Aleukemic Chronic Myeloid Leukemia Without Neutrophilia and Thrombocytosis: A Report From the BCR::ABL1 Pathology Group.

Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, 56.7% had basophilia, and 13.3% showed eosinophilia. The median number of metaphases positive for t(9;22)(q34;q11.2) was 15, with a median of 38.5% of interphase nuclei positive for BCR::ABL1 by fluorescence in situ hybridization. The median BCR::ABL1 level was 26.14%. Remarkably, 14 (45.2%) patients were initially misdiagnosed or not diagnosed before karyotype or fluorescence in situ hybridization information for BCR::ABL1 became available. Twenty-five patients received tyrosine kinase inhibitors (TKIs). One patient developed blast crisis while on TKI treatment 8 months after initial diagnosis. With a median follow-up time of 46.1 months, 20 of 22 patients who received TKI therapy and had detailed follow-up information achieved complete cytogenetic remission or deeper, 15 achieved major molecular remission or deeper, and 10 achieved molecularly undetectable leukemia. In conclusion, given the frequent occurrence of prior or concurrent malignancies, aleukemic presentation, and low level of t(9;22)(q34;q11.2)/BCR::ABL1, misdiagnosis or delayed diagnosis is common among these patients. While these patients generally respond well to TKIs, rare patients may develop blastic transformation. It is therefore important for pathologists and hematologists to be aware of this highly unusual presentation of CML to ensure timely diagnosis and appropriate management.

Arsenic exposure is associated with alterations to multiple red blood cell parameters among adults in rural Bangladesh.

Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female) in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh. Herein, we used linear regression models to estimate associations between red blood cell (RBC) parameters (i.e., RBC counts, hematocrit (HCT), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) and measurements of arsenic exposure (urinary arsenic and urinary arsenic metabolites). Arsenic exposures showed trending associations with decreased RBC counts in both men and women, a positive association with MCV in males, and an inverse association with MCHC among males, but not among non-smoking females. Among men, those who smoked had stronger associations between arsenic exposures and MCHC than non-smoking males. Collectively, our results show that arsenic exposures affect multiple RBC parameters and highlight potentially important sex differences in arsenic-induced hematotoxicity.

Acetylcytidine modification of Amotl1 by N-acetyltransferase 10 contributes to cardiac fibrotic expansion in mice after myocardial infarction.

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.

Numerical analysis of hybrid mode-locking stability in a Ho-doped fiber laser.

We numerically study a hybrid mode-locked holmium-doped fiber laser based on the coupled nonlinear Schrödinger equations, by introducing nonlinear polarization rotation and saturable absorber in a same cavity. Maps of mode-locking states related to the intracavity wave-plates are created to evaluate the stability of mode-locking. Nonlinear polarization rotation imposes negative effect of linear absorption and even reverse saturable absorption to the pulses in the hybrid cavity. Saturable absorber compensates the negative effect from nonlinear polarization rotation, then consequently contributes to the stability of single-pulse mode-locking states. The extension of pulse time duration indicates the dynamic synergy between nonlinear polarization rotation and saturable absorber rather than the static combination mechanism of them.

Criticality in transient behavior of coupled oscillator system toward chimera and synchronization.

Chimera states in spatiotemporal dynamical systems have been investigated in physical, chemical, and biological systems, while how the system is steering toward different final destinies upon spatially localized perturbation is still unknown. Through a systematic numerical analysis of the evolution of the spatiotemporal patterns of multi-chimera states, we uncover a critical behavior of the system in transient time toward either chimera or synchronization as the final stable state. We measure the critical values and the transient time of chimeras with different numbers of clusters. Then, based on an adequate verification, we fit and analyze the distribution of the transient time, which obeys power-law variation process with the increase in perturbation strengths. Moreover, the comparison between different clusters exhibits an interesting phenomenon, thus we find that the critical value of odd and even clusters will alternatively converge into a certain value from two sides, respectively, implying that this critical behavior can be modeled and enabling the articulation of a phenomenological model.

Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics.

Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.

Effects of Nivolumab and Ipilimumab on the suppression of cisplatin resistant small cell lung cancer cells.

