Associations of combined phenotypic ageing and genetic risk with incidence of chronic respiratory diseases in the UK Biobank: a prospective cohort study.

BACKGROUND: Accelerated biological ageing has been associated with an increased risk of several chronic respiratory diseases. However, the associations between phenotypic age, a new biological age indicator based on clinical chemistry biomarkers, and common chronic respiratory diseases have not been evaluated. METHODS: We analysed data from 308 592 participants at baseline in the UK Biobank. The phenotypic age was calculated from chronological age and nine clinical chemistry biomarkers, including albumin, alkaline phosphatase, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red cell distribution width and white blood cell count. Furthermore, phenotypic age acceleration (PhenoAgeAccel) was calculated by regressing phenotypic age on chronological age. The associations of PhenoAgeAccel with incident common chronic respiratory diseases and cross-sectional lung function were investigated. Moreover, we constructed polygenic risk scores and evaluated whether PhenoAgeAccel modified the effect of genetic susceptibility on chronic respiratory diseases and lung function. RESULTS: The results showed significant associations of PhenoAgeAccel with increased risk of idiopathic pulmonary fibrosis (IPF) (hazard ratio (HR) 1.52, 95% CI 1.45-1.59), COPD (HR 1.54, 95% CI 1.51-1.57) and asthma (HR 1.18, 95% CI 1.15-1.20) per 5-year increase and decreased lung function. There was an additive interaction between PhenoAgeAccel and the genetic risk for IPF and COPD. Participants with high genetic risk and who were biologically older had the highest risk of incident IPF (HR 5.24, 95% CI 3.91-7.02), COPD (HR 2.99, 95% CI 2.66-3.36) and asthma (HR 2.07, 95% CI 1.86-2.31). Mediation analysis indicated that PhenoAgeAccel could mediate 10∼20% of the associations between smoking and chronic respiratory diseases, while ∼10% of the associations between particulate matter with aerodynamic diameter <2.5 µm and the disorders were mediated by PhenoAgeAccel. CONCLUSION: PhenoAgeAccel was significantly associated with incident risk of common chronic respiratory diseases and decreased lung function and could serve as a novel clinical biomarker.

Regional anesthesia might reduce recurrence and metastasis rates in adult patients with cancers after surgery: a meta-analysis.

BACKGROUND: The influence of anesthesia techniques on cancer recurrence and metastasis following oncological surgery is a topic of growing interest. This meta-analysis investigates the potential effects of regional anesthesia (RA), either independently or combined with general anesthesia (GA), on these outcomes. METHODS: We performed an extensive search across PubMed, Embase, and the Cochrane Library databases. The primary outcome was cancer recurrence, while the secondary outcomes were local recurrence and distant metastasis. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by utilizing random-effects models. The Newcastle-Ottawa Scale (NOS) was used for quality assessment of observational studies, the Cochrane Risk of Bias Tool for Randomized Trials (Rob 2.0) was used for randomized controlled trials, and all the outcomes were assessed by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: This study included 32 studies comprising 24,724 cancer patients. RA, either alone or in combination with GA, was significantly associated with reduced cancer recurrence compared to GA alone (OR = 0.82; 95% CI = 0.72 to 0.94; p < 0.01). This association remained significant for prostate cancer patients in subgroup analyses (OR = 0.71; 95% CI = 0.51 to 0.98; p = 0.04) and in the context of epidural anesthesia combined with GA. However, there were no significant associations noted for local recurrence or distant metastasis. CONCLUSIONS: This meta-analysis provides evidence that RA, used alone or adjunctively with GA, is associated with a lower risk of cancer recurrence, particularly in patients with prostate cancer. However, no significant effects were observed on local recurrence or distant metastasis. Further prospective studies should be conducted to clarify this important issue.

Respiratory traits and coal workers' pneumoconiosis: Mendelian randomisation and association analysis.

