A spatiotemporal atlas of mouse liver homeostasis and regeneration.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/ß-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.

24-hour urinary potassium excretion is negatively associated with self-reported sleep quality in the general population, independently of sleep-disordered breathing.

STUDY OBJECTIVES: To investigate the association of 24-hour urinary potassium excretion with self-reported sleep quality in the general population. METHODS: In this cross-sectional study, a population of patients aged 18 years or older was randomly selected from Xinjiang, China in 2019, 24-hour urine samples collected, and Pittsburgh Sleep Quality Index (PSQI) questionnaires assessed. Participants were divided into 2 groups (upper and lower median of 24-hour urinary potassium excretion). Poor sleep quality was defined as PSQI global score ≥ 6. Associations between 24-hour urinary potassium excretion and [24.8 mmol/L] sleep quality were assessed by multiple logistic regression analysis in total participants and those stratified by sex. RESULTS: In total, 24-hour urine samples were collected from 1,147 participants, of whom data for those with complete urine samples and PSQI data were analyzed (n = 727; mean age = 48.7 years; percentage of women = 62%). Compared with the upper median group for 24-hour urinary potassium excretion, the lower median group showed a significantly higher PSQI global score (6 vs 5, P = .011), and prevalence of poor sleep quality (51.7% vs 42.2%, P = .011). In a fully-adjusted model of multivariate logistic regression, the lower median group showed 1.50-fold increased odds for presence of poor sleep quality (95% confidence interval: 1.01-2.24, P = .045). Sex-specific analyses translated these results to women, but not to men. CONCLUSIONS: These results suggest that low potassium intake, indicated by lower potassium excretion, is associated with poor sleep quality in the general population, especially among women. Therefore, additional research is necessary to clarify the effect of increasing potassium intake to improve sleep quality. CITATION: Li M, Heizhati M, Wang L, et al. 24-hour urinary potassium excretion is negatively associated with self-reported sleep quality in the general population, independently of sleep-disordered breathing. J Clin Sleep Med. 2022;18(11):2589-2596.

WITHDRAWN: Circ_0136474 contributes to the IL-1ß-induced chondrocyte injury by binding to miR-665 to induce the FGFR1 upregulation.

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Subjective Poor Sleep Quality is Associated with Higher Blood Pressure and Prevalent Hypertension in General Population Independent of Sleep Disordered Breathing.

OBJECTIVE: To explore the relationship of subjective sleep quality with blood pressure (BP) and hypertension by considering the influence of sleep disordered breathing (SDB) and age in the general population. METHODS: We evaluated sleep quality using the Pittsburgh sleep quality index (PSQI) and SDB using NoSAS score and measured BP in randomly selected adults in China in 2019. Sleep quality is categorized into four groups as very good, fairly good, fairly bad and very bad. SDB is defined as NoSAS score ≥8. Hypertension is defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg, and/or use of antihypertensive medicine within previous 2 weeks. Multi-variable linear and logistic regression analyses were used to assess the association of global PSQI score and sleep quality with BP and prevalent hypertension. RESULTS: In the 33,341 participants (53.4% women, median age: 48 years), prevalence of hypertension significantly increased from very good to very bad sleepers in total (34.3 vs 42.6 vs 50.3 vs 58.5%), SDB (61.2 vs 68.3 vs 73.3 vs 75.5%) and non-SDB participants (26.8 vs 33.1 vs 40.1 vs 50.9%). In multiple linear regression, PSQI global score showed significant positive association with BP levels in total, SDB and non-SDB participants, consistent in sensitivity analysis by excluding participants who were taking antihypertensives, and in participants aged <60 years in age-stratified analysis. In multivariable logistic regression, odds ratio for presence of hypertension significantly increased from very good to very bad sleepers in total (1 vs 1.08 vs 1.22 vs 1.48), SDB (1 vs 1.17 vs 1.35 vs 1.28) and non-SDB participants (1 vs 1.05 vs 1.14 vs 1.53), consistent in participants aged <60 years. CONCLUSION: Poor subjective sleep quality is significantly associated with higher BP and prevalent hypertension, independent of SDB in the young- and middle-aged general population, indicating potential of improving sleep quality to lower BP and optimize hypertension management at population level.