BACKGROUND: Small cell lung cancer (SCLC) accounts for nearly 10-15% of all lung cancer cases. Although many chemotherapy drugs, such as cisplatin and etoposide, were approved as primary therapy for SCLC patients, the prognosis is poor. In this study, we aimed to explore novel therapeutic strategy against SCLC. METHODS: Two SCLC cell lines, LTEP-P and LTEP-P/DDP1.0, were treated with cisplatin, in the absence or presence of Nivolumab + Ipilimumab combination, and the cell viability was measured. Tumor size and mouse survival rate were examined upon different drug treatments. Protein levels of PD-1 and CTLA4 were detected in normal and SCLC cells by Western blot. Cellular cytotoxicity induced by T lymphocytes was measured by thymidine incorporation assay. Tumor infiltrated T cell populations from LTEP-P and LTEP/DDP1.0 tumor-bearing mice were analyzed by flow cytometry. RESULTS: LTEP-P cells, but not LTEP/DDP1.0 cells, exhibited decreased cell viability upon cisplatin, Nivolumab and Ipilimumab combinational treatment. T lymphocytes significantly inhibited the growth of LTEP-P cells in the presence of nivolumab and ipilimumab. The combinational therapy improved survival rate and inhibited tumor growth in LTEP-P tumor-bearing mice, but showed no effect on LTEP/DDP1.0 tumor-bearing mice. Nivolumab and Ipilimumab synergized with cisplatin in increasing CD8 + and CD4 + T cell population, while decreasing Treg population in LTEP-P tumor-bearing mice. CONCLUSIONS: The combinational therapy by cisplatin, Nivolumab and Ipilimumab could be an effective strategy against LTEP-P cells, accompanied with increased cytotoxic T cell populations, but has no significant effect against DDP-resistant lung adenocarcinoma cells.

Nucleophilic functionalizations of indole derivatives using the aromatic Pummerer reaction.

Because of the electron-rich property of indoles, direct functionalization strategies towards indoles generally involve electrophilic substitutions. In this paper, an efficient protocol for nucleophilic hydroxylation, halogenation and esterification of indoles via the aromatic Pummerer process was developed. With the advantages of readily accessible starting materials, simple operation and mild conditions, this protocol should be of interest to synthetic scientists.

Circular RNA hsa_circ_0068252 Functions in Cisplatin Resistance and Immune Response via miR-1304-5p/PD-L1 Axis in Non-Small Cell Lung Cancer.

BACKGROUND: Research suggests that circRNAs play important roles in non-small cell lung cancer (NSCLC). The function of hsa_circ_0068252 in NSCLC, especially in cisplatin (DDP) resistance and the mechanisms, was explored in this study. METHODS: NSCLC patient samples and two NSCLC cell lines along with corresponding DDP-resistant cell lines were used. Expression levels of circ_0068252 were detected. SiRNA for circ_0068252 and inhibitor for miRNA were used in all functional analyses. A co-culture system of NSCLC cells with CD8+ T cells was used. The cellular location of circ_0068252 was detected and its target miRNA was predicted and verified. Finally, the mechanism responsible for circ_0068252 function on PD-L1 was analyzed using luciferase reporter assay in the two DDP-resistant cell lines, as well as in the co-culture system. The cytotoxicity of T cells was detected by lactate dehydrogenase assay. RESULTS: Our findings revealed that a high level of circ_0068252 was correlated with poor prognosis of NSCLC and DDP resistance. Knockdown of circ_0068252 could promote the sensitivity of DDP-resistant NSCLC cells to DDP. Moreover, knockdown of circ_0068252 could regulate the immune microenvironment which was mediated via CD8+ T cells. Finally, circ_0068252 could up-regulate PD-L1 expression by adsorbing miR-1304-5p. CONCLUSION: The circ_0068252/miR-1304-5p/PD-L1 signal axis participates in the regulation of DDP resistance and immune escape of NSCLC cells. Our results suggest that circ_0068252 may be a potential diagnostic marker and therapeutic target for DDP-resistant NSCLC.

Association between diagnostic delay and prognosis of pulmonary tuberculosis in Shandong, China: a retrospective study.

BACKGROUND: Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. METHODS: Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. RESULTS: We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18-63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): - 4.0%, P = 0.047, 2009-2013; APC: - 6.6%, P = 0.001, 2013-2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189-1.257, 46-65 years; aOR: 1.306, 95% CI 1.267-1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447-1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699-1.821) were prone to developing long DD (> 30 days, P < 0.05). An unfavorable outcome was negatively associated with a short DD (OR: 0.876, 95% CI 0.843-0.910, P < 0.001). Sputum smear positive rate and unfavorable outcomes were positively correlated with DD duration (Spearman correlation coefficients (rs) = 1, P < 0.001). CONCLUSIONS: The DD situation remains serious; more efficient and comprehensive strategies are urgently required to minimize DD, especially for high-risk patients.

Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK.

A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1, and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1, and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.

Multifunctional Triboelectric Nanogenerator-enabled Structural Elements for Next Generation Civil Infrastructure Monitoring Systems.

There is a critical shortage in research needed to explore a new class of multifunctional structural components that respond to their environment, empower themselves and self-monitor their condition. Here, we propose the novel concept of triboelectric nanogenerator-enabled structural elements (TENG-SEs) to build the foundation for the next generation civil infrastructure systems with intrinsic sensing and energy harvesting functionalities. In order to validate the proposed concept, we develop proof-of-concept multifunctional composite rebars with built-in triboelectric nanogenerator mechanisms. The developed prototypes function as structural reinforcements, nanogenerators and distributed sensing mediums under external mechanical vibrations. Experiential and theoretical studies are performed to verify the electrical and mechanical performance of the developed self-powering and self-sensing composite structural components. We demonstrate the capability of the embedded structural elements to detect damage patterns in concrete beams at multiscale. Finally, we discuss how this new class of TENG-SEs could revolutionize the large-scale distributed monitoring practices in civil infrastructure and construction fields.

