YTHDF2/m6 A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs.

N6 -methyladenosine (m6 A) in messenger RNA (mRNA) regulates immune cells in homeostasis and in response to infection and inflammation. The function of the m6 A reader YTHDF2 in the tumor microenvironment (TME) in these contexts has not been explored. We discovered that the loss of YTHDF2 in regulatory T (Treg) cells reduces tumor growth in mice. Deletion of Ythdf2 in Tregs does not affect peripheral immune homeostasis but leads to increased apoptosis and impaired suppressive function of Treg cells in the TME. Elevated tumor necrosis factor (TNF) signaling in the TME promotes YTHDF2 expression, which in turn regulates NF-κB signaling by accelerating the degradation of m6 A-modified transcripts that encode NF-κB-negative regulators. This TME-specific regulation of Treg by YTHDF2 points to YTHDF2 as a potential target for anti-cancer immunotherapy, where intratumoral Treg cells can be targeted to enhance anti-tumor immune response while avoiding Treg cells in the periphery to minimize undesired inflammations.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.

Antimony trioxide (AT) is used as a flame retardant in fabrics and plastics. Occupational exposure in miners and smelters is mainly through inhalation and dermal contact. Chronic inhalation exposure to AT particulates in B6C3F1/N mice and Wistar Han rats resulted in increased incidences and tumor multiplicities of alveolar/bronchiolar carcinomas (ABCs). In this study, we demonstrated Kras (43%) and Egfr (46%) hotspot mutations in mouse lung tumors (n = 80) and only Egfr (50%) mutations in rat lung tumors (n = 26). Interestingly, there were no differences in the incidences of these mutations in ABCs from rats and mice at exposure concentrations that did and did not exceed the pulmonary overload threshold. There was increased expression of p44/42 mitogen-activated protein kinase (MAPK) (Erk1/2) protein in ABCs harboring mutations in Kras and/or Egfr, confirming the activation of MAPK signaling. Transcriptomic analysis indicated significant alterations in MAPK signaling such as ephrin receptor signaling and signaling by Rho-family GTPases in AT-exposed ABCs. In addition, there was significant overlap between transcriptomic data from mouse ABCs due to AT exposure and human pulmonary adenocarcinoma data. Collectively, these data suggest chronic AT exposure exacerbates MAPK signaling in ABCs and, thus, may be translationally relevant to human lung cancers.

Impaired sensitivity to thyroid hormone correlates to osteoporosis and fractures in euthyroid individuals.

BACKGROUND: There is growing evidence that thyroid function affects bone metabolism and even fractures risk. However, little is known about the relationship between thyroid sensitivity and osteoporosis and fractures. Therefore, we explored the relationship between thyroid sensitivity-related indices and bone mineral density (BMD) and fractures in euthyroid US adults. METHODS: In this cross-sectional study, 20,686 subjects from National Health and Nutrition Examination Survey (NHANES) data were extracted and analyzed during 2007 to 2010. A total of 3403 men and postmenopausal women aged 50 years or older with available data on diagnosis of osteoporosis and/or fragility fractures, bone mineral density (BMD) and thyroid function, were eligible. TSH index (TSHI), thyrotrophin T4/T3 resistance index (TT4RI/TT3RI), Thyroid feedback quantile-based index (TFQI), Parametric TFQI (PTFQI), free triiodothyronine to free thyroxine ratio (FT3/FT4), the secretory capacity of the thyroid gland (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD) were calculated. RESULTS: FT3/FT4, SPINA-GD, FT4, TSHI, TT4RI, TFQI and PTFQIFT4 were significantly correlated with BMD (P < 0.001). Multiple linear regression analysis showed that FT3/FT4 and SPINA-GD was significantly positively associated with BMD, while FT4, TSHI, TT4RI, TFQI and PTFQIFT4 were negatively associated with BMD (P < 0.05 or P < 0.001). In logistic regression analysis, the odds ratio (OR) for osteoporosis of TSHI, TFQI and PTFQIFT4 were 1.314(1.076, 1.605), 1.743(1.327, 2.288) and 1.827(1.359, 2.455) respectively, and were 0.746(0.620, 0.898) for FT3/FT4 (P < 0.05). CONCLUSIONS: In elderly euthyroid individuals, impaired sensitivity to thyroid hormones correlates to osteoporosis and fractures, independent of other conventional risk factors.

[Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI].

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

[Differential diagnosis between pulmonary artery sarcoma and central chronic pulmonary thromboembolism:a preliminary study on CT signs].

Objective: To improve the diagnostic accuracy of pulmonary artery sarcoma, and to distinguish it from central chronic pulmonary thromboembolism using CT scans. Methods: In this retrospective study, two groups of pulmonary artery sarcoma (PAS group) and central chronic pulmonary thromboembolism (central CPTE group) confirmed by pathology at our hospital between August 2009 and July 2019 were enrolled, clinical features and pre-operative CT pulmonary artery manifestation were collected, and the key points of differential diagnosis were summarized. Results: The study was composed of 13 cases in the PAS group including 10 males (76.9%), with an average age of (45.4±15.5) years. There were 19 patients in the central CPTE group including 14 males (73.7%), with an average age of (38.6±14.1) years. There were no significant differences in gender and age between the two groups. Deep venous thrombosis in the lower extremities was significantly higher in the central CPTE group than in the PAS group (7/19 vs. 0/13, P=0.025), and the N-terminal pro-brain natriuretic peptide value was higher in the central CPTE group than in the PAS group [674.50(261.70-1 977.70) vs. 66.00(28.10-505.50),P=0.001]. In CT pulmonary angiography, the involvement of the main pulmonary artery, and the proximal lesion showing an acute angle to the pulmonary artery wall were more common in the PAS group [11(84.6%) vs. 5(26.3%), P=0.003; 11(84.6%) vs. 2(10.5%), P<0.001, respectively]. The swelling index of the main pulmonary and the left/right main pulmonary arteries in the PAS group were significantly higher, as well as the dilatation in the lobar and segmental pulmonary arteries [1.19±0.17 vs. 0.99±0.19,P=0.006, 10(76.9%) vs. 2(10.5%), P<0.001, respectively]. The right ventricular transverse diameter/left ventricular transverse diameter (RVd/LVd) and pulmonary artery diameter/ascending aortic diameter ratio (Pad/Aod) were significantly lower in PAS group than those in the central CPTE group (0.97±0.19 vs. 1.23±0.35,P=0.020; 0.98±0.25 vs. 1.15±0.20,P=0.039). Conclusions: In CT pulmonary angiography, filling defects involving the main pulmonary artery and showing expansive growth were highly suggestive of pulmonary artery sarcoma. The history of deep venous thrombosis of the lower extremities was helpful for the diagnosis of chronic pulmonary embolism.

Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

[Development of a quality of life questionnaire for adults with anisometropic amblyopia].