Association of Hypertension with Mild Cognitive Impairment in Population from Less-Developed Areas of Multiethnic Northwest China.

BACKGROUND: Relationship between hypertension and mild cognitive impairment (MCI) remains undetermined in population from less-developed regions. We aimed to explore whether hypertension is associated with MCI in this specific population. METHODS: In this cross-sectional study, we enrolled subjects aged ≥18 years using multistage random sampling from Emin, China, in 2019. Participants underwent questionnaires and data collection including mini-mental state examination (MMSE) and blood pressure measurement. RESULTS: Finally, 31,329 subjects were included, with 11,270 hypertensives. Compared with normotensive subjects, hypertensives were characterized by significantly older age (55.19 ± 12.25 vs. 43.26 ± 12.71), more men (52.5% vs. 42.9%), low education attainment (≤primary education: 42.4% vs. 26.3%), more abdominal obesity (39.7% vs. 19.1%), poor sleep quality (39.1% vs. 28.7%), and chronic kidney disease (6.6% vs. 3.4%, p for all <0.001). Prevalence of MCI in hypertensives was significantly higher than that of normotensive subjects (24.3% vs. 15.6%, p < 0.001). Multivariate logistic regression analysis showed in a fully adjusted model that the odds for MCI were significantly increased in hypertensives than in normotensive population (OR = 1.19, 95% CI: 1.09, 1.30, p < 0.001) and independent of all the parameters studied including age, education level, and stroke. In the age-stratified regression model, presence of hypertension significantly increased the odds of MCI by 1.17-fold (95% CI: 1.03, 1.33, p = 0.020) and by 1.22-fold (95% CI: 1.04, 1.44, p = 0.016) in middle-aged and elderly population. Sensitivity analysis of excluding those with stroke history showed that hypertension was still a risk factor for MCI in total, middle-aged, and elderly population. CONCLUSION: Hypertension is in independent negative association with MCI in middle-aged and elderly population from underdeveloped regions.

Association between 24-h urinary sodium to potassium ratio and mild cognitive impairment in community-based general population.

OBJECTIVE: To explore the relationship between parameters of Na and K excretion using 24-h urine sample and mild cognitive impairment (MCI) in general population. DESIGN: This is a cross-sectional study. SETTING: Community-based general population in Emin China. PARTICIPANTS: Totally, 1147 subjects aged ≥18 years were selected to complete the study, with a multistage proportional random sampling method. Cognitive status was assessed with Mini Mental State Examination (MMSE) questionnaire and timed 24-h urine specimens were collected. Finally, 561 participants aged ≥35 years with complete urine sample and MMSE data were included for the current analysis and divided into groups by tertiles of 24-h urinary sodium to potassium ratio (24-h UNa/K) as lowest (T1), middle (T2) and highest (T3) groups. RESULTS: The MMSE score was significantly lower in T3, compared with the T1 group (26·0 v. 25·0, P = 0·002), and the prevalent MCI was significantly higher in T3 than in T1 group (11·7 % v. 25·8 %, P < 0·001). In multiple linear regression, 24-UNa/K (ß: -0·184, 95 % CI -0·319, -0·050, P = 0·007) was negatively associated with MMSE score. In multivariable logistic regression, compared with T1 group, 24-h UNa/K in the T2 and T3 groups showed 2·01 (95 % CI 1·03, 3·93, P = 0·041) and 3·38 (95 % CI 1·77, 6·44, P < 0·001) fold odds for presence of MCI, even after adjustment for confounders. More augmented results were demonstrated in sensitivity analysis by excluding individuals taking anti-hypertensive agents. CONCLUSIONS: Higher 24-h UNa/K is in an independent association with prevalent MCI.

Prevalence and predictive nomogram of depression among hypertensive patients in primary care: A cross-sectional study in less developed Northwest China.