Population aging and trends of pulmonary tuberculosis incidence in the elderly.

BACKGROUND: To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly. METHODS: We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model. RESULTS: Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656-1.722), rural population cases (OR 3.411, 95% CI 3.320-3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193-1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3, P < 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005-2010 APC = -7.2%, P < 0.05; 2010-2014 APC = -22.6%, P < 0.05; 2014-2017 APC = -9.0%, P = 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48-38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4, P<0.05). CONCLUSIONS: Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets.

Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. METHODS: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. RESULTS: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance. CONCLUSIONS: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

[Design and Feasibility Study of Tracheal Intubation Device Based on Magnetic Navigation Technology].

OBJECTIVE: In the context of coronavirus disease 2019 (COVID-19) pandemic, the subject was designed to develop a new tracheal intubation device based on magnetic navigation technology to improve the success rate of tracheal intubation and reduce the risk of occupational exposure of medical staff. METHODS: The new tracheal intubation device was designed with the uniqueness of the magnetic field environment and magnetic steering of magnetic navigation technology. And preliminary magnetic navigation tracheal intubation experiments were performed on the tracheal intubation simulator. RESULTS: Magnetic navigation tracheal intubation can successfully implement tracheal intubation, and the time required is lower than that of traditional laryngoscopy. CONCLUSIONS: The tracheal intubation based on magnetic navigation technology is feasible, with high efficiency and easy operation. That is expected to be widely used for tracheal intubation during treatment of patients outside the hospital in the future. At the same time, magnetic navigation endotracheal intubation technology will be the key technology for the development of endotracheal intubation robots.

Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.

Autophagy has been demonstrated to be vital for kidney homeostasis and is centrally implicated in the pathogenesis of cisplatin-induced acute kidney injury (AKI). Lithium is a potent autophagy inducer in a number of cell types. However, it remains uncertain whether its autophagic activity is associated with a beneficial effect on renal tubular cells in AKI. This study aimed to examine the effect of lithium on renal autophagy in cisplatin-induced AKI. Mice or renal proximal tubular epithelial cells in culture were exposed to cisplatin-induced acute injury in the presence or absence of lithium treatment. AKI or tubular cell injury was evaluated, and cell signaling associated with autophagy was examined. Lithium pretreatment prominently ameliorated acute renal tubular damage in mice exposed to cisplatin insult, associated with enhanced autophagy in renal tubules, as assessed by measuring microtubule-associated protein 1A/1B-light chain 3 (LC3)BII/I expression and autophagosome formation. Consistently, in cisplatin-injured renal tubular cells in vitro, lithium enhanced autophagic activities, improved cell viability, and attenuated cell death. Mechanistically, lithium triggered AMPK-α phosphorylation and activation, which in turn positively correlated with the induced expression of autophagy-related molecules, like mammalian target of rapamycin and LC3BII/I. AMPK-α activation is likely required for lithium-induced tubular cell autophagy and protection in cisplatin-induced AKI because blockade of AMPK-α phosphorylation by compound C markedly abrogated lithium-induced autophagosome formation and mitigated the protective effect of lithium on AKI. Our findings suggest that lithium represents a promising therapeutic strategy for protecting renal tubular cells against cisplatin-induced AKI by enhancing autophagy via AMPK-α activation.-Bao, H., Zhang, Q., Liu, X., Song, Y., Li, X., Wang, Z., Li, C., Peng, A., Gong, R. Lithium targeting of AMPK protects against cisplatin-induced acute kidney injury by enhancing autophagy in renal proximal tubular epithelial cells.

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BACKGROUND: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. METHODS: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. RESULTS: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. CONCLUSION: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

BACKGROUND: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018. METHODS: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out. RESULTS: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model. CONCLUSION: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

A Guide to Brighter Phosphors-Linking Luminescence Properties to Doping Homogeneity Probed by NMR.

Crystalline powders of Ln3+ doped LaPO4 (Ln=Nd, Gd, Dy, Ho, Er, Tm, Yb) have been synthesized to serve in a case study for linking doping homogeneity as determined by NMR to luminescent properties. Samples obtained via different synthesis methods act as examples of homo- and inhomogeneous doping. The sample quality was verified by X-ray diffraction. The homogeneously doped samples show improved luminescent properties in terms of brightness and lifetime which is consistent with the interpretation that, NMR visibility curves probe the distribution of paramagnetic dopants on a similar length scale as necessary for an efficient energy transfer in crystalline phosphors i. e. between sensitizers and activators, and to killer sites. Thus "NMR homogeneity" as observed by visibility curves may serve as a tool to optimize luminescent materials.