OBJECTIVES: Susceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker's pneumoconiosis (CWP) in recent studies. However, only a few genes and loci were targeted in previous studies. METHODS: To systematically evaluate the genetic associations between CWP and other respiratory traits, we reviewed the reported genome-wide association study loci of five respiratory traits and then conducted a Mendelian randomisation study and a two-stage genetic association study. RESULTS: Interestingly, we found that for each SD unit, higher lung function was associated with a 66% lower risk of CWP (OR=0.34, 95% CI: 0.15 to 0.77, p=0.010) using conventional Mendelian randomisation analysis (inverse variance weighted method). Moreover, we found susceptibility loci of interstitial lung disease (rs2609255, OR=1.29, p=1.61×10-4) and lung function (rs4651005, OR=1.39, p=1.62×10-3; rs985256, OR=0.73, p=8.24×10-4 and rs6539952, OR=1.28, p=4.32×10-4) were also significantly associated with the risk of CWP. Functional annotation showed these variants were significantly associated with the expression of FAM13A (rs2609255, p=7.4 ×10-4), ANGPTL1 (rs4651005, p=5.4 ×10-7), SPATS2L (rs985256, p=1.1 ×10-5) and RP11-463O9.9 (rs6539952, p=7.1 ×10-6) in normal lung tissues, which were related to autophagy pathway simultaneously according to enrichment analysis. CONCLUSIONS: These results provided a deeper understanding of the genetic predisposition basis of CWP.

Surfactant protein D is associated with 3-month mortality of anti-MDA5 antibody-interstitial lung disease.

OBJECTIVES: To investigate the associations between serum levels of matrix metalloproteinase 7 (MMP7), surfactant protein D (SPD), interleukin 18 (IL-18) and chemokine ligand 18 (CCL18) with dermatomyositis and polymyositis-associated interstitial lung disease (DM/PM-ILD) and evaluate their prognostic values in the disease. METHODS: Seventy-eight patients with multiple disciplinary team diagnosis of DM/PM-ILD were enrolled and classified as anti-melanoma differentiation-associated protein 5 antibody (MDA5)-ILD, anti-synthetase antibodies (ARS)-ILD and other antibodies-ILD upon autoantibodies profiles. Clinical data were collected and serum levels of four biomarkers were analysed. The primary endpoint was 3-month mortality. The cut-off values of biomarkers for mortality were figured out by receiver operating characteristic (ROC) analysis. Cox regression was performed to evaluate predictive values. RESULTS: Serum levels of MMP7 (p=0.036), SPD (p<0.001), IL-18 (p<0.001) and CCL18 (p<0.001) in patients with DM/PM-ILD were significantly higher than healthy controls with levels of MMP7 (p=0.029) and SPD (p=0.029) in patients with MDA5-ILD significantly lower than patients with ARS-ILD. The 3-month mortality in MDA5-ILD was 54.5% (12/22). Multivariate analysis showed that age (p=0.001, HR 1.151, 95% CI 1.063-1.247) and an increased level of SPD (>75.90ng/ml, p=0.005, HR 16.411, 95% CI 2.369-113.711) were significant predictors for 3-month mortality in patients with MDA5-ILD. CONCLUSIONS: Elevated serum biomarkers were associated with DM/PM-ILD with differential levels between MDA5-ILD and ARS-ILD. Age and an increased SPD had prognostic values for predicting short-term mortality in patients with MDA5-ILD. Our study was important in providing a clue for understanding the classification and prognosis of DM/PM-ILD.

A long-term retrospective study of patients with biopsy-proven cryptogenic organizing pneumonia.

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.

Identification of HLA-A2-restricted immunogenic peptides derived from Vitamin D-Binding Protein.

T-cell-mediated destruction of pancreatic ß cells leads to Type 1 diabetes (TID). Vitamin D-Binding Protein (VDBP) has been identified as an autoantigen and T cell reactivity against VDBP increases in the development of T1D. Autoreactive cytotoxic T lymphocytes (CTLs) recognize ß-cell-derived peptides in the context of major histocompatibility complex class I molecules. However, little is known about the VDBP-derived immunogenic peptides that are presented in the context of human HLA molecules. Here, we predicted and identified VDBP derived immunogenic peptides that were presented in association with human HLA-A2 molecule. The VDBP derived peptides binding to HLA-A∗0201 were predicted by using a computer-assisted algorithm. The candidate peptides were synthesized, then affinity between peptides and HLA-A∗0201 were analyzed. In addition, the CTL activity of the peptides was detected by cytotoxicity assay and ELISPOT assay in vitro. Furthermore, HLA-A∗0201-transgenic mice were immunized with peptides to induce the CTL activity in vivo. The results demonstrated that peptides of VDBP containing residues 211-219 and 235-243 had high affinity with HLA-A∗0201. In addition, these peptides elicited potent CTL responses in vitro, and induced T1D in vivo. Therefore, this experiment identified immunogenic HLA-A∗0201-restricted epitopes derived from VDBP, and provided pathogenesis theory of T1D.

Diffuse parenchymal pulmonary amyloidosis associated with multiple myeloma: a case report and systematic review of the literature.