Objective: To develop and validate the health-related quality of life (HRQOL) questionnaire for adult patients with anisometropic amblyopia. Methods: Cross-sectional study. A total of 170 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 80 healthy adults with normal vision were recruited at the First Affiliated Hospital of Nanjing Medical University, and 20 healthy adults with normal vision were recruited at Qinhuai Medical District of Easter Theater General Hospital of PLA from December 2019 to February 2020. Individual interviews of 30 adult patients with anisometropic amblyopia generated 80 questionnaire items. For item reduction, 40 adult patients with anisometropic amblyopia were asked to complete the 80-item questionnaire and responses were analyzed. Then factor analyses were performed to identify prominent factors (subscales). The reliability of the questionnaire was evaluated by Cronbach's α coefficient. The overall and sub-scale scores were the average scores of all included items, ranging from 0 (worst HRQOL) to 100 (best HRQOL). The final 20-item questionnaire was administered to additional 100 adult patients with anisometropic amblyopia, 100 adult patients with other eye diseases and 100 visually normal adults. Mean overall and subscale scores were compared across groups using one-way analysis of variance. Results: The final adult anisometropic amblyopia questionnaire (AAAQ) consisted of a function subscale and a psychosocial subscale, each containing 10 items. The Cronbach's α coefficients of the overall, function subscale and psychosocial subscale were 0.88, 0.78 and 0.78. There were 55 males and 45 females in 100 adult anisometropic amblyopia patients, with a median age of 26 years (range, 18 to 43 years). The age and gender distribution were matched with 100 adult patients with other eye diseases and 100 healthy adults with normal vision (all P>0.05). The mean overall score (28.63±9.18), function subscale score (27.69±9.88) and psychosocial subscale score (29.53±9.90) for adult patients with anisometropic amblyopia were significantly lower compared to adult patients with other eye diseases (71.28±8.14, P<0.01; 65.56±7.81, P<0.01; 76.85±10.76, P<0.01) and visually normal adults (84.54±9.13, P<0.01; 81.70±9.27, P<0.01; 87.38±10.06, P<0.01). Conclusion: The AAAQ meets the requirements for validity and reliability of a HRQOL questionnaire, and can be used to assess the HRQOL of adult patients with anisometropic amblyopia. (Chin J Ophthalmol, 2021, 57: 341-347).

[Effects of combination of dihydroartemisinin and Huobahua on expression of p-p38 MAPK and ICAM-1 in mice with delayed-type hypersensitivity].

The aim of this paper was to investigate the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in mice with delayed hypersensitivity and explore its possible mechanism. The delayed-type hypersensitivity(DTH) model in mice was established to observe the immunosuppressive effects of dihydroartemisinin and Huobahua compatibility in DTH mice. ELISA assay was used to detect the contents of interferon(IFN-γ); histopathological changes and degree of mononuclear infiltration of right ear tissues were examined by HE staining; the expression level of intercellular cell adhesion molecule-1(ICAM-1) in the right ear of mice was detected by immunohistochemistry; the protein expression levels of p38 phospho mitogen activated protein kinase(p-p38 MAPK) was detected by Western blot analysis. As compared with the control group, the degree of ear swelling, thymus/spleen index, serum IFN-γ as well as the number and degree of infiltration of monocytes were significantly increased in the model group. As compared with the model group, the degree of ear swelling and thymus/spleen index of the mice in the combination group were significantly reduced; the number and degree of infiltration of monocytes were significantly relieved; the serum levels of IFN-γ and the expression levels of p-p38 MAPK and ICAM-1 proteins in the right ear were also significantly reduced. The combination of dihydroartemisinin and Huobahua can significantly inhibit the DTH response, and it may regulate the production and secretion of related inflammatory factor IFN-γ by inhibiting the phosphorylation activity of p38 MAPK, thereby further reducing the expression of ICAM-1 and thus exerting the immunosuppressive effect.

High Serum Neuron-Specific Enolase (NSE) Level Firstly Ignored as Normal Reaction in a Small Cell Lung Cancer Patient: a Case Report and Literature Review.

BACKGROUND: High serum neuron-specific enolase (NSE) level has been in use as a tumor marker; however, some physicians may ignore NSE levels in serum, especially when the patients are asymptomatic. Here we report a case that a 51 year old female patient with no respiratory symptoms who had a NSE level which increased extremely over three months and was eventually diagnosed small cell lung cancer (SCLC). METHODS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in right pulmonary hilar enlarged lymph node was performed for diagnosis. RESULTS: EBUS showed right pulmonary hilar lymph node enlargement. A TBNA biopsy histopathology diagnosed SCLC. CONCLUSIONS: We should pay attention to high serum NSE levels, especially when the index increased extremely over a short time.

