Complications analysis of Ilizarov bone transport technique in the treatment of tibial bone defects-a retrospective study of 199 cases.

BACKGROUND: The clinical treatment of long bone defets in the extremities caused by trauma, infection, tumours, and nonunion has been a challenge for orthopaedic surgeons. Bone transport techniques have become the only way to treat such bone defects. However, inevitable difficulties and complications related to bone transport techniques have been reported in many studies. AIM: The purpose of this study was to investigate the risk factors for complications and the effectiveness of the Ilizarov bone transport technique in the treatment of tibial bone defects. METHODS: The study was conducted in 199 patients who underwent treatment with the Ilizarov bone transport technique at our institution from May 2012 to September 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, a risk factor analysis was performed for the top three major complications. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria at the last clinical follow-up. RESULTS: A total of 199 patients underwent follow-up for 12-40 months, with an average of 23.5 months, and all achieved bone healing. A total of 310 complications occurred, with an average of 1.04 minor complications and 0.48 major complications per patient. The top three complications were pin tract infection in 48 cases (61.3%), axial deviation in 86 cases (43.2%), and delayed union in 50 cases (25.13%). Multivariate analysis showed that the bone defect length (P = 0.02, OR = 5.489), the number of previous surgeries (P = 0.003, OR = 2.204), and the external fixation index (P = 0.01, OR = 1.202) were significantly correlated with pin tract infection. Bone defects of the middle 1/3 (P < 0.001, OR = 23.769), the bone defect length (P < 0.001, OR = 2.776), and the external fixation index (P < 0.001, OR = 1.154) were significantly correlated with axial deviation. The bone defect length (P = 0.003, OR = 1.242), soft tissue defects (P = 0.013, OR = 0.312) and bone defects of the distal 1/3 (P = 0.023, OR = 4.257) were significantly correlated with delayed healing. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.48% and a rate of excellent functional results of 87.94%. CONCLUSION: The Ilizarov bone transfer technique is an effective method for treating tibial bone defects, and shortening the treatment period can reduce the incidence of complications. Older patients and those with longer bone defects, a higher external fixation index, more previous operations, and defects of the middle and distal 1/3 had a higher incidence of complications.

Prevalence of sarcopenia under different diagnostic criteria and the changes in muscle mass, muscle strength, and physical function with age in Chinese old adults.

BACKGROUND: At present, there are several diagnostic criteria of sarcopenia were used in China, and the diagnostic criteria were not unified. This study aims to investigate the consistency between the latest sarcopenia diagnostic criteria Asian Working Group for Sarcopenia(AWGS 2019) and other common diagnostic criteria. The changes of muscle mass, muscle strength and physical function with age and their effects on the diagnosis of sarcopenia were also analyzed. METHODS: A total of 1009 men aged ≥60 years were enrolled from multiple communities. Skeletal muscle mass index, grip strength and 6 m gait speed were measured. The consistency of AWGS 2019 with other diagnostic criteria was analyzed and the trends of these three indicators were observed. The differences of muscle mass, muscle strength and function among different diagnostic criteria and age groups were evaluated. In addition, the change trends of these three indicators with age were observed. RESULTS: According to AWGS 2019 diagnostic criteria, the incidence of sarcopenia in male aged 60-69 years, 70-79 years and over 80 years was 1.5%, 9.6% and 33.1%, respectively. AWGS 2019 was highly consistent with other diagnostic criteria (Kappa = 0.66-0.80, P < 0.01), except the Foundation for the National Institutes of Health(FNIH) (Kappa = 0.32, P < 0.01). When AWGSA2019 diagnostic criteria are applied, the prevalence of decreased muscle strength (39.1%) and physical function (46.4%) was significantly higher than that of low muscle mass (35.9%) in the men over 80 years old. Muscle strength (P < 0.01) and function (P < 0.01) decreased at the same rate with age, both of which were more significant than muscle mass (P < 0.01). CONCLUSION: AWGS 2019 was highly consistent with other criteria. Maintaining muscle mass should be the focus of attention before age 80, while improving muscle strength and function should be focused after age 80 to prevent disability.

Clinical characteristics of re-hospitalized COVID-19 patients with recurrent positive SARS-CoV-2 RNA: a retrospective study.

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China.

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

Pirfenidone alleviates lipopolysaccharide-induced lung injury by accentuating BAP31 regulation of ER stress and mitochondrial injury.

Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.

The anti-inflammatory effect of BML-111 on COPD may be mediated by regulating NLRP3 inflammasome activation and ROS production.

The aim of this study is to investigate whether the lipoxin receptor agonist BML-111 exerts a protective effect against inflammation in a mouse model of chronic obstructive pulmonary disease (COPD) by regulating NLRP3 inflammasome activation and reactive oxygen species (ROS) production. In this study, mice were randomly divided into the following five groups: control group (Control), COPD model group (Model), BML-111 low-dose group (Low-BML), BML-111 high-dose group (High-BML) and Dexamethasone group (Dex). NLRP3 involvement and oxidative stress were evaluated. Differential cell counts in the BALF were calculated to obtain a reliable enumeration of each cell type, and the levels of TGF-ß, TNF-α, IL-1ß, and IL-10 in BALF were evaluated using ELISA. We found that the white blood cell and lymphocyte numbers in the BALF were significantly lower in the High-BML group than in the Model group. ELISA of the BALF showed that BML-111 reduced TGF-ß and IL-1ß levels to some extent. HE staining showed various degrees of reduction in inflammatory cell infiltration in the bronchopulmonary tissue and blood vessels of the Low-BML, High-BML and Dex groups. Measurement of oxidative stress showed that SOD activity was significantly upregulated and that the increase in MDA content was prevented in the High-BML and Dex groups. According to the Western blotting analysis, the levels of NLRP3, Cleaved-IL-1ß and Cleaved-caspase-1 were decreased and Nrf-2 was increased to various extents in the Low-BML, High-BML and Dex groups. Based on these findings, BML-111 may prevent NLRP3 inflammasome activation and inhibit ROS production via upregulation of Nrf-2, thereby exerting an anti-inflammatory effect on COPD model mice.

Effects of exercise training on patients with lung cancer who underwent lung resection: a meta-analysis.

BACKGROUND: The efficacy of exercise training in patients with lung cancer after lung resection has not been well established yet. Therefore, we performed a meta-analysis to investigate the efficiency of exercise training in patients with lung cancer after lung resection. METHODS: Several databases were searched for eligible randomised controlled trials (RCTs). The primary outcome was quality of life, and the secondary outcomes included 6-min walk distance (6MWD), forced expiratory volume in 1 s (FEV1) and postoperative complications (POCs). Weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated by random-effects model. RESULTS: Six RCTs involving 438 patients were enrolled in this meta-analysis. The pooled WMDs of the scores were 2.41 (95% CI = -5.20 to 10.02; P = 0.54) and -0.46 (95% CI = -20.52 to 19.61; P = 0.96) for the physical and mental components of the 36-item short-form scale, respectively. The pooled WMDs were 23.50 m (95% CI = -22.04 to 69.03; P = 0.31) for 6MWD and 0.03 L (95% CI = -0.19 to 0.26; P = 0.76) for FEV1. Finally, the pooled RRs were 0.79 (95% CI = 0.41 to 1.53; P = 0.49) for POCs. CONCLUSIONS: Insufficient evidence is available to support the efficacy of exercise training in patients with lung cancer after lung resection. Further studies must confirm our findings and investigate the long-term effects of exercise training on patients with lung cancer following lung resection.

Meta-analysis of the risks of hypertension and QTc prolongation in patients with advanced non-small cell lung cancer who were receiving vandetanib.

BACKGROUND: A meta-analysis of published data was conducted to investigate the overall risks of hypertension and QTc prolongation in patients with advanced non-small cell lung cancer (NSCLC) who were receiving vandetanib. METHODS: A computerized search through electronic databases, including PubMed and Embase (until Dec 2014), was performed to obtain eligible randomized controlled trials (RCTs) that compared hypertension and/or QTc prolongation profile of vandetanib alone or plus chemotherapy with control groups (placebo, single targeted therapy, chemotherapy, or a combination of them) in patients with advanced NSCLC. The outcome measures were the overall risks of hypertension and QTc prolongation. Relative risk (RR) and 95% confidence interval (CI) were calculated and pooled using a random effects model. RESULTS: A total of nine RCTs, which involved 4813 patients, were enrolled in the present study. A significant increase in risk was observed for all-grade hypertension (RR 5.58; 95% CI 4.16 to 7.48; P < 0.00001) and grade ≥3 hypertension (RR 4.79; 95% CI 2.31 to 9.93; P < 0.0001) in advanced NSCLC patients who were receiving vandetanib compared with the controls. Moreover, vandetanib significantly prolonged all-grade QTc interval (RR 7.90; 95% CI 4.03 to 15.50; P < 0.00001) and grade ≥3 QTc interval (RR 3.12; 95% CI 1.01 to 9.63; P = 0.05). CONCLUSIONS: Current evidence showed that significant risks in developing hypertension and QTc prolongation exist in advanced NSCLC patients who were receiving vandetanib. Thus, appropriate monitoring and management of these events are recommended.