BACKGROUND: Pulmonary is an uncommon site of extramedullary involvement in multiple myeloma (MM). Diffuse parenchymal amyloidosis as pulmonary manifestation of MM is even rarer. We report a rare case of diffuse parenchymal pulmonary amyloidosis associated with MM diagnosed by video-assisted thoracoscopic lung biopsy (VATLB). CASE PRESENTATION: A 58-year-old woman complained of cough and shortness of breath. HRCT disclosed diffuse ground-glass opacifications with interlobular septal thickening in bilateral lungs. A lung-biopsy sample obtained by VATLB revealed Congo Red-positive amorphous eosinophilic deposits in the alveolar septa. Surgical biopsy of abdominal wall skin and subcutaneous fat was also performed, which showed the apple-green birefringence with polarized light on Congo red stain was demonstrated in dermis. The serum immunoelectrophoresis showed monoclonal lambda light chains. A bone marrow biopsy specimen comprised 11.5% plasma cells. She was therefore diagnosed with diffuse parenchymal pulmonary amyloidosis accompanied by MM. The patient was referred to the hematology department for further chemotherapy. CONCLUSIONS: It is important to recognize diffuse parenchymal pulmonary amyloidosis to avoid misdiagnosis.

Application of controlled hypotension in cesarean section of pregnant women with high-risk hemorrhage.

To explore the application of controlled hypotension in cesarean section of pregnant women with high-risk hemorrhage. 75 cases were randomly divided into three groups: controlled hypotension Group 1 (Group H1), controlled hypotension Group 2 (Group H2) and normal blood pressure Group (Group N). The preoperative general data, intraoperative conditions, postpartum concurrent Symptoms and other indicators of all the cases in three groups were compared. The Apgar score, umbilical arterial blood gas and other indicators of the newborns were detected. There was no significant difference in the preoperative general data, Apgar score at 1 min and 5 min, the level of PH, PaO2, PaCO2 among the three groups (P>0.05). The intraoperative blood transfusion volume in group H1 and group H2 decreased significantly than that in group N (P<0.05), but there was no significant difference between group H1 and group H2 (P>0.05). Compared with group H1, the red cell transfusion volume in group H2 was significantly reduced (P<0.05). There was no significant difference in other intra-operative indexes such as bleeding volume, infusion volume, patient urine volume and hospitalization days among the three groups (P>0.05). Controlled hypotension (within 5 min of MAP down to 70% of basal blood pressure) can reduce the incidence of hemorrhage and postpartum hemorrhage during cesarean section in high-risk bleeding pregnant women and which had no bad effects on the incidence of complications and umbilical arterial blood gas indicators compared with control group.

A novel mimovirus encoding ChgA10-19 peptide with PD-L1 induces T cell tolerance and ameliorates the severity of diabetes.

Related studies demonstrate that type 1 diabetes (T1D) is caused by ß-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD.ß2m null HHD mice were administrated with mimovirus transduced DCs. After immunization, the activation and proliferation of CD8+ T cells were detected, diabetes incidence and pancreatic tissue destruction were also analyzed. The results demonstrated that transduced DCs attenuated CD8+ T cell activation and proliferation. In addition, transduced DCs inhibited CD8+ T response to ChgA stimulation, and ameliorated the severity of diabetes. These data suggested that mimovirus transduced DCs might provide novel clues for T1D therapy.

Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3ß Pathway.

The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3ß (p-GSK-3ß) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3ß inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3ß-dependent mechanism.

Pentoxifylline Ameliorates Cardiac Fibrosis, Pathological Hypertrophy, and Cardiac Dysfunction in Angiotensin II-induced Hypertensive Rats.

Inflammation induces cardiac fibrosis and hypertrophy in multiple cardiovascular diseases, contributing to cardiac dysfunction. We tested the hypothesis that pentoxifylline (PTX), a phosphodiesterase inhibitor with anti-inflammatory property, would attenuate cardiac fibrosis and hypertrophy, and prevent cardiac dysfunction in angiotensin (ANG) II-induced hypertensive rats. Sprague-Dawley rats were divided into control and ANG II-infused groups treated with or without PTX for 2 weeks. PTX had no effect on ANG II-induced hypertension, but significantly attenuated cardiac fibrosis and hypertrophy, and ameliorated cardiac dysfunction in ANG II-induced hypertensive rats. In addition, ANG II-induced increase in circulating and cardiac proinflammatory cytokines were attenuated by PTX, which reduced cardiac nuclear factor-kappa B activity. Furthermore, PTX decreased cardiac expression of genetic markers important for fibrosis, hypertrophy, and endothelial dysfunction, and reduced migration and infiltration of macrophages. In contrast, PTX had no effects on the above parameters in control rats. The findings suggest that PTX ameliorates cardiac fibrosis, pathological hypertrophy, and cardiac dysfunction by suppressing inflammatory responses in angiotensin II-induced hypertension, and that these benefits were independent of the blood pressure lowering effect. The PTX by its anti-inflammatory property may be a potential therapeutic option for the prevention of cardiac remodeling and dysfunction in ANG II-induced hypertension.