Tuberculosis Antibody and Tuberculin Positive Tests Initially Misdiagnosed as Active Tuberculosis in a Broncholithiasis Patient with Recurrent Hemoptysis and Fever Proven by Lung Lobectomy.

BACKGROUND: To report a case of broncholithiasis with recurrent hemoptysis and fever initially misdiagnosed as active tuberculosis. METHODS: The chest contrast-enhanced CT scan, electronic bronchoscope, and ultrathin bronchoscope were performed leading to the diagnosis of broncholithiasis, open lung lobectomy was done after thoracic surgery consultation. RESULTS: The chest contrast-enhanced CT scan showed a high-density intratracheal shadow and calcified lymph nodes. Ultrathin bronchoscopy manifested calcified lesions located at the distal portion of the right lower lobe bronchus. Histopathology of lobectomy showed lithiasis in the right lower lobe tracheobronchial tree. CONCLUSIONS: We should pay attention to calcified intratracheal lesions and make differential diagnosis with tuberculosis, especially when accompanied with calcified lymph nodes and fever.

Elevated Plasma D-Dimer in Adult Community-Acquired Pneumonia Patients is Associated with an Increased Inflammatory Reaction and Lower Survival.

BACKGROUND: Community-acquired pneumonia (CAP) is a common infectious disease. Inflammatory reaction and prognosis assessment in adult CAP patients are useful for CAP site of care decisions. Most CAP patients were diagnosed in an out-patient or emergency department, so a simple, cheap and rapidly available measurement to assess inflammatory reaction and prognosis has the prospect of broad application. The aim of this study was to investigate the usefulness of plasma D-Dimer in assessment of inflammatory reaction and prognosis in adult CAP patients. METHODS: A retrospective study was conducted. All adult patients with a primary diagnosis of CAP were included and were evaluated by peripheral plasma D-Dimer test. All of the measurement data were analyzed with paired t-test and the enumeration data were analyzed with χ2 test. Correlative factor analysis was performed between D-Dimer levels and serum inflammatory markers (WBC, hs-CRP, PCT) and prognostic indexes (ICU admission and 30-day mortality). Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of D-Dimer in predicting ICU admission and/or 30-day mortality. RESULTS: One hundred fifty patients were included. Compared with non-D-Dimer elevated group, serum inflammatory markers (WBC, hs-CRP, PCT) and prognostic indexes (ICU admission and 30-day mortality) were elevated in the D-Dimer elevated group (p < 0.05). D-Dimer had positive correlation with serum inflammatory markers (WBC, hs-CRP, PCT), the rates of ICU admission and 30-day mortality, and scores of CURB-65. The AUC of ROC curve of D-Dimer was 0.880 (95% CI 0.823 to 0.936), the sensitivity was 80.4% and specificity was 79.8%, D-Dimer levels are superior to hs-CRP and PCT in predicting 30-day mortality and/or ICU admission according to AUCs of the ROC curves. CONCLUSIONS: Elevated plasma D-Dimer in adult CAP patients is associated with an increased inflammatory reaction and ICU admission and 30-day mortality. It can be a simple, cheap, and rapidly available measurement to assess inflammatory reaction and prognosis in adult CAP patients.

Persistent Anemia Combined Increased Serum Sedimentation (ESR) for More Than Two Years Firstly Misdiagnosed as Lymphoma Ultimately Confirmed Systemic Lymph Nodes Tuberculosis by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Pathology: a Case Report and Literature Review.

BACKGROUND: Anemia combined with increased serum sedimentation (ESR) can be secondary to many diseases and may be ignored when the patient had few clinical symptoms. We report a case of persistent anemia combined with ESR for more than 2 years firstly misdiagnosed as lymphoma. When she received a chest CT scan multiple enlarged lymph nodes were found. METHODS: The chest contrast-enhanced CT scan and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the right hilum enlarged lymph nodes were performed for diagnosis. RESULTS: The chest CT scan and EBUS showed multiple enlarged right hilum and mediastinum lymph nodes without calcification. Pathology of EBUS-TBNA showed multiple granulomas; Zeihl-Neelsen acid-fast stain was positive. CONCLUSIONS: Systemic lymph node tuberculosis is rarely seen in adult patients. In a young patient who has anemia combined with increased ESR should be excluded if those changes are secondary to tuberculosis.

