Objective Few reports are seen about the effects of cooling blood and removing stasis on nephrin and podocin . This study was to evaluate the therapy of cooling blood and removing stasis for Henoch -Sch?nlein purpura nephritis ( HSPN) and its ac-tion mechanisms by observing the effects of Danshao Granular Ⅲ on hematuresis , proteinuria and the expressions of nephridial nephrin and podocin in HSPN rats . Methods Twenty-one SD male rats were e-qually randomized to a blank control , an HSPN model , and a Dan-shao group.At 13 weeks after modeling , the animals in the model group were treated intragastrically with distilled water , while those in the Danshao group with Danshao Granular Ⅲtwice daily for 4 weeks. Then, the urinary red blood cell ( RBC) count was examined , the
24 h urinary protein quantity determined , the glomerular mesangial changes observed under the light microscope , the protein expres-sions and distributions of nephrin and podocin detected by indirect immunofluorescence , and their mRNA expressions determined by re-al-time PCR. Results The urinary RBC count and 24 h urine protein quantity were significantly higher in the HSPN model than in the blank control group (26.5/HP vs 0.3/HP and [2.214 ±1.090]g/24 h vs [0.624 ±0.354]g/24 h, both P<0.01).The model rats showed obvious pathological changes in the renal tissue .The urinary RBC count and 24 h urine protein volume were remarkably de-creased in the Danshao group as compared with the models (0.8/HP vs 26.5/HP and [1.000 ±0.651]g/24 h vs [2.214 ±1.090] g/24 h, both P<0.01).The pathological changes in the renal tissue of the Danshao group were reduced in comparison with those of the model group.The protein expression of nephrin was higher in the former than in the latter (65.975 ±14.414 vs 43.520 ±0.632, P<0.01) and so was that of podocin though with no statistically significant difference (P>0.05).The distributions of nephrin and podocin were improved after Danshao treatment .The mRNA expressions of nephrin and podocin were markedly higher in the Danshao group than in the HSPN models (0.530 ±0.089 vs 0.117 ±0.021 and 0.490 ±0.160 vs 0.033 ±0.025, P<0.05). Conclusion Danshao Granular Ⅲ, with its main action mechanisms of cooling blood and removing stasis , can effectively reduce urinary RBC count and urinary protein quantity and improve the symptoms of HSPN in rats .

In this study, laser scanning confocal microscopy (LSCM) was used to determine the location and relative quantity of flavonoids in the leaves of Apocynum venetum L. from the top, middle and basal parts of the branch. The leaves of the plants of one, two and three years old, separately, were collected in July. ANOVA and LSD test were employed in the statistical analysis. The results indicated that flavonoids located mainly in xylem conduit of vein, collenchyma, epidermic cells and cuticle. The data of flavonoids contents under statistical analysis showed that difference existed in the leaves of different parts and different ages. This study provided the reliable scientific material about the analysis of the ecological and the exploitation of the leaves of Apocynum venetom L.

Objective The action mechanisms of Qingfei Oral Liquid ( QFOL) in the treatment of respiratory syncytial virus ( RSV) infection need to be studied more deeply.The aim of this study is to examine the expressions of interleukin ( IL)-10 and IL-17 in the lung tissue and those of Treg and Th17 in the spleen tissue of RSV-infected mice before and after treated with QFOL, and to explore the action mechanisms of QFOL from the perspective of the Treg/Th17 cy-tokines balance. Methods Fifty BABL/c mice were equally ran-domized to five groups: blank control, RSV model, Ribavirin, low-dose QFOL, and high-dose QFOL.Models of RSV ( long strain) infec-tion were made in the latter four groups.At 48 hours after viral activa-tion, the mice of the control and RSV model groups were treated intragastrically with 0.9%normal saline and those in the Ribavirin and QFOL groups with Ribavirin at 0.0025 g/mL and QFOL at 1.33 g/mL and 4 g/mL, respectively, all for 72 hours.Then all the mice were killed and the lung tissue harvested from 5 animals in each group for pathological analysis, while the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid of the other 5 detected by ELISA.The expressions of the cytokines Treg and Th17′in the spleen from 4 mice in each group were determined by flow cytometry. Results Compared with the RSV models, pathologic changes were significantly re-duced in the mice of the QFOL, Ribavirin and control groups (P<0.01), the expression of IL-10 remarkably up-regulated in the low-dose QFOL, high-dose QFOL, Ribavirin, and control groups ([39.21 ±1.57] vs [43.54 ±1.03], [46.64 ±0.48], [47.83 ±0.87], and [50.44 ±1.04] ng/L, all P<0.01), while the level of IL-17 markedly down-regulated ([70.96 ±0.53] vs [55.92 ±0.83], [33.66 ±0.70], [21.92 ±1.38], and [9.42 ±0.59] pg/mL, all P<0.01).The expressions of Treg/Th17′were significantly in-creased in the low-dose QFOL, high-dose QFOL, Ribavirin, and control groups (2.89 ±0.52, 6.38 ±0.36, 3.95 ±0.26, and 3.54 ± 0.85) as compared with that in the RSV models (0.96 ±0.16) (all P<0.01).Both low-and high-dose QFOL groups showed statisti-cally significant differences from the Ribavirin group in the levels of Treg, Th17, and Treg/Th17 (P<0.05). Conclusion QFOL can regulate the balance of Treg/Th17, increase the expression of IL-10 and decrease that of IL-17 in the lung tissue of RSV-infected mice, which further proves the efficacy of QFOL in the treatment of RSV-induced pneumonia.

