[Analysis of clinical characteristics of 43 patients with pulmonary mycosis diagnosed by pathology].

OBJECTIVE: To observe the etiological distribution, clinical presentations and imaging features of pulmonary mycosis that is diagnosed by pathology. METHODS: The etiological distribution, clinical presentations and imaging features of patients with pulmonary mycosis, who were collected in the Affiliated Hospital of Jining Medical University from January 2018 to July 2020, were retrospectively analyzed. The diagnosis of all the patients were confirmed by pathological examination, of lung or bronchi tissue that were obtained through operation, bronchoscope or percutaneous lung puncture biopsy. RESULTS: There were 26 patients' (60.47%, 26/43) pathological specimens were obtained by operation, 14 cases (32.56%, 14/43) were obtained by bronchoscope, and 3 cases (6.98%, 3/43) were obtained by percutaneous lung puncture biopsy. Of the 43 patients who were diagnosed pulmonary mycosis by pathology, 27 patients (62.79%, 27/43) suffered from pulmonary aspergillosis, 11 patients (25.58%, 11/43) suffered from pulmonary cryptococcosis, 3 patients (6.98%, 3/43) suffered from pulmonary mucormycosis, and 2 patients (4.65%, 2/43) suffered from pulmonary candidiasis. There were 27 patients (62.79%, 27/43) with pulmonary fungal disease complicating risk factors of fungal infection, including diabetes mellitus (23.26%,10/43), malignant tumor (16.28%, 7/43), bronchiectasis (9.30%, 4/43), hepatitis B virus (HBV) carrier (6.98%, 3/43), taking glucocorticoids (4.65%, 2/43), pulmonary tuberculosis (4.65%, 2/43), and chemotherapy following colon carcinoma operation (2.33%, 1/43). The common clinical presentations included cough (55.81%, 24/43), expectoration (48.84%, 21/43), hemoptysis (37.21%, 16/43), fever (20.93%, 9/43), gasping (18.60%, 8/43), chest pain (16.28%, 7/43), and hoarseness (3.13%, 1/43). Imaging features of chest included lung nodes in 20 cases (46.51%, 20/43), vascular welt sign in 12 cases (27.91%, 12/43), exudative process in 10 cases (23.26%, 10/43), lung mass or consolidation in 8 cases (18.60%, 8/43), cavitary lesions in 7 cases (16.28%, 7/43), thicken bronchus wall and narrow lumina in 6 cases (13.95%, 6/43), air crescent in 5 cases (11.63%, 5/43). CONCLUSIONS: The pulmonary aspergillosis and cryptococcosis are mainly in pulmonary mycosis diagnosed by pathology. The common complications are diabetes mellitus and malignant tumor. The common clinical presentations are cough, expectoration, and hemoptysis. The main imaging features of chest are lung nodes and vascular welt sign can be found in most of pulmonary cryptococcosis.

Risk factors for illness severity in patients with COVID-19 pneumonia: a prospective cohort study.

Background: Although COVID-19 pneumonia is spreading internationally, knowledge regarding the factors associated with the illness severity of patients remains limited. We aimed to identify the factors associated with the disease severity of patients with COVID-19 pneumonia induced by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We prospectively enrolled a single-center case series of adult patients with COVID-19 admitted to the Infectious Disease Hospital of Jining, Jining City, Shandong Province, China, from January 24 to March 1, 2020. Demographics, clinical characteristics, and laboratory findings were compared to investigate the risk factors related with the disease severity of COVID-19 pneumonia patients. Results: We included a total of 78 patients with COVID-19 pneumonia, of whom 6 had the severe type. As compared to a moderately ill cohort, our analysis showed that shortness of breath, fatigue, longer days from illness onset to diagnosis confirmed, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, lymphocyte counts < 1.0 × 109/L, platelet < 100 × 109/L, C-reactive protein (CRP) > 10 mg/L, neutrophil to platelet ratio (NPR) > 2.3, neutrophil to lymphocyte ratio (NLR) > 3.9, aspartate aminotransferase (AST) > 40 U/L, albumin < 40 g/L, lactate dehydrogenase (LDH) > 245 U/L, and glucose > 6.1 mmol/L were predictors of disease severity in COVID-19 pneumonia. In the sex-, age-, and comorbid illness-matched case-control study, neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L remained associated with the early detection and identification of severe patients. Conclusion: We demonstrated that neutrophil percentages > 70%, neutrophil counts > 6.3 × 109/L, lymphocyte percentages < 20%, NPR > 2.3, NLR > 3.9, albumin < 40 g/L, and LDH > 245 U/L might predict the severity of illness in patients with COVID-19 pneumonia.

