Xinjiang is one of the high TB burden provinces of China. A spatial analysis was conducted using geographical information system (GIS) technology to improve the understanding of geographic variation of the pulmonary TB occurrence in Xinjiang, its predictors, and to search for targeted interventions.

To explore the effects of celecoxib on pressure overload-induced cardiac hypertrophy (CH), cardiac dysfunction and explore the possible protective mechanisms. We surgically created abdominal aortic constrictions (AAC) in rats to induce CH. Rats with CH symptoms at 4 weeks after surgery were treated with celecoxib [2 mg/100 g body-weight(BW)] daily for either 2 or 4 weeks. Survival rate, blood pressure and cardiac function were evaluated after celecoxib treatment. Animals were killed, and cardiac tissue was examined for morphological changes, cardiomyocyte apoptosis, fibrosis, inflammation and oxidative stress. Four weeks after AAC, rats had significantly higher systolic, diastolic and mean blood pressure, greater heart weight and enlarged cardiomyocytes, which were associated with cardiac dysfunction. Thus, the CH model was successfully established. Two weeks later, animals had impaired cardiac function and histopathological abnormalities including enlarged cardiomyocytes and cardiac fibrosis, which were exacerbated 2 weeks later. However, these pathological changes were remarkably prevented by the treatment of celecoxib, independent of preventing hypertension. Mechanistic studies revealed that celecoxib-induced cardiac protection against CH and cardiac dysfunction was due to inhibition of apoptosis via the murine double mimute 2/P53 pathway, inhibition of inflammation via the AKT/mTOR/NF-κB pathway and inhibition of oxidative stress via increases in nuclear factor E2-related factor-2-mediated gene expression of multiple antioxidants. Celecoxib suppresses pressure overload-induced CH by reducing apoptosis, inflammation and oxidative stress.

Sleep deprivation affects the pathophysiology of immune-inflammatory skin diseases such as psoriasis. Increasing efforts are directed toward exploring potential mechanisms involving sleep deprivation and immune responses. However, studies focusing on the effects of different timing of sleep deprivation on skin inflammation are lacking. This study thus investigated the immunomodulatory effects of paradoxical sleep (PS) deprivation at different timing of psoriasiform process on skin inflammation in the psoriasis-like mouse model. Male adult C57BL/6 mice were divided into 5 groups (each n = 5): control group (CON), IMQ-S2 group [treating with 31.25 mg imiquimod (IMQ) per day for 5 days with 48 h of PS deprivation on the fourth and fifth day], S2-IMQ group (treating with 31.25 mg IMQ per day for 5 days with 48 h of PS deprivation on the first and second day), 31.25 group (treating with 31.25 mg IMQ per day for 5 days) and 62.5 group (treating with 62.5 mg IMQ per day for 5 days). Compared with IMQ-S2 group and 31.25 group, S2-IMQ group mice had significant increase of IL-17A mRNA level in skin lesions and lymph nodes, and more severe cutaneous inflammation. However, IMQ-S2 group had the highest IL-1β mRNA level in skin lesions and the highest IL-6 mRNA level in lymph nodes among the three groups. Results of flow cytometry showed that frequencies of γδT cell, IL-17A+γδT cell, dendritic cell (DC) and MHCⅡ+ DC in lymph nodes of S2-IMQ group were significantly higher than IMQ-S2 group and 31.25 group, so was the frequency of γδT cells in skin lesions. However, the frequency of DCs in skin lesions of S2-IMQ group was significantly lower than IMQ-S2 group. These data suggest that PS deprivation at the early stage rather than the late stage of psoriasiform process exacerbates the skin inflammation through modulation of the immune system, which may involve that IL-1β and IL-6 stimulated by PS deprivation in turn increasing IL-17 expression through activation and proliferation of γδT cells and DCs migration.