OBJECTIVETo explore the clinicopathological characteristics and imaging features of lung adenocarcinoma with a micropapillary pattern (MPP).

METHODSEighty cases of pulmonary adenocarcinoma with a micropapillary pattern treated in our hospital from July 2011 to December 2012 were selected to retrospectively analyze their clinicopathological characteristics and imaging features.

RESULTSAmong the 80 cases of lung adenocarcinoma with MPP, there were 38 cases of stage I (47.5%), 12 cases of stage II (15.0%), 25 cases of stage III (31.3%) and 5 cases of stage IV (6.2%). There were 14 cases of moderately differentiated (17.5%) and moderately/poorly differentiated (82.5%) tumors. Sixty-three cases had pleural involvement, vascular invasion, involving the bronchial wall, invasion of large vessels, nerve invasion, and lymph node metastasis (at least one of them) (78.8%). Immunohistochemical staining revealed that both positive rates of TTF-1 and CK7 were 100%, and that of pulmonary surfactant apolipoprotein-A (SPA) was 84.0%. Imaging examination revealed hilar or mediastinal lymph node enlargement in 15 cases (18.8%). but the pathology confirmed hilar or mediastinal lymph node metastasis in 36 cases (45.0%). Lung CT imaging showed that the majority of the cases were peripheral type, and only a few of central type, and most cases were solid lesions, with lobulation, spiculation, pleural indentation, and vascular convergence sign, while there were few ground-glass opacity sign and vacuole sign.

CONCLUSIONSLung adenocarcinoma with MPP component often presents with early invasions of pleura, blood vessels, lymphatic vessels, and lymph nodes. Imaging manifestation of this cancer mainly shows as peripheral and solid lesions, often with lobulation, spiculation, pleural indentation, vascular convergence sign, but GGO and vacuole signs are unusual. Overexpression of TTF-1, CK7 and SPA, and elevated CEA level are associated with clinical staging of the disease.

Adenocarcinoma ; diagnostic imaging ; metabolism ; pathology ; Adenocarcinoma, Papillary ; diagnostic imaging ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Apolipoproteins A ; metabolism ; Carcinoembryonic Antigen ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Keratin-7 ; metabolism ; Lung Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies ; Tomography, X-Ray Computed ; Transcription Factors

Lung cancer is the most common malignancy and is a major public health problem worldwide. Programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors provide a new treatment strategy for non-small cell lung cancer (NSCLC). The existing biomarkers all have advantages and defects in selecting patients who benefit from immunotherapy. The multiplex immunohistochemistry/immunofluorescence (mIHC/IF) provides multiplex staining, allows comprehensive studies of cellular composition, cellular functions and cell-cell interactions. A number of studies have used mIHC/IF to explore specific immune cells in tumor immune microenvironment (TIME) and found that it is helpful for clinical prognosis and efficacy prediction in patients with lung cancer. In the era of immunotherapy for lung cancer, this technique has a bright future in translational research and clinical practice. The research progress of mIHC/IF detection in lung cancer immunotherapy is summarized in this review.
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A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.
Female ; Humans ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Crizotinib/therapeutic use* ; Lung Neoplasms/drug therapy* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Lung Diseases, Interstitial/diagnosis*

