Protective patterns for children from families with lower parental education, lower monthly household income, lower maternal age at birth or multiple children etc. should be promoted. Risk patterns of children with lower parental educational or higher monthly household income also need to be corrected.

Experimental and observational studies find contrasting responses of soil nutrients to climate change.

Manipulative experiments and observations along environmental gradients, the two most common approaches to evaluate the impacts of climate change on nutrient cycling, are generally assumed to produce similar results, but this assumption has rarely been tested. We did so by conducting a meta-analysis and found that soil nutrients responded differentially to drivers of climate change depending on the approach considered. Soil carbon, nitrogen, and phosphorus concentrations generally decreased with water addition in manipulative experiments but increased with annual precipitation along environmental gradients. Different patterns were also observed between warming experiments and temperature gradients. Our findings provide evidence of inconsistent results and suggest that manipulative experiments may be better predictors of the causal impacts of short-term (months to years) climate change on soil nutrients but environmental gradients may provide better information for long-term correlations (centuries to millennia) between these nutrients and climatic features. Ecosystem models should consequently incorporate both experimental and observational data to properly assess the impacts of climate change on nutrient cycling.

Functional expression of P2X4 receptor in capillary endothelial cells of the cochlear spiral ligament and its role in regulating the capillary diameter.

The cochlear lateral wall generates the endocochlear potential (EP), which creates a driving force for the hair cell transduction current and is essential for normal hearing. Blood flow at the cochlear lateral wall is critically important for maintaining the EP. The vulnerability of the EP to hypoxia suggests that the blood flow in the cochlear lateral wall is dynamically and precisely regulated to meet the changing metabolic needs of the cochlear lateral wall. It has been reported that ATP, an important extracellular signaling molecule, plays an essential role in regulating cochlear blood flow. However, the cellular mechanism underlying ATP-induced regional blood flow changes has not been investigated. In the current study, we demonstrate that 1) the P2X4 receptor is expressed in endothelial cells (ECs) of spiral ligament (SL) capillaries. 2) ATP elicits a characteristic current through P2X4 on ECs in a dose-dependent manner (EC(50) = 0.16 mM). The ATP current has a reversal potential at ∼0 mV; is inhibited by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD), LaCl(3), pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), and extracellular acidosis; and is less sensitive to α,ß-methyleneadenosine 5'-triphosphate (α,ß-MeATP) and 2'- and 3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate (BzATP). 3) ATP elicits a transient increase of intracellular Ca(2+) in ECs. 4) In accordance with the above in vitro findings, perilymphatic ATP (1 mM) caused dilation in SL capillaries in vivo by 11.5%. N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nonselective inhibitor of nitric oxide synthase, or 5-BDBD, the specific P2X4 inhibitor, significantly blocked the dilation. These findings support our hypothesis that extracellular ATP regulates cochlear lateral blood flow through P2X4 activation in ECs.

Carotid baroreflex responsiveness during dynamic exercise in humans.

We utilized 5-s changes of neck pressure and neck suction (from 40 to -80 Torr) to alter carotid sinus transmural pressure in seven men with peak oxygen uptake (VO2peak) of 41.4 +/- 3.6 ml O2.kg-1.min-1. Peak responses of heart rate (HR) and mean arterial pressure (MAP) to each carotid sinus perturbation were used to construct open-loop baroreflex curves at rest and during exercise at 25.7 +/- 1.1 and 47.4 +/- 1.9% VO2peak. The baroreflex curves were fit to a logistic function describing the sigmoidal nature of the carotid sinus baroreceptor reflex. Maximal gain for baroreflex control of HR (-0.31 +/- 0.05 beats.min-1.mmHg-1) and MAP (-0.30 +/- 0.08 mmHg/mmHg) at rest was the same as during exercise at 25 and 50% VO2peak (-0.30 +/- 0.05, -0.39 +/- 0.13 beats.min-1.mmHg-1 for HR, P = NS; -0.23 +/- 0.04, -0.60 +/- 0.38 mmHg/mmHg for MAP, P = NS). Resetting of the baroreflex occurred during exercise at 50% VO2peak. The centering point, threshold, and saturation pressures were significantly increased for baroreflex control of HR (delta pressure = 26.3 +/- 6.8, 19.6 +/- 10.4, 33.0 +/- 5.6 mmHg, P < 0.05) and MAP (delta pressure = 27.1 +/- 7.7, 16.1 +/- 14.8, 38.2 +/- 8.5 mmHg, P < 0.05). The operating point (steady-state HR and MAP) was shifted closer to threshold of the baroreflex during exercise at 50% VO2peak, as reflected by differences in HR and MAP between the centering and operating points (delta HR = 12.5 +/- 4.7 beats/min, P = 0.10; delta MAP = 7.6 +/- 1.3 mmHg, P < 0.05). These findings suggest a resetting of the carotid baroreflex during exercise with no attenuation in maximal sensitivity. A shift in operating point toward threshold of the baroreflex enables effective buffering of elevations in systemic blood pressure via reflex alterations in HR and MAP.

[Long-term curative effect of cryotherapy for malignant ocular tumours].

66 malignant cases (2.7%) among 2401 patients of ocular tumours were treated with cryotherapy, and the tumours disappeared with satisfactory functional and cosmetic results. The cases were followed up 3-10 years (70% over 5 years), averaging 6.5 years. 6 cases (9%) recurred, 5 cases in the first and 1 case in the 9th postoperative year. The author analysed the causes of recurrence and discussed means to prevent it.