Transfer of the IL-37b gene elicits anti-tumor responses in mice bearing 4T1 breast cancer.

AIM: IL-37b has shown anti-cancer activities in addition to its anti-inflammatory properties. In this study, we investigated the effects of IL-37b on breast carcinoma growth in mice and to determine the involvement of T cell activation in the effects. METHODS: IL-37b gene was transferred into mouse breast carcinoma cell line 4T1 (4T1-IL37b cells), the expression of secretory IL-37b by the cells was detected, and the effects of IL-37b expression on the cell proliferation in vitro was evaluated. After injection of 4T1 cells or 4T1-IL37b cells into immunocompetent BALB/c mice, immunodeficient BALB/c nude mice and NOD-SCID mice, the tumor growth and survival rate were measured. The proliferation of T cells in vitro was also detected. RESULTS: IL-37b was detected in the supernatants of 4T1-IL37b cells with a concentration of 12.02 ± 0.875 ng/mL. IL-37b expression did not affect 4T1 cell proliferation in vitro. BALB/c mice inoculated with 4T1-IL37b cells showed significant retardation of tumor growth. BALB/c mice inoculated with both 4T1 cells and mitomycin C-treated 4T1-IL37b cells also showed significant retardation of tumor growth. But the anti-cancer activity of IL-37b was abrogated in BALB/c nude mice and NOD-SCID mice inoculated with 4T1-IL37b cells. Recombinant IL-37b slightly promoted CD4(+) T cell proliferation without affecting CD8(+) T cell proliferation. CONCLUSION: IL-37b exerts anti-4T1 breast carcinoma effects in vivo by modulating the tumor microenvironment and influencing T cell activation.

Programming of the development of tumor-promoting neutrophils by mesenchymal stromal cells.

BACKGROUND/AIMS: Neutrophils obtain immunosuppressive function during tumor development, yet the mechanisms are largely unknown. This study explored whether and how mesenchymal stromal cells (MSCs), the key component of tumor microenvironment, regulate the suppressive function of neutrophils. METHODS: Immunosuppressive function of neutrophils was evaluated by T cell proliferation assay and 4T1 breast tumor model; molecular mechanisms were explored by transcriptional profiling, Real-time RT-PCR, arginase activity assay, and iNOS inhibition experiments. RESULTS: After being cocultured with MSCs primed by TNF-α (TNF-MSCs), CD11b(+)Ly6G(+) neutrophils isolated from bone marrow of normal mice or spleen of tumor-bearing mice obtained immunosuppressive function to inhibit T cell proliferation in vitro, and to enhance 4T1 tumor progression in vivo. Moreover, arginase activity and expression of iNOS, saa3, some cytokines and chemokines and their receptors, were upregulated in neutrophils after co-culture with TNF-MSCs. Inhibition of iNOS activity attenuated the suppressive effect of TNF-MSC pre-cocultured neutrophils on T cell proliferation. CONCLUSION: MSCs program neutrophils into an immunosuppressive and tumor-promoting phenotype.