ABSTRACT: Hypertensive patients commonly co-exist persistent depressive symptoms. However, these issues are not always identified, especially in primary health care, which may worsen the prognosis of hypertension. Therefore, the aim of this study was to determine the prevalence and risk factor of depression, and to develop risk nomogram of depression in hypertensive patients from primary health care Northwest China.We used a stratified multistage random sampling method to obtain 1856 hypertensives subjects aged ≥18 years in Xinjiang between April and October 2019. The subjects were randomly divided into a training set (n = 1299) and a validation set (n = 557). Depression was evaluated by Hospital Anxiety and Depression Scale (HADS), with a cut-off score ≥8. Using the least absolute shrinkage and selection operator (LASSO) regression model, we identified optimized risk factors of depression in the training set, followed by the establishment of prediction nomogram. The discriminative ability, calibration, and clinical usefulness of nomogram were assessed. The results were verified by internal validation in validation set.13.7% hypertensive subjects displayed depression. Seven independent risk factors of depression were identified and entered into the nomogram including age, region, ethnicity, marital status, physical activity, sleep quality, and control of hypertension. The nomogram displayed robust discrimination with an AUC of 0.760 [95% confidence interval (CI): 0.724-0.797)] and 0.761 (95%CI: 0.702-0.819), and good calibration in training set and validation set, respectively. The decision curve analysis and clinical impact curve demonstrated clinical usefulness of predictive nomogram.There is a considerable prevalence of depression in patients with hypertension from primary care of Xinjiang, Northwest China. Our nomogram may help primary care providers assess the risk of depression in patients with hypertension.

Distribution characteristics of circulating homocysteine and folate and related factors in agriculture, stock-raising and urban populations: a cross-sectional survey.

OBJECTIVE: To investigate homocysteine (Hcy) and folate levels, prevalence of hyperhomocysteinaemia (HHcy) and folate deficiency, which are affected by lifestyles in urban, agricultural and stock-raising populations. DESIGN: This is a cross-sectional study. SETTING: Urban, agricultural and stock-raising regions in Emin, China. PARTICIPANTS: Totally 1926 subjects - 885 (45·9 %) from urban, 861 (44·7 %) from agricultural and 180 (9·4 %) from stock-raising regions - were obtained using multistage stratified random sampling. Inclusion criteria encompassed inhabitants aged ≥15 years who resided at the current address for ≥6 months and agreed to participate in the study. Surveys on health behaviour questionnaires and physical examinations were conducted and blood samples collected. RESULTS: The folate level of subjects from the stock-raising region was the lowest, followed by those from the agricultural region, and the highest in those from the urban region (3·48 v. 6·50 v. 7·12 ng/ml, P < 0·001), whereas mean Hcy showed no significant difference across regions. The OR for HHcy in stock-raising regions was 1·90 (95 % CI 1·11, 3·27) compared with the urban region after adjusting for all possible covariates. The OR for folate deficiency in stock-raising and agriculture regions was 11·51 (95 % CI 7·09, 18·67) and 1·91 (95 % CI 1·30, 2·82), respectively, compared with the urban region after adjusting for all possible covariates. CONCLUSIONS: HHcy and folate deficiency are highly prevalent in stock-raisers, which is of important reference for HHcy control in Xinjiang, with a possibility of extension to others with approximate lifestyles.

Prevalence of mild cognitive impairment is higher in hypertensive population: a cross-sectional study in less developed northwest China.

Uncertainty remains about the association of hypertension with mild cognitive impairment (MCI) in less-developed areas.This is a cross-sectional survey conducted in Xinjiang, a less-developed region in China between April and October 2019. We used multi-stage stratified sampling method to obtain study population aged ≥45 years, and we analyzed complete data for 3282 subjects. The Mini-Mental State Examination (MMSE) was used to assess cognitive function. MCI is defined as an MMSE score < 17 for illiterate subjects, <20 for subjects with 1 to 6 years of education, and <24 for subjects with ≥7 years of education.The prevalence of MCI was significantly higher in hypertensive subjects than in non-hypertensive subjects (22.1% vs 16.1%, P < .001) and higher in hypertensives with uncontrolled blood pressure (BP) than in those with controlled BP (27.5% vs 20.7%, P = .01). Hypertensive subjects had significantly lower each item score and total score of MMSE, compared to non-hypertensive subjects. Significant negative correlations were observed between systolic and diastolic BP with MMSE scores (P for all <.001). Multivariate logistic regression analysis showed that hypertension was the significant risk factor for the presence of MCI (OR = 1.62, 95%CI: 1.34, 2.35, P < .001), independent of such factors as gender, age, education attainment, and dyslipidemia.The prevalence of MCI is higher in hypertensive population, and hypertension is an independent risk factor for MCI in less-developed region, suggesting that hypertensives should be screened for MCI to provide improved diagnoses and optimal therapeutics for cognitive decline prevention, specially in settings with approximate conditions.