Clinical Characteristics of Infections Caused by Streptococcus Anginosus Group.

This study aimed to investigate the clinical characteristics, distribution of different strains and risk factors of patients infected with Streptococcus anginosus group (SAG). In the population of 463 patients, the male-to-female ratio was 1.95:1, and the patient age ranged from 6 months to 103 years. There were 49 children (10.58%), 311 young and middle-aged adults (67.17%), and 103 elderly adults (22.25%). Approximately 45.4% had underlying conditions, which were mostly malignant tumors and diabetes. Of the 463 specimens, 254 were S. anginosus (54.86%), 173 were S. constellatus (37.37%), and 36 were S. intermedius (7.77%). According to the age distribution, the incidence peaked in the 35-54 year age group. Different sites of infection had statistically significant differences regarding the constituent ratios of these three species. Different age groups also exhibited statistically significant differences in constituent ratios of the pathogenic organisms, as well as organ infections. In our population, 269 were clinically cured, 184 reported satisfactory improvement, and 10 died. SAG, as an opportunistic pathogen, can induce pyogenic infections in patients of all ages and shows no significant gender predilection in any age group. The three pathogenic organisms had differences with respect to patient age and infections of body sites.

SPINK1 is a prognosis predicting factor of non-small cell lung cancer and regulates redox homeostasis.

Serine protease inhibitor Kazal-type 1 (SPINK1) is a trypsin kinase inhibitor, which is involved in the development of inflammation, cell proliferation and cancer development and progression. However, the prognostic value of SPINK1 in non-small cell lung cancer (NSCLC) and its ability to regulate intrinsic redox homeostasis have, to the best of our knowledge, not been previously investigated. In the present study, it was revealed that SPINK1 is highly expressed in NSCLC tissue samples compared with normal tissue samples, and may be a potential prognostic marker of NSCLC. Functional analyses demonstrated that SPINK1 promoted tumor cell growth and inhibited apoptosis through maintaining redox homeostasis by regulating the nuclear factor erythroid 2-related factor 2 pathways. It has been proposed that SPINK1 could be a prognostic marker of NSCLC and a novel antioxidant promoter under oxidative stress conditions in NSCLC.

[Diagnostic value of the combinations of bronchoalveolar lavage fluid galactomannan test and serum galactomannan test in invasive pulmonary aspergillosis].