Elevated Red Blood Cell Distribution Width Combined White Blood Cell in Peripheral Blood Routine Have a Better Sensitivity than CURB-65 Scores in Predicting ICU Admission and Mortality in Adult Community-Acquired Pneumonia Patients.

Background: Scoring systems including CURB-65 and Pneumonia Severity Index (PSI) and novel or traditional biomarkers including procalcitonin (PCT) and c-reactive protein (CRP) are very significant for understanding the severity and prognosis in community-acquired pneumonia (CAP) patients, while prognostic items are useful for CAP prognostication and point-of-care decisions. The aim of this study was to investigate the usefulness of peripheral blood routine items in predicting ICU admission and 30-day mortality in CAP patients.

Methods: A retrospective study was conducted. All adult patients with a primary diagnosis of CAP were included and peripheral blood routine tests were evaluated. Univariate analysis and multivariate logistic regression analysis were used to explore association of risk factors with 30-day mortality among CAP patients. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of peripheral blood routine items and compared with CURB-65 scores in predicting ICU admission and/or 30-day mortality.

Results: One hundred fifty patients were included and compared with non-ICU admission patients. There was a statistically significant difference in age, co-existing illness, RDW, WBC, and CURB-65 scores ranking in ICU admission patients (p < 0.05). In multivariate logistic regression analysis, we found RDW, WBC, and CURB-65 ≥ 3 scores increased the risk of 30-day mortality by 4.01, 1.65, and 3.43 times, respectively. The area under the curve (AUC) of ROC curves of RDW combined with WBC and CURB-65 was 0.786 (95% CI 0.701 to 0.876) and 0.836 (95% CI 0.764 to 0.908), respectively and the sensitivity was 84.0% and 60.0%, respectively, and the specificity 66.7% and 93.7%, respectively.

Conclusions: Elevated RDW and WBC increased mortality in adult CAP patients, RDW combined with WBC had a better sensitivity than CURB-65 scores in predicting ICU admission and/or mortality in CAP patients.

Neutrophil-to-Lymphocyte Ratio Improves the Accuracy and Sensitivity of Pneumonia Severity Index in Predicting 30-Day Mortality of CAP Patients.

BACKGROUND: The pneumonia severity index (PSI) scoring system is one of the tools used to evaluate and predict the prognosis of patients with community-acquired pneumonia (CAP). Although PSI has been widely used in clinical studies of pneumonia, it is still rare to combine it with blood indexes to predict the prognosis of pneumonia. Neutrophil-to-lymphocyte ratio (NLR) is a promising candidate predictor of mortality in CAP patients. The aim of this study was to investigate the efficacy of pneumonia severity index combined with NLR in predicting 30-day mortality in CAP patients. METHODS: We conducted a retrospective study. We analyzed data on 400 non-immune individuals over the age of 18 in this study. All patients received blood routine measurement and PSI score calculation after admission. The primary outcome measures were mortality and survival in CAP patients. The sensitivity and specificity of PSI score, NLR, and the combination of PSI score and NLR in predicting 30-day mortality were assessed using the subject operating characteristic curve (ROC). RESULTS: Data from 400 patients were analyzed, in which the 30-day mortality was 10.5% (42/400). The AUC of NLR and PSI in predicting 30-day mortality of CAP patients were 0.81 (95% CI 0.73 - 0.89) and 0.94 (95% CI 0.90 - 0.98), respectively, with statistically significant differences (p = 0.00). The sensitivity and specificity of NLR were 0.80 and 0.7, respectively. The sensitivity and specificity of PSI were 0.78 and 0.94, respectively. The combined AUC of the two indicators for predicting death in CAP patients was 0.95 (95% CI 0.92 - 0.99), and the sensitivity and specificity were 0.85 and 0.94, respectively. CONCLUSIONS: Neutrophil-to-lymphocyte ratio improves the accuracy and sensitivity of the pneumonia severity index in predicting 30-day mortality of CAP patients.