Autologous bone grafting and ilizarov technique are the preferred mode of treatment for bone nonunion, studies suggest that bone marrow derived mesenchymal stem cells can be effective in treatment of tibial non-union where there is length of bone defect. The current study investigates the beneficial clinical outcome of combining the ilizarov procedure with intraosseous injection of autologous mesenchymal stem cells. The open-label study enrolled 25 patients with infected tibial non-union at the Shanghai Fengxian District Central Hospital, Shanghai, China between April 2010 and July 2014. Patients were randomised to undergo the ilizarov procedure with (n = 11) or without (n = 13) intraosseous injection of bone marrow derived mesenchymal stem cells. All participants were followed prospectively until union was achieved (primary end point). The mean length of the bone defect in the Ilizarov group and Ilizarov group plus MSC group was 6.09 and 5.84 cm respectively. The mean time from the original injury to the time of the treatment for tibial non-union was 5-22 months (mean 13.5 months) for the Ilizarov group and 6-21 months (mean 13.5 months) for Ilizarov plus MSc group. All 24 patients were followed up for 12-34 months (mean 16 months). Both groups achieved the primary endpoint of stable union of the tibial fracture. No adverse events were observed in any of the group. Our study demonstrates that using autologous bone marrow derived mesenchymal stem cell as an add-on therapy to the ilizarov procedure shows significant clinical benefit in fixation of tibial non-union.

Circulating tumor cells (CTCs) serves a primary function in metastasis and recurrence of hepatocellular carcinoma (HCC). In the present study, in order to evaluate the analytical performance and clinical value of the liquid biopsy-based platform, a novel integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (iFISH®) platform was applied to analyze CTCs in patients with HCC undergoing liver transplantation (LT). In total, 30 patients with HCC undergoing LT and 10 healthy volunteers were enrolled. CTCs in peripheral blood that were obtained from each patient prior to LT and 3 months thereafter were detected using the iFISH® platform, and CellSearch® system was performed for each subject for comparison. Using iFISH® and CellSearch®, the percentage of CTCs in patients with pre-operative HCC were 70.00% and 26.67%, respectively. CTCs counted using iFISH® (iFISH-CTCs) were increased compared with CellSearch® (Cellsearch-CTCs) (P<0.01). A significant decrease in iFISH-CTCs was observed 3 months following LT (3.04±0.93/7.5 to 1.0±0.53/7.5 ml, P<0.05). Furthermore, patients with lower preoperative iFISH-CTCs level (<5/7.5 ml) had markedly increased recurrence-free survival compared with iFISH-CTCs (>5/7.5 ml, 15 vs. 5.5 months; P<0.01. iFISH® platform exhibits an increased analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs, and CTCs may be a good prognostic indicator for patients with HCC undergoing LT.

Phosphorus (P) is arguably more limiting than nitrogen for forest ecosystems being free of disturbances for lengthy time periods. The elucidation of multivariate relationships between foliar P and its primary drivers for dominant species is an urgent issue and formidable challenge for ecologists. Our goal was to evaluate the effects of primary drivers on foliar P of Quercus wutaishanica, the dominant species in broadleaved deciduous forest at the Loess Plateau, China. We sampled the leaves of 90 Q. wutaishanica individuals across broad climate and soil nutrient gradients at the Loess Plateau, China, and employed structural equation models (SEM) to evaluate multiple causal pathways and the relative importance of the drivers for foliar P per unit mass (Pmass) and per unit area (Parea). Our SEMs explained 73% and 81% of the variations in Pmass and Parea, respectively. Pmass was negatively correlated to leaf mass per area, positively correlated to leaf area, and increased with mean annual precipitation and total soil potassium. Parea was positively correlated to leaf mass per area, leaf dry weight, and increased significantly with total soil potassium. Our results demonstrated that leaf P content of Q. wutaishanica increased with total soil potassium in the Loess Plateau accordingly.

Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.

Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin.

Although behavioral and neuropsychological studies have suggested two distinct routes of phonological access, their neural substrates have not been clearly elucidated. Here, we designed an artificial language (based on Korean Hangul) that can be read either through addressed (i.e., whole word mapping) or assembled (i.e., grapheme-to-phoneme mapping) phonology. Two matched groups of native English-speaking participants were trained in one of the two conditions, one hour per day for eight days. Behavioral results showed that both groups correctly named more than 90% of the trained words after training. At the neural level, we found a clear dissociation of the neural pathways for addressed and assembled phonologies: There was greater involvement of the anterior cingulate cortex, posterior cingulate cortex, right orbital frontal cortex, angular gyrus and middle temporal gyrus for addressed phonology, but stronger activation in the left precentral gyrus/inferior frontal gyrus and supramarginal gyrus for assembled phonology. Furthermore, we found evidence supporting the strategy-shift hypothesis, which postulates that, with practice, reading strategy shifts from assembled to addressed phonology. Specifically, compared to untrained words, trained words in the assembled phonology group showed stronger activation in the addressed phonology network and less activation in the assembled phonology network. Our results provide clear brain-imaging evidence for the dual-route models of reading.