Effect of saline infusion during exercise on thermal and circulatory regulations.

To quantify the effect of an acute increase in plasma volume (PV) on forearm blood flow (FBF), heart rate (HR), and esophageal temperature (Tes) during exercise, we studied six male volunteers who exercised on a cycle ergometer at 60% of maximal aerobic power for 50 min in a warm [(W), 30 degrees C, less than 30% relative humidity (rh)] or cool environment [(C), 22 degrees C, less than 30% rh] with isotonic saline infusion [Inf(+)] or without infusion [Inf(-)]. The infusion was performed at a constant rate of 0.29 ml.kg body wt-1.min-1 for 20-50 min of exercise to mimic fluid intake during exercise. PV decreased by approximately 5 ml/kg body wt within the first 10 min of exercise in all protocols. Therefore, PV in Inf(-) was maintained at the same reduced level by 50 min of exercise in both ambient temperatures, whereas PV in Inf(+) increased toward the preexercise level and recovered approximately 4.5 ml/kg body wt by 50 min in both temperatures. The restoration of PV during exercise suppressed the HR increase by 6 beats/min at 50 min of exercise in W; however, infusion had no effect on HR in C. In W, FBF in Inf(+) continued to increase linearly as Tes rose to 38.1 degrees C by the end of exercise, whereas FBF in Inf(-) plateaued when Tes reached approximately 37.7 degrees C. The infusion in C had only a minor effect on FBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Shift in body fluid compartments after dehydration in humans.

To investigate the influence of [Na+] in sweat on the distribution of body water during dehydration, we studied 10 volunteer subjects who exercised (40% of maximal aerobic power) in the heat [36 degrees C, less than 30% relative humidity (rh)] for 90-110 min to produce a dehydration of 2.3% body wt (delta TW). After dehydration, the subjects rested for 1 h in a thermoneutral environment (28 degrees C, less than 30% rh), after which time the changes in the body fluid compartments were assessed. We measured plasma volume, plasma osmolality, and [Na+], [K+], and [Cl-] in plasma, together with sweat and urine volumes and their ionic concentrations before and after dehydration. The change in the extracellular fluid space (delta ECF) was estimated from chloride distribution and the change in the intracellular fluid space (delta ICF) was calculated by subtracting delta ECF from delta TW. The decrease in the ICF space was correlated with the increase in plasma osmolality (r = -0.74, P less than 0.02). The increase in plasma osmolality was a function of the loss of free water (delta FW), estimated from the equation delta FW = delta TW - (loss of osmotically active substance in sweat and urine)/(control plasma osmolality) (r = -0.79, P less than 0.01). Free water loss, which is analogous to "free water clearance" in renal function, showed a strongly inverse correlation with [Na+] in sweat (r = -0.97, P less than 0.001). Fluid movement out of the ICF space attenuated the decrease in the ECF space.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of osmolality and plasma volume during rehydration in humans.

To determine how the sodium content of ingested fluids affects drinking and the restoration of the body fluid compartments after dehydration, we studied six subjects during 4 h of recovery from 90-110 min of a heat [36 degrees C, less than 30% relative humidity (rh)] and exercise (40% maximal aerobic power) exposure, which caused body weight to decrease by 2.3%. During the 1st h, subjects rested seated without any fluids in a thermoneutral environment (28 degrees C, less than 30% rh) to allow the body fluid compartments to stabilize. Over the next 3 h, subjects rehydrated ad libitum using tap water and capsules containing either placebo (H2O-R) or 0.45 g NaCl (Na-R) per 100 ml water. During the 3-h rehydration period, subjects restored 68% of the lost water during H2O-R, whereas they restored 82% during Na-R (P less than 0.05). Urine volume was greater in H2O-R than in Na-R; thus only 51% of the lost water was retained during H2O-R, whereas 71% was retained during Na-R (P less than 0.05). Plasma osmolality was elevated throughout the rehydration period in Na-R, whereas it returned to the control level by 30 min in H2O-R (P less than 0.05). Changes in free water clearance followed changes in plasma osmolality. The restoration of plasma volume during Na-R was 174% of that lost. During H2O-R it was 78%, which seemed to be sufficient to diminish volume-dependent dipsogenic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of sodium retention hormones during rehydration in humans.

We investigated the relation between involuntary dehydration and the mechanisms affecting Na+ retention in the body, focusing on the renin-angiotensin-aldosterone system. Six adult males were dehydrated to 2.3% of their body weight by an exercise-heat regimen, followed by rehydration (180 min) with tap water (H2O-R) or 0.45% NaCl solution (Na-R). We measured plasma renin activity (PRA) and aldosterone levels (PA) before dehydration (control), after dehydration, and at 60, 120, and 180 min of rehydration. During the 3-h rehydration period, subjects, restored 51% of the water lost during H2O-R and 71% during Na-R (P less than 0.05). Plasma volume was reduced by an average of 4.5% after dehydration. After 180 min of rehydration, plasma volume restoration during Na-R was to 174% of that lost, and during H2O-R it was to 78% of that lost. We found significant correlations between the change in plasma volume and PRA (r = -0.70, P less than 0.001) and between PRA and PA (r = 0.71, P less than 0.001). In both recovery conditions, PRA increased significantly after dehydration (P less than 0.05) and decreased almost to the control level by 180 min of rehydration, at which time the plasma volume deficit was restored. The change in PA paralleled that in PRA. The rate of sodium excretion was correlated with PA levels in both groups (r = -0.58, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)