Alterations in the intestinal microbiota of patients with severe and active Graves' orbitopathy: a cross-sectional study.

BACKGROUND: The intestinal microbiota was linked to autoimmune diseases. Graves' orbitopathy (GO) is an autoimmune disease that is usually associated with Graves' disease. However, information on the microbiome of GO patients is yet lacking. OBJECTIVES: To investigate whether GO patients differ from healthy controls in the fecal microbiota. DESIGN: A cross-sectional study. SETTING: 33 patients with severe and active GO and 32 healthy controls of Han nationality were enrolled between March 2017 and March 2018. METHODS: The Gut microbial communities of the fecal samples of GO patients and healthy controls were analyzed and compared by 16S rRNA gene sequencing. RESULTS: Community diversity (Simpson and Shannon) was significantly reduced in fecal samples from patients with GO as compared to controls (p < 0.05). The similarity observed while assessing the community diversity (PCoA) proposed that the microbiota of patients with GO differ significantly from those of controls (p < 0.05). At the phyla levels, the proportion of Bacteroidetes increased significantly in patients with GO (p < 0.05), while at the genus and species levels, significant differences were observed in the bacterial profiles between the two groups (p < 0.05). LIMITATIONS: Single-centered study design and limited fecal samples. CONCLUSIONS: The present study indicated distinctive features of the gut microbiota in GO patients. The study provided evidence for further exploration in the field of intestinal microbiota with respect to the diagnosis and treatment of GO patients by modifying the microbiota profile.

[Relationship between SHP-1 gene methylation and STAT3 phosphorylation and prognosis in patients with myelodysplastic syndrome].

Objective: To assess the methylation level of SHP-1 promoter region and the effects on the phosphorylation of the Signal Transducers and Activators of Transcription 3 (STAT3) protein in bone marrow specimen of patients with myelodysplastic syndrome (MDS), and to explore the relationship of SHP-1 methylation and prognosis of the patients. Method: Bone marrow specimens of 93 patients with MDS were collected from the General Hospital of Tianjin Medical University from September 2010 to June 2014. The enrolled subjects included 54 males and 39 females and they were divided into the low-risk group (IPSS score:0-1.0, median: 0.5) and the high-risk group (IPSS score: 1.5-3.0, median: 2.5) according to the International Prognostic Score System (IPSS). The methylation level of SHP-1 was detected by methylation-specific polymerase chain reaction, and the level of p-STAT3 was detected using Western blot. Results: In the high-risk group, 64.44% (29/45) of the patients had methylation in the SHP-1 promoter region, which was significantly higher than the low-risk group 22.92% (11/48). Therefore, SHP-1 methylation was frequently presented in the patients of the high-risk group. Similarly, 66.67% (30/45) of the patients in the high-risk group had positive STAT3 phosphorylation status, whereas only 20.83% (10/48) were tested positive in the low-risk group. In addition, correlation analysis also revealed that the SHP-1 methylation rate was positively correlated with the positive rate of STAT3 phosphorylation (r=0.57,P<0.001). Conclusions: SHP-1 methylation is significantly correlated with the risk of MDS patients. It may be used as an independent predictor of shorter survival in patients of the high-risk group. The increased level of SHP-1 methylation will lead to the uncontrolled activation of the downstream JAK/STAT3 pathway, which in turn can cause further positive feedback to amplify the carcinogenic signal.