Adsorption of Vanadium (V) from SCR Catalyst Leaching Solution and Application in Methyl Orange.

In this study, we explored an effective and low-cost catalyst and its adsorption capacity and catalytic capacity for Methyl Orange Fenton oxidation degradation were investigated. The catalyst was directly prepared by reuse of magnetic iron oxide (Fe3O4) after saturated adsorption of vanadium (V) from waste SCR (Selective Catalytic Reduction) catalyst. The obtained catalyst was characterized by FTIR, XPS and the results showed that vanadium (V) adsorption process of Fe3O4 nanoparticles was non-redox reaction. The effects of pH, adsorption kinetics and equilibrium isotherms of adsorption were assessed. Adsorption of vanadium (V) ions by Fe3O4 nanoparticles could be well described by the Sips isotherm model which controlled by the mixed surface reaction and diffusion (MSRDC) adsorption kinetic model. The results show that vanadium (V) was mainly adsorbed on external surface of the Fe3O4 nanoparticles. The separation-recovering tungsten (VI) and vanadium (V) from waste SCR catalyst alkaline solution through pH adjustment was also investigated in this study. The results obtained from the experiments indicated that tungsten (VI) was selectively adsorbed from vanadium (V)/tungsten (VI) mixed solution in certain acidic condition by Fe3O4 nanoparticle to realize their recovery. Tungsten (V) with some impurity can be obtained by releasing from adsorbent, which can be confirmed by ICP-AES. The Methyl Orange degradation catalytic performance illustrated that the catalyst could improve Fenton reaction effectively at pH = 3.0 compare to Fe3O4 nanoparticles alone. Therefore, Fe3O4 nanoparticle adsorbed vanadium (V) has a potential to be employed as a heterogeneous Fenton-like catalyst in the present contribution, and its catalytic activity was mainly evaluated in terms of the decoloration efficiency of Methyl Orange.

[Clinical and high-resolution computed tomography characteristics of the welder's pneumoconiosis].

OBJECTIVE: To investigate the clinical and high-resolution computed tomography (HRCT) features of the welder's pneumoconiosis. METHODS: A total of 10 patients diagnosed by bronchoscopy and pathology from January 2010 to January 2015 in Nanjing Drum Tower Hospital were recruited in this study, and the clinical manifestations, pulmonary function tests, pathology and HRCT data were collected and analyzed retrospectively. RESULTS: Ten patients all had welder's occupational history for 5-30 years, with the main clinical manifestations of cough, sputum production, chest tightness and other symptoms. And the ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) of 4 patients was lower than 75.0% in the pulmonary function tests. Transbronchial lung biopsy specimen showed numerous hemosiderin-laden macrophages within the alveolar space, associated with positive iron staining. In welder's pneumoconiosis, small centrilobular nodules (10 cases) were frequently seen on HRCT in bilateral lung fields, with branching linear structures or the tree buds like shadows in 7 cases; 3 patients also showed areas of ground-glass attenuation. And the patients were misdiagnosed as tuberculosis (1/10), interstitial pneumonia (3/10), allergic alveolitis (1/10), diffuse lung disease (2/10), and vasculitis (1/10). CONCLUSIONS: Clinical manifestations of welder's pneumoconiosis are not specific; small centrilobular nodules are frequently seen on HRCT, with linear opacities or tree bud-like shadows.

[Analysis for differences in clinical and radiologic findings between patients with cryptogenic organizing pneumonia and connective tissue disorder related organizing pneumonia].