OBJECTIVE: To evaluate the accuracy and diagnostic value of bronchoalveolar lavage fluid galactomannan test (BALF-GM) combined with serum GM test on invasive pulmonary aspergillosis (IPA). METHODS: 190 cases of BALF-GM and 4 787 cases of serum GM specimens suspected of fungal infection in patients admitted to Affiliated Hospital of Jining Medical University from January 2016 to June 2018 were enrolled and analyzed. All patients were classified into clinically confirmed IPA, clinically diagnosed IPA, suspected IPA and excluded IPA according to the classification standard of Expert consensus on diagnosis and treatment of pulmonary mycosis. The coincidence rate of BALF and serum GM test results with clinical diagnosis was analyzed. Receiver operating characteristic (ROC) curve was performed, and the diagnostic value of BALF and serum GM test alone or in combination for IPA was evaluated. Subgroup analysis was performed in patients with normal or abnormal immune function, and the sensitivity and specificity of BALF and serum GM test were compared separately or jointly. RESULTS: The positive rate of BALF-GM was 46.8% (89/190), and 10.4% (497/4 787) on serum GM. Among them, 156 patients were both tested on BALF and serum GM. There were 44 cases with both positive in BALF and serum GM, the coincidence rate of clinical definite was 93.2% (41/44). There were 34 cases with positive BALF-GM and negative GM test in serum, and the coincidence rate of clinical definite was 64.7% (22/34). There were 56 cases positive in serum GM and negative in BALF-GM, and the coincidence rate of clinical definite was 48.2% (27/56). BALF and serum GM tests were both negative in 22 cases, and the coincidence rate of exclusion diagnosis was 90.9% (20/22). ROC curve analysis showed that the diagnostic value of BALF-GM test combined with serum GM test for IPA was better than that of BALF-GM test or serum GM test alone [area under ROC curve (AUC): 0.992 vs. 0.983, 0.976]. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.3%, 87.0%, 93.2% and 90.9%, respectively. Subgroup analysis showed that among 89 patients with positive BALF-GM test, 85 cases (95.5%) had normal immune function and 4 cases (4.5%) had unknown condition. Among 497 patients with positive serum GM test, 12 cases (2.4%) had normal immune function, 372 cases (74.9%) had abnormal immune function and 113 cases (22.7%) were uncertain. It was shown by ROC curve analysis that the sensitivity of positive BALF-GM test in diagnosis of IPA in patients with normal immune function was higher than that of positive serum GM test (95.6% vs. 88.9%), while the sensitivity of positive serum GM test in patients with abnormal immune function was higher than that of positive BALF-GM test (91.8% vs. 89.9%). CONCLUSIONS: The results of BALF and serum GM tests are in good agreement with clinical diagnosis, and the combined detection of BALF and serum GM is more valuable for IPA diagnosis than single detection, especially for patients with unknown immune function.

MiR-24 promotes migration and invasion of non-small cell lung cancer by targeting ZNF367.

PURPOSE: Non-small lung cancer (NSCLC) is one of most common cancers worldwide. microRNAs (miRNAs) play an important role in animal biological processes, such as cell growth, differentiation and apoptosis. The aim of this study was to investigate whether MiR-24 can regulate cell proliferation of NSCLC by targeting ZNF367. METHODS: Real time quantitative PCR (qRT-PCR) was used to detect the expression levels of MiR-24 and ZNF367. Western blot assay was employed to analyze the protein levels. Luciferase reporter assay was used to test the target gene of MiR-24. MTT assay was used to detect cell proliferation. RESULTS: MiR-24 was significantly up-regulated in NSCLC tissues compared with their corresponding nontumorous tissues (p<0.05). Over-expression of MiR-24 could significantly promoted cell migration and invasion (p<0.05). ZNF367 was a downstream target of MiR-24 and down-regulated by MiR-24. Knockdown of ZNF367 remarkably promoted NSCLC cell proliferation (p<0.05). CONCLUSIONS: The novel identified MiR-24/ZNF367 axis offers new insights into tumorigenesis of NSCLC and a new biomarker for NSCLC treatment.

Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD.

Purpose: This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients. Methods: A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study. The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay. The correlations between their expression levels and clinical factors of patients were determined using linear regression methods. Results: The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history (P<0.05), but negatively correlated with the pulmonary function (P<0.05) of patients. The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history (P<0.05), but positively correlated with the pulmonary function (P<0.05) of patients. Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35. Conclusion: The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD.

Two cases of endobronchial aspergilloma with lung cancer: a review the literature of endobronchial aspergilloma with underlying malignant lesions of the lung.

Endobronchial aspergilloma is a rare disease entity with pulmonary involvement of aspergillus. Few cases of endobronchial aspergilloma associated with malignant lesions have been reported in the literature. We present 2 more cases of endobronchial aspergilloma with underlying lung cancer. And summarize the published literatures to investigate the clinical manifestations, bronchoscopic characters, imaging performances in patients with endobronchial aspergilloma with underlying malignant lesions of the lung. A review of the literature reveals 8 cases of endobronchial aspergilloma with coexisting lung malignant lesions upon presentation. The medical details of the patients including age, sex, clinical symptoms, radiological manifestations bronchoscopic characters, diagnosis and treatment are summarized. Endobronchial aspergilloma is usually incidentally detected in patients with underlying lung disease. With the increasing popularity of flexible bronchoscopy, it is being recognized as a necrotic mass causing bronchial obstruction. We should be paid more attention to prevent misdiagnosis of combined endobronchial aspergilloma and lung malignant diseases.