Pulmonary thromboendarterectomy is a curative resolution for chronic thromboembolic pulmonary hypertension associated with antiphospholipid syndrome: a retrospective cohort study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening condition with poor prognosis in patients with antiphospholipid syndrome (APS). Pulmonary thromboendarterectomy (PTE) is the optimal surgical option for CTEPH. OBJECTIVES: This retrospective cohort study aimed to evaluate the efficacy and risk of PTE in patients with APS-associated CTEPH. METHODS: Consecutive patients with APS-associated CTEPH diagnosed between January 2012 and September 2017 at Peking Union Medical College Hospital were retrospectively evaluated. Demographics, clinical manifestations, antiphospholipid antibody (aPL) profiles, and pulmonary arterial hypertension-targeted medications were collected. Deterioration of cardiac function and death were chosen as the endpoints, in order to assess the effect of PTE on short-term and long-term prognoses (evaluated by the change of cardiac function after treatment and cardiac deterioration or death in the follow-up, respectively). RESULTS: A total of 20 patients with APS-associated CTEPH were enrolled, and eight patients underwent PTE. Chi-square test ( p = 0.01) and Kaplan-Meier curves (log rank test, p = 0.04) showed that there were statistically significant differences in both short-term and long-term prognoses between patients with and without PTE. CONCLUSION: These results provide strong evidence that PTE is a curative resolution in patients with APS-associated CTEPH. Following a full specialized and multidisciplinary risk-benefit evaluation to limit the risk of thrombosis or bleeding and to manage possible thrombocytopenia, PTE is at least a temporal curative resolution for CTEPH complicated with APS.

Exome Sequencing of Fresh-frozen or Formalin-fixed Paraffin-embedded B6C3F1/N Mouse Hepatocellular Carcinomas Arising Either Spontaneously or due to Chronic Chemical Exposure.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide; however, the mutational properties of HCC-associated carcinogens remain largely uncharacterized. We hypothesized that mechanisms underlying chemical-induced HCC can be characterized by evaluating the mutational spectra of these tumors. To test this hypothesis, we performed exome sequencing of B6C3F1/N HCCs that arose either spontaneously in vehicle controls ( n = 3) or due to chronic exposure to gingko biloba extract (GBE; n = 4) or methyleugenol (MEG; n = 3). Most archived tumor samples are available as formalin-fixed paraffin-embedded (FFPE) blocks, rather than fresh-frozen (FF) samples; hence, exome sequencing from paired FF and FFPE samples was compared. FF and FFPE samples showed 63% to 70% mutation concordance. Multiple known (e.g., Ctnnb1T41A, BrafV637E) and novel (e.g., Erbb4C559S, Card10A700V, and Klf11P358L) mutations in cancer-related genes were identified. The overall mutational burden was greater for MEG than for GBE or spontaneous HCC samples. To characterize the mutagenic mechanisms, we analyzed the mutational spectra in the HCCs according to their trinucleotide motifs. The MEG tumors clustered closest to Catalogue of Somatic Mutations in Cancer signatures 4 and 24, which are, respectively, associated with benzo(a)pyrene- and aflatoxin-induced HCCs in humans. These results establish a novel approach for classifying liver carcinogens and understanding the mechanisms of hepatocellular carcinogenesis.

Does Adenovirus and Coxsackie B Virus Infection Play a Role in Tracheobronchopathia Osteochondroplastica (TO).

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disease. We report a case of TO. Methods: Chest CT scan and bronchoscope with biopsy was performed for diagnosis and blood tests explored for the latent etiology. Results: Chest CT scan and bronchoscopic images showed multiple nodular protrusions in the trachea and main bronchi. Histopathology demonstrated sub-mucosal ossification and inflammatory cell infiltration. Laboratory inspection showed adenovirus and coxsackie B virus IgM antibodies were positive. Conclusions: The patient recently had a virus infection and inflammation was observed in histopathology, which indicated adenovirus and coxsackie B virus may play a role in the occurrence or exacerbation of TO.