OBJECTIVE: To investigate the difference in clinical features and radiologic findings between patients with cryptogenic organizing pneumonia (COP) and connective tissue disorder related organizing pneumonia (CTD-OP). METHODS: A total of 30 subjects with COP and 22 subjects with CTD-OP collected from 2005 to 2013 were retrospectively reviewed in the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, and the diagnosis of all patients were confirmed by lung biopsy. RESULTS: The common underlying diseases in patients with CTD-OP were Sjogren syndrome(SS), poly-/dermatomyositis(PM/DM), rheumatoid arthritis (RA). There were no significant differences in clinical manifestations between CTD-OP and COP. Compared with COP patients, the proportion of female patients was higher in CTD-OP. Higher positive rate for ANA was found in CTD-OP group (CTD-OP:63.6%; COP:10.0%; P<0.01). There were no significant differences in parameters of lung function between CTD-OP and COP. As to radiological findings, the most common patterns were multiple patchy, linear shadows and ground-glass opacity. Some patients showed solitary nodule or consolidation and pleural effusion. Reticular shadow was a rare pattern among these patients. Most lesions were under the pleura and/or around the bronchus. CONCLUSIONS: There are no significant differences in clinical and radiologic manifestations between COP and CTD-OP, except that the proportion of women and ANA positive rate were higher in CTD-OP.

[HER2 protein testing in gastric cancer: a retrospective analysis of 1 471 cases during two different periods in a single medical center].

OBJECTIVE: To study the potential factors in influencing the performance of immunohistochemical testing for HER2 protein in gastric cancers. METHODS: The HER2 protein expression status of 1 471 surgically resected archival gastric cancer cases in Drum Tower Hospital collected during two different periods was retrospectively analyzed. The materials included 957 cases tested during the period from 2007 to 2009 (group 1) and 514 cases from 2012 to 2013 (group 2). The test procedures and results observed during these two periods were compared. RESULTS: The percentages of score 3 HER2 protein expression (14.4%, 74/514 versus 9.5%, 91/957) and score 2 or score 3 HER2 protein expression (27.2%, 140/514 versus 21.7%, 208/957) were both higher in group 2 than in group 1 (P < 0.05). In group 1, the cancer tissue was fixed in 10% formalin, stained manually with HER2 antibody A0485 (Dako) and assessed by different pathologists.In group 2, the tissue was fixed in 10% neutral buffered formalin (pH 7.2), stained using automated immunostaining system (Roche Benchmark XT) with HER2 antibody 4B5 (Ventana) and assessed by a specialized team of pathologists. CONCLUSION: The results of HER2 immunostaining in gastric cancer are influenced by a number of factors including type of fixative, clone number of primary antibody, staining methods and experience of pathologists.

[Primary hyperparathyroidism with metastatic pulmonary calcification: a case report and review of literature].

OBJECTIVE: To highlight the characteristics of metastatic pulmonary calcification(MPC) of a patient with primary hyperparathyroidism. METHODS: The clinical, radiological, pathological and (99)mTc-MDP bone scanning data of the patient with primary hyperparathyroidism were studied and relevant literature was reviewed. RESULTS: This 56 year-old female patient presented with cough and shortness of breath. The chest CT scan showed multiple, bilateral infiltrates and calcification in the left lung and ventricular wall. Transbronchial lung biopsy was performed, and the pathological study showed that there was diffuse calcification in the alveoli and alveolar septa.(99)mTc-MDP bone-scanning showed pulmonary uptake mostly. The patient showed significant clinical and radiological improvement after surgical removal of the parathyroid gland. CONCLUSIONS: Patients of primary hyperparathyroidism with respiratory symptoms were easily misdiagnosed as primary pulmonary diseases.(99)mTc-MDP bone-scanning can be used to help differentiate MPC from other diseases with similar clinical and radiological findings, thus allowing prompt therapy.

Bronchial Basaloid Papillary Tumor of Uncertain Malignant Potential: A Case Report.

Bronchial papillomas are benign tumors, which can be divided into different subtypes based on the cellular features. So far, no bronchial papilloma with basaloid cell features has been reported. We report a bronchial basaloid papillary tumor in a 67-year-old woman. Tumor recurrence and malignant transformation were observed after a long-term follow-up. The clinical, histological, immunohistochemical, and genetic features were reappraised. The primary tumor was characterized by papillary growth pattern and basaloid neoplastic cells, only a small amount of neoplastic cells showed mature characteristics. The tumor originated from respiratory epithelium and had a low proliferation index by Ki-67. Keratin (KRT) 5/6 and KRT7 showed patchy or partial positivity. Myoepithelial markers were negative. P63 was diffusely positive, but it was negative in the small amount of tumor cells with mature characteristics. The common genetic alterations (EGFR, KRAS, BRAF V600E, HER2, and ALK) of lung cancers were not detected. However, tumor recurrence was observed in the mediastinum and esophagus 12 years after surgery. The recurrent tumor had a morphology overlapping with that of the primary tumor; however, it displayed significantly malignant characteristics. The recurrent tumor was not related to high-risk HPV. A high variant allele frequency was observed in tumor suppressor gene BRCA1, TP53, oncogene GNA11, and KIT, which were all missense mutations. Considering the bland features of the primary tumor and the fact of tumor recurrence and undisputed malignant transformation, the basaloid papillary tumor was considered a tumor with uncertain malignant potential.