Motor and behavioral phenotype in conditional mutants with targeted ablation of cortical D1 dopamine receptor-expressing cells.

D1-dopamine receptors (Drd1a) are highly expressed in the deep layers of the cerebral cortex and the striatum. A number of human diseases such as Huntington disease and schizophrenia are known to have cortical pathology involving dopamine receptor expressing neurons. To illuminate their functional role, we exploited a Cre/Lox molecular paradigm to generate Emx-1(tox) MUT mice, a transgenic line in which cortical Drd1a-expressing pyramidal neurons were selectively ablated. Emx-1(tox) MUT mice displayed prominent forelimb dystonia, hyperkinesia, ataxia on rotarod testing, heightened anxiety-like behavior, and age-dependent abnormalities in a test of social interaction. The latter occurred in the context of normal working memory on testing in the Y-maze and for novel object recognition. Some motor and behavioral abnormalities in Emx-1(tox) MUT mice overlapped with those in CamKIIα(tox) MUT transgenic mice, a line in which both striatal and cortical Drd1a-expressing cells were ablated. Although Emx-1(tox) MUT mice had normal striatal anatomy, both Emx-1(tox) MUT and CamKIIα(tox) MUT mice displayed selective neuronal loss in cortical layers V and VI. This study shows that loss of cortical Drd1a-expressing cells is sufficient to produce deficits in multiple motor and behavioral domains, independent of striatal mechanisms. Primary cortical changes in the D1 dopamine receptor compartment are therefore likely to model a number of core clinical features in disorders such as Huntington disease and schizophrenia.

Resolving pathobiological mechanisms relating to Huntington disease: gait, balance, and involuntary movements in mice with targeted ablation of striatal D1 dopamine receptor cells.

Progressive cell loss is observed in the striatum, cerebral cortex, thalamus, hypothalamus, subthalamic nucleus and hippocampus in Huntington disease. In the striatum, dopamine-responsive medium spiny neurons are preferentially lost. Clinical features include involuntary movements, gait and orofacial impairments in addition to cognitive deficits and psychosis, anxiety and mood disorders. We utilized the Cre-LoxP system to generate mutant mice with selective postnatal ablation of D1 dopamine receptor-expressing striatal neurons to determine which elements of the complex Huntington disease phenotype relate to loss of this neuronal subpopulation. Mutant mice had reduced body weight, locomotor slowing, reduced rearing, ataxia, a short stride length wide-based erratic gait, impairment in orofacial movements and displayed haloperidol-suppressible tic-like movements. The mutation was associated with an anxiolytic profile. Mutant mice had significant striatal-specific atrophy and astrogliosis. D1-expressing cell number was reduced throughout the rostrocaudal extent of the dorsal striatum consistent with partial destruction of the striatonigral pathway. Additional striatal changes included up-regulated D2 and enkephalin mRNA, and an increased density of D2 and preproenkephalin-expressing projection neurons, and striatal neuropeptide Y and cholinergic interneurons. These data suggest that striatal D1-cell-ablation alone may account for the involuntary movements and locomotor, balance and orofacial deficits seen not only in HD but also in HD phenocopy syndromes with striatal atrophy. Therapeutic strategies would therefore need to target striatal D1 cells to ameliorate deficits especially when the clinical presentation is dominated by a bradykinetic/ataxic phenotype with involuntary movements.

Behavioural and anatomical characterization of mutant mice with targeted deletion of D1 dopamine receptor-expressing cells: response to acute morphine.