Dermal IL-17-producing γδT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ(-/-) mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.

An intriguing discovery in recent years is that resting-state functional connectivity (RSFC) is associated with cognitive performance. The current study investigated whether RSFC within the reading network was correlated with Chinese adults' reading abilities in their native language (L1, Chinese) and second language (L2, English). Results showed that RSFC within the reading network was positively correlated to reading abilities in L1 and L2, and RSFC between reading areas and the default network was negatively correlated to reading abilities in L1 and L2. Further conjunction and contrast analyses revealed that L1 and L2 shared similar RSFC correlates including connectivities between the areas for visual analysis (e.g., bilateral posterior fusiform gyrus, lateral occipital cortices, and right superior parietal lobules) and those for phonological processing (e.g., bilateral precentral gyri and postcentral gyrus, Wernicke's area). These results indicate that RSFC is a potential neural marker for reading abilities in both L1 and L2, with important theoretical implications for reading in L1 and L2.

Wear debris-induced osteogenic inhibition and bone destruction are critical in the initiation of peri-prosthetic osteolysis. However, the molecular mechanism underlying this phenomenon is poorly understood. In this study, we analyzed the involvement of the GSK-3β/β-catenin signal pathway, which is important for bone formation in this pathological condition. We established a titanium (Ti) particle-stressed murine MC3T3-E1 cell culture system and calvariae osteolysis model to test the hypothesis that Ti particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway. Our findings showed that Ti particles reduced osteogenic differentiation induced by osteogenesis-related gene expression, alkaline phosphatase activity and matrix mineralization, as well as pSer9-GSK-3β expression and β-catenin signal activity. Downregulation of GSK-3β activity attenuated Ti particle-induced osteogenic inhibition, whereas the β-catenin inhibitor reversed this protective effect. Moreover, the GSK-3β/β-catenin signal pathway mediated the upregulation of RANKL and downregulation of OPG in Ti particle-stressed MC3T3-E1 cells. In addition, our in vivo results showed that Ti particles induced bone loss via regulating GSK-3β and β-catenin signals. Based on these results, we concluded that the GSK-3β/β-catenin signal pathway mediates the adverse effects of Ti particles on osteoblast differentiation and bone destruction, and can be used as a potential therapeutic target for the treatment of peri-prosthetic osteolysis.

To investigate the association of several single nucleotide polymorphisms (SNPs) within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene and additional gene- gene and gene- type 2 diabetes mellitus (T2DM) interaction with pulmonary tuberculosis (PTB) risk in Chinese Uygur population.

Disseminated intravascular coagulation (DIC) is a common life-threatening complication in critically ill patients. The diagnostic scoring systems of DIC enable a more prompt and accurate diagnosis of DIC, such as the International Society on Thrombosis and Haemostasis (ISTH), the Japanese Association for Acute Medicine (JAAM) and the Japanese Ministry of Health and Welfare (JMHW). This study prospectively evaluated the newly proposed Chinese DIC Scoring System (CDSS), which was conducted at 18 centers in China during a one-year period. Receiver operating characteristic (ROC) curves showed that, for diagnosis of DIC and for prediction of the 28-day all-cause mortality, the CDSS had larger areas under the ROC curve (AUCs) than the ISTH and the JAAM in different groups. The CDSS also had larger AUC than the JMHW for the ISTH DIC in non-infectious diseases. All of the AUCs of the CDSS were greater than 0.8, accompanied with both high sensitivity and high specificity. Furthermore, the CDSS score was an independent predictor of mortality (odds ratio, 1.882; p < 0.001), and could reflect the illness severity (p < 0.001 for Spearman's rank correlations with the scores of severity). In conclusion, the CDSS is worthy of promotion with a better diagnostic and prognostic value for DIC.