Peripheral T cell lymphoma initially presenting in lung biopsies: A diagnostic challenge.

BACKGROUND: Primary or secondary pulmonary involvement by peripheral T cell lymphoma (PTCL) is rare and difficult to diagnose particularly via lung biopsies. METHODS: 22 cases of PTCL diagnosed initially in lung biopsies between January 2006 and November 2020 were retrospectively reviewed followed at Nanjing Drum Tower Hospital and the First Affiliated Hospital of Zhengzhou University, respectively, including clinical manifestations, baseline biochemical indexes, images, histological findings and other available ancillary studies such as immunostaining, Epstein-Barr virus encoded RNA (EBER) in situ hybridization and T-cell receptor rearrangement analysis upon diagnosis. RESULTS: The median age of these patients was 59 years old (range: 29-82 years) at diagnosis. The majority of them complained of fever, cough and fatigue. Computed tomography scans mainly revealed multiple ill-defined nodules/masses of various sizes and densities with or without air bronchogram. Microscopically, most lesions showed lymphoid cells with clear cytoplasm and irregular nuclear contours diffusely infiltrating alveolar septa or alveolar spaces in an inflammatory background. Several cases had a predominance of small neoplastic cells (n = 4) with atypical, irregular nuclei. One case showed a diffuse monotonous pattern of growth. Angioinvasion and necrosis were not uncommon findings. The neoplastic cells in all cases were positive for one or more T-cell markers, and negative for B-cell-lineage antigens and EBER. 19 out of 22 patients had complete follow-up information, and 17 patients were dead at the last follow-up. CONCLUSIONS: Pulmonary involvement by PTCL is rare with dismal outcome. Aggressive clinical course and several clinicopathologic clues, albeit unspecific, may alert the pathologists of the possibilities of pulmonary PTCLs.

Recurrent cryptococcal immune reconstitution inflammatory syndrome in an HIV-infected patient after anti-retroviral therapy: a case report.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) in HIV-infected patients presents as a clinical worsening or new presentation of cryptococcal disease as a result of anti-retroviral therapy mediated immune restoration. Recurrent C-IRIS is a rare condition. Recently, recurrent C-IRIS involving the central nervous system, which is thought to require prolonged or alternative immunosuppressive therapy, has been described. Here, we present an unusual case of recurrent C-IRIS, sequentially involving the central nervous system and lymph nodes, in an HIV-infected patient after anti-retroviral therapy. While corticosteroids were used to control the inflammatory cerebral cryptococcomas, lymphadenitis that developed after cessation of corticosteroids resolved without additional immunosuppressive or anti-inflammatory drugs. This case suggests the possibility of site-specific recovery of pathogen-specific immune response after anti-retroviral therapy. In this condition, each episode of C-IRIS may be treated independently, and extended corticosteroids may not always be needed.

Evaluation of a mitochondrial disease criteria scoring system on mitochondrial encephalomyopathy in Chinese patients.

Due to the complicated clinical features of mitochondrial encephalomyopathy, simplified mitochondrial disease criteria (MDC) have recently been established in Europe. This study evaluated the sensitivity and specificity of this scoring system in Chinese patients. Seventy-eight patients with suspected mitochondrial encephalomyopathy were recruited to be scored by the simplified MDC and were further classified into "possible" (2-4), "probable" (5-7), or "definite" categories (≥8). Significant differences were observed between the total scores in the mitochondrial encephalomyopathy group and the other myopathy group. In the mitochondrial encephalomyopathy group, 73.5% of patients had a score above 8, whereas in the other myopathy group, the "definite" percentage was only 3.2%, suggesting the proposed MDC scoring system has a high sensitivity for diagnosis of mitochondrial encephalomyopathy in China. Moreover, there were significant differences in the clinical scores and imaging portions of the MDC, suggesting that the simplified MDC may distinguish mitochondrial disorder from other multisystem disorders to aid in early diagnosis prior to a muscle biopsy.