Considerable topographic overlap exists between brain opioidergic and dopaminergic neurons. Pharmacological blockade of the dopamine D(1) receptor (Drd1a) reverses several behavioural phenomena elicited by opioids. The present study examines the effects of morphine in adult mutant (MUT) mice expressing the attenuated diphtheria toxin-176 gene in Drd1a-expressing cells, a mutant line shown previously to undergo post-natal striatal atrophy and loss of Drd1a-expression. MUT and wild-type mice were assessed behaviourally following acute administration of 10 mg/kg morphine. Treatment with morphine reduced locomotion and rearing similarly in both genotypes but reduced total grooming only in MUT mice. Morphine-induced Straub tail and stillness were heightened in MUT mice. Chewing and sifting were decreased in MUT mice and these effects were not modified by morphine. Loss of striatal Drd1-positive cells and up-regulated D(2)-expression, as reflected in down-regulated D(1)-like and up-regulated D(2)-like binding, respectively, is not uniform along the cranio-caudal extent in this model but appears to be greater in the caudal striatum. Preferential caudal loss of µ-opioid-expression, a marker for the striosomal compartment, was seen. These data indicate that Drd1a-positive cell loss modifies the exploratory behavioural response elicited by morphine, unmasking novel morphine-induced MUT-specific behaviours and generating a hypersensitivity to morphine for others.

Age-related behavioural phenotype and cellular characterisation of mice with progressive ablation of D1 dopamine receptor-expressing cells.

In this study we characterize the behavioural and cellular phenotype of mutant (MUT) mice with progressive loss of D1 dopamine receptor (Drd1a)-expressing cells. Adult [14-19 weeks] MUT mice showed intact working memory in the spontaneous alternation test but evidenced anxiety-like behaviour in the elevated plus maze and the light-dark test. The ethogram of mature adult MUT [average age 22 weeks] was compared with that of young adult MUT mice [average age 12 weeks]. While MUT mice evidenced hyperactivity over initial exploration at both time points, the topography of hyperactivity shifted. Moreover, initial hyperactivity was sustained over habituation at 12 weeks, but not at 22 weeks. Thus, by 22 weeks MUT mice evidenced shifts in, and mitigation of, these early phenotypic effects. However, orofacial behaviours of chewing and sifting were reduced similarly at 12 and 22 weeks. These data support the hypothesis that aspects of the mutant phenotype change with time. Quantitative autoradiography at 20 weeks revealed loss of D1-like dopamine receptor binding in the entire basal ganglia, with upregulated D2-like binding. There appear to be topographically specific interactions between normal maturational processes and compensatory mechanisms evoked subsequent to targeted ablation of D1 dopamine receptor-expressing cells. Understanding the mechanistic bases of mitigation vs persistence of individual phenotypes in relation to neural adaptation consequent to cell loss may lead to novel therapeutic strategies for basal ganglia disorders.

Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior.

Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate an animal model in which D1 dopamine receptor (Drd1a)+ cells are progressively ablated in the postnatal brain. Striatal Drd1a, substance P, and dynorphin expression is progressively lost, whereas D2 dopamine receptor (Drd2) and enkephalin expression is up-regulated. Magnetic resonance spectroscopic analysis demonstrated early elevation of the striatal choline/creatine ratio, a finding associated with extensive reactive striatal astrogliosis. Sequential MRI demonstrated a progressive reduction in striatal volume and secondary ventricular enlargement confirmed to be due to loss of striatal cells. Mutant mice had normal gait and rotarod performance but displayed hindlimb dystonia, locomotor hyperactivity, and handling-induced electrographically verified spontaneous seizures. Ethological assessment identified an increase in rearing and impairments in the oral behaviors of sifting and chewing. In line with the limbic seizure profile, cell loss, astrogliosis, microgliosis, and down-regulated dynorphin expression were seen in the hippocampal dentate gyrus. This study specifically implicates Drd1a+ cell loss with tail suspension hindlimb dystonia, hyperactivity, and abnormal oral function. The latter may relate to the speech and swallowing disturbances and the classic sign of tongue-protrusion motor impersistence observed in Huntington's disease. In addition, the findings of this study support the notion that Drd1a and Drd2 are segregated on striatal projection neurons.