Investigation of the shared gene signatures and molecular mechanisms between obstructive sleep apnea syndrome and asthma.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is highly related with asthma from the epidemiology to pathogenesis, while the underlying mechanism is still unclear. Herein, we aimed to reveal the shared gene signatures and molecular mechanisms underlying the coexistence of OSAS and asthma and verified relating pathway in mouse models. We downloaded GSE75097 of OSAS and GSE165934 of asthma from GEO database and performed differential expression analysis and functional enrichment analysis to screen differentially expressed genes (DEGs) and potential pathogenic pathway. PPI network was constructed with the STRING database. Hub genes were identified with cytoHubba and immune infiltration analysis was performed with cibersort for further verification. Potential drugs were screened with Comparative Toxicogenomics Database and miRNA-gene network was constructed. Besides, to test the pulmonary function and inflammatory cytokine, mouse models with OSAS and asthma were constructed, followed by validating the involvement of NOD1/NOD2-RIPK2-NF-κB-MCPIP-1 pathway in associated diseases. RESULTS: In total, 104 DEGs were identified, in which PLAUR, RIPK2, PELI1, ZC3H12A, and TNFAIP8 are the hub genes, while NOD-like receptor signaling pathway and apoptosis signaling pathway were the potential influential pathways. Increased γδT cells and neutrophils were detected in asthma patients through immune infiltration analysis. Significant difference was detected among genders in OSAS, and acetaminophen is a potential drug in the comorbidity by screening the drugs in the Comparative Toxicogenomics Database. Mice with OSAS and asthma presented with worse pulmonary function and higher levels of inflammatory cytokines. The relative proteins, including NOD1, NOD2, RIPK2, NF-κB, and MCPIP-1, were up-regulated in mice with the OSAS and asthma. CONCLUSIONS: This research firstly elucidates NOD1/NOD2-RIPK2-NF-κB-MCPIP-1 pathway as the shared pathway in the development of OSAS and asthma through bioinformatics and experimental methods. There is an interactive deterioration model between OSAS and asthma. This study may provide some potential biomarkers in the future research of the underlying pathogenesis and treatment of comorbidity of OSAS and asthma.

[Analysis of Delphain lymph node detection rate, metastasis rate and risk factors for metastasis in papillary thyroid adenocarcinoma patients].

Objective:To investigate the detection rate and metastasis rate of delphain lymph node （DLN）in thyroid papillary adenocarcinoma（PTC） and to analyze the risk factors for DLN metastasis. Methods:The clinicopathological data of 200 PTC patients admitted to the from January 2018 to June 2020 were retrospectively analyzed, and the detection of DLN was clearly recorded in the pathological reports of all patients. The number of DLN detected, the number of metastasis, the detection rate and the metastasis rate were counted. The clinicopathological factors that might affect DLN metastasis were analyzed by univariate analysis and multivariate Logistic regression analysis, including gender, age, tumor size and tumor location. Results:DLN was detected in 121 of 200 PTC patients, with a detection rate of 60.50% （121/200）. DLN metastasis was found in 46 of the 121 patients with a metastasis rate of 38.02% （46/121）.Univariate analysis showed that tumor diameter, multiple foci, capsular invasion, extradandular invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were the risk factors for DLN metastasis of PTC （P<0.05）. Gender, age, tumor location, bilateral tumors, Hashimoto's thyroiditis and BRAFV600E mutation were not significantly correlated with DLN metastasis of PTC（P>0.05）. The 7 variables with statistically significant differences in univariate analysis were incorporated into Logistic regression model for multivariate analysis, and the results showed that, Tumor diameter ≥1.0 cm, capsule invasion, lymphatic vascular invasion, lymph node metastasis in central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC （OR= 3.386-9.186, P<0.05）. The sensitivity and specificity of DLN metastasis in predicting central lymph node （excluding DLN） metastasis in PTC patients were 36.79% and 92.55%, respectively, while the sensitivity and specificity of DLN metastasis in predicting lateral cervical lymph node metastasis were 41.03% and 81.37%, respectively.The incidence of central lymph node metastasis （excluding DLN） in DLN-positive patients were was 4.94 times higher than that in DLN-negative patients, and the incidence of lateral neck lymph node metastasis in DLN-positive patients were 2.20 times higher than that in DLN-negative patients. Conclusion:The detection rate and metastasis rate of DLN in PTC patients were higher, DLN metastasis predicts more extensive lymph node metastasis, and DLN metastasis was related to multiple factors,among which tumor diameter ≥ 1.0 cm, capsule invasion, lymphatic vascular infiltration, lymph node metastasis in the central region （excluding DLN）, and lateral cervical lymph node metastasis were independent risk factors for DLN metastasis of PTC. Therefore, PTC patients with the above characteristics should actively explore DLN and formulate appropriate surgical strategies.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

BACKGROUND: Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. METHODS: Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. RESULT: Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). CONCLUSION: IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Hypoxia-inducible PRMT2 addiction in glioblastomas.

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.

Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity.

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17ß-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.