Treatment of glioblastoma using radiotherapy and chemotherapy has various outcomes, key among them being cellular senescence. However, the molecular mechanisms of this process remain unclear. In the present study, we tested the ability of D-galactose (D-gal), a reducing sugar, to induce senescence in glioblastoma cells. Following pretreatment with D-gal, glioblastoma cell lines (C6 and U87MG) showed typical characteristics of senescence. These included the reduced cell proliferation, hypertrophic morphology, increased senescence-associated β-galactosidase activity, downregulation of Lamin B1, and upregulation of several senescence-associated genes such as p16, p53, and NF-κB. Furthermore, our results showed that D-gal was more suitable than etoposide (a DNA-damage drug) in inducing senescence of glioblastoma cells. Mechanistically, D-gal inactivated the YAP-CDK6 signaling pathway, while overexpression of YAP or CDK6 could restore D-gal-induced senescence of C6 cells. Finally, metformin, an anti-aging agent, activated the YAP-CDK6 pathway and suppressed D-gal-induced senescence of C6 cells. Taken together, these findings established a new model for analyzing senescence in glioblastoma cells, which occurred through the YAP-CDK6 pathway. This is expected to provide a basis for development of novel therapies for the treatment of glioblastoma.

MicroRNAs (miRNAs or miRs) serve crucial roles in the progression of osteoporosis. This study investigated the role and specific molecular mechanism of miR-135-5p in regulating osteoblast differentiation and calcification.

Density of tumor infiltrating lymphocytes (TIL) and expressions of certain immune-related genes have prognostic and predictive values in hepatocellular carcinoma (HCC); however, factors determining the immunophenotype of HCC patients are still unclear. In the current study, the transcript sequencing data of liver cancer were systematically analyzed to determine an immune gene marker for the prediction of clinical outcome of HCC.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with multifactorial etiology. The role of microglia in the pathogenesis of AD has been increasingly recognized in recent years; however, the detailed mechanisms shaping microglial phenotypes in AD-relevant pathological settings remain largely unresolved. Myocyte-specific enhancer factor 2C (Mef2C) is a transcription factor with versatile functions. Recent studies have attributed aging-related microglial changes to type I interferon (IFN-I)-associated Mef2C deregulation. In view of the close relationship between brain aging and AD, it is of great interest to determine microglial Mef2C changes in AD-related conditions. In this study, we have found that suppressed Mef2C nuclear translocation was an early and prominent microglial phenotype in a mouse model of brain amyloidosis (5×FAD mice), which exacerbated with age. Echoing the early Mef2C deregulation and its association with microglial activation, transcriptional data showed elicited IFN-I response in microglia from young 5×FAD mice. Amyloid beta 42 (Aβ42) in its oligomeric forms promoted Mef2C deregulation in microglia on acute organotypic brain slices with augmented microglial activation and synapse elimination via microglial phagocytosis. Importantly, these oligomeric Aβ42-mediated microglial changes were substantially attenuated by blocking IFN-I signaling. The simplest interpretation of the results is that Mef2C, concurring with activated IFN-I signaling, constitutes early microglial changes in AD-related conditions. In addition to the potential contribution of Mef2C deregulation to the development of microglial phenotypes in AD, Mef2C suppression in microglia may serve as a potential mechanistic pathway linking brain aging and AD.

The purpose of the study was to evaluate the effect of local application of vancomycin powder (VP) to prevent surgical site infections (SSIs) after posterior spine surgery. A comprehensive search of Web of Science, EMBASE, Pubmed, Ovid, and Cochrane Library databases for articles published was performed to collect comparative studies of intrawound vancomycin in posterior spine surgery before March 2021. Two reviewers independently screened eligible articles based on the inclusion and exclusion criteria, assessed the study quality, and extracted the data. Revman 5.4 software was used for data analysis. A total of 22 articles encompassing 11 555 surgical patients were finally identified for meta-analysis. According to the information provided by the included literature, the combined odds ratio showed that topical use of VP was effective for reducing the incidence of SSIs (P< 0.00001) after posterior spine surgery without affecting its efficacy in the treatment of deep infections (P< 0.00001). However, there is no statistical significance in superficial infections. In a subgroup analysis, VP at a dose of 1, 2, and 0.5-2 g reduced the incidence of spinal SSIs. The result of another subgroup analysis suggested that local application of VP could significantly reduce the risk of SSIs, whether it was administered after posterior cervical surgery or thoracolumbar surgery. Moreover, the percentage of SSIs due to gram-positive germs (P< 0.00001) and MRSA (P< 0.0001) could reduce after intraoperative VP was used, but did not significantly reduce to gram-negative germs. The local application of VP appears to protect against SSIs, gram-positive germs, and MRSA (methicillin-resistant Staphylococcus aureus) infections after the posterior spinal operation.

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus-host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.