Phytic acid attenuates upregulation of GSK-3ß and disturbance of synaptic vesicle recycling in MPTP-induced Parkinson's disease models.

Heightened activity of glycogen synthase kinase-3ß (GSK-3ß) is linked to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Phytic acid (PA), a naturally occurring compound with potent antioxidant property, has been shown to confer neuroprotection on dopaminergic neurons in PD. However, the underlying mechanism remains unclear. In the present study, MPTP and MPP+ treatments were used to model PD in mice and SH-SY5Y cells, respectively. We observed reduced tissue dopamine, disrupted synaptic vesicle recycling, and defective neurotransmitter exocytosis. Furthermore, expression of GSK-3ß was upregulated while that of ß-catenin was downregulated, concentration of cytosolic calcium was increased, and expressions of two dopamine carriers, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were decreased. PA treatment attenuated the MPTP-induced upregulation of GSK-3ß, increase in cytosolic calcium concentration, decreases in the levels of DAT, VMAT2, tissue dopamine, and synaptic vesicle recycling. Importantly, disturbances in synaptic vesicle recycling are thought to be early events in PD pathology. These findings suggest that PA is a promising therapeutic agent to treat early events in PD.

Surgical treatment of combined posterior root tears of the lateral meniscus and ACL tears.

BACKGROUND: The treatment of anterior cruciate ligament (ACL) rupture complicated with posterior lateral meniscus root (PLMR) tears remains controversial. The goal of this study was to evaluate clinical outcomes of PLMR tear refixation versus left untreated at the time of reconstruction. MATERIAL/METHODS: From August 2001 to January 2012, 31 patients who undergone repair of PLMR tears were evaluated and compared with a matched control group with untreated PLMR tears. Clinical evaluation consisted of the Lysholm scale, subjective International Knee Documentation Committee (IKDC) questionnaires, and radiographic evaluation with MRI. RESULTS: Regarding to the Lysholm score and the subjective questionnaire score, there were no statistical difference between the 2 groups. However, patients after operative treatment reach higher functional scores and lower rates of osteoarthritis (normal: group A, 80%, and group B, 48%, respectively) with statistical significance (P<0.05) compared to the matched control group. CONCLUSIONS: Surgical and conservative treatment of the PLMR can both effectively improve knee function. However, a tendency towards higher functional scores and lower rates of osteoarthritis for patients with operative treatment was observed.

Genetic susceptibility of early aseptic loosening after total hip arthroplasty: the influence of TIMP-1 gene polymorphism on Chinese Han population.

OBJECTIVE: Genetic factor plays an important role in early failure of total hip arthroplasty (aseptic loosening) etiology, and TIMP-1 gene may be involved. The present study was conducted to reveal possible association between TIMP-1 polymorphisms with the risk of early failure of total hip arthroplasty (THA) (aseptic loosening). METHODS: The TIMP-1 single nucleotide polymorphisms (SNPs) rs4898, rs6609533, and rs2070584 were genotyped in 59 subjects who were diagnosed as aseptic loosening after total hip arthroplasty and in 100 controls. RESULTS: The TIMP-1 SNP rs4898 T allele in the case group was found to be 1.32 fold (P = 0.0013, 95% CI = 1.16 to 1.58) than the control group. Similarly, the G allele of rs6609533 was found to be associated with increased risk of aseptic loosening (OR = 1.78, 95% CI = 1.52 to 2.17, P < 0.0001). For SNP rs2070584, no statistical association was found (A vs. G, OR = 1.14, 95% CI = 0.97 to 1.40, P = 0.2028). CONCLUSION: The results showed that the TIMP-1 SNPs rs4898 and rs6609533 were associated with the increased risk of early aseptic loosening susceptibility.