Objective:To explore the clinical significance of multi-sample next-generation sequencing (NGS) in detecting gene mutations in non-small cell lung cancer (NSCLC), so as to provide a basis for individualized targeted treatment.Methods:The data of 51 patients with NSCLC in the First Affiliated Hospital of Zhejiang University Medical College from June 2016 to February 2019 was retrospectively analyzed. The patients' age, gender, smoking status, pathological type, tumor staging, pleural invasion status and meningeal invasion status were collected, and the tissues, cerebrospinal fluid, pleural effusion and plasma samples were detected by NGS. The correlations between the driver gene mutations [epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)] and the clinicopathological features of patients were analyzed by χ 2 test or Fisher exact probability method. Cohen Kappa coefficient analysis was used to compare the consistency of NGS detection results in different samples. Results:Among the 51 patients, 3 different types of specimens were examined in 7 patients. Of which, the driver gene mutations were all positive in 3 cerebrospinal fluid samples and double gene mutations were found in 2 hydrothorax samples. Driver gene mutations were more common in female [90.48% (19/21) vs. 50.00% (15/30), χ 2 = 9.107, P = 0.003], non-smokers [80.00% (24/30) vs. 47.62 (10/21), χ 2 = 5.829, P = 0.016], adenocarcinoma patients [72.34% (34/47) vs. 0, P = 0.017] and patients with malignant pleural effusion [92.86% (13/14) vs. 56.76% (21/37), χ 2 = 4.443, P = 0.035], and the differences were statistically significant. However, there was no statistically significant difference in mutations of driver gene among patients with different age or tumor stages (both P > 0.05). The consistency rate of genetic test results of the driver gene mutations in 37 plasma samples and matched tissue samples was 70.27% (26/37), κ value was 0.430, which suggested a good consistency between them. Conclusions:In patients with advanced NSCLC, gene detection of cerebrospinal fluid is of high application value for patients with meningeal metastasis; for patients with pleural invasion, gene detection of pleural effusion is an effective means to screen targeted therapy drugs. NGS detection of multiple specimens can better reflect the status of gene mutations and guide the individualized targeted therapy of lung cancer patients.

BACKGROUND: Advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma had a high overall incidence of brain metastasis during the full course, and local brain radiotherapy combined with systemic targeted therapy may be a better strategy. This study aimed to identify the prognostic factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients who received EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in combination with gamma knife radiosurgery. METHODS: Retrospective analysis of EGFR-mutant lung adenocarcinoma patients with brain metastases which developed at initial diagnosis or during EGFR-TKIs treatment period were performed. Intracranial progression free survival (PFS) was statistically analyzed between different subgroups to find out the prognostic factors including gender, age, smoking history, extracranial metastasis, EGFR mutation type, size and number of intracranial lesions, carcino-embryonic antigen (CEA) level, lung-molGPA score and so on. RESULTS: A total of 74 EGFR-mutant brain-metastatic lung adenocarcinoma patients were enrolled in this study, with median intracranial PFS of 14.7 months. One-year intracranial-progression-free rate was 58.5%, and two-year rate was 22.2%. Univariate survival analysis showed that patients with lower CEA level at initial diagnosis (<10 ng/L)(16.9 months vs 12.6 months, P=0.012) and smaller intracranial lesions (<2 cm)(15.4 months vs 10.8 months, P=0.021) and higher lung-molGPA score (>3)(15 months vs 12.6 months, P=0.041) were prone to have a superior intracranial PFS. Multivariate analysis showed that CEA≥10 ng/mL and intracranial lesion≥2 cm were the independent risk factors of intracranial PFS. CONCLUSIONS EGFR-TKIs in combination with gamma knife radiosurgery was an efficient treatment option to control the cranial tumor lesion. CEA≥10 μg/L at initial diagnosis and intracranial lesion≥2 cm were the risk factors of EGFR-mutant brain-metastatic lung adenocarcinoma patients receiving EGFR-TKIs in combination with gamma knife radiosurgery.
Adenocarcinoma of Lung ; drug therapy ; pathology ; radiotherapy ; therapy ; Adult ; Aged ; Brain Neoplasms ; secondary ; Combined Modality Therapy ; ErbB Receptors ; antagonists & inhibitors ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Radiosurgery ; Retrospective Studies

PD-1/PD-L1 inhibitors play an important role in the first-line and second-line treatment of non-small cell lung cancer (NSCLC), indicating a new treatment strategy of NSCLC. Completed clinical trials have shown that effective detection of PD-L1 expression is the key to the use of immunosuppressive agents. However, the gold standard for PD-L1 detection has still lacked. In recent years, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) have been continuously innovated, which accounts for good prospect in PD-L1 detection. The research progress of PD-L1 detection methods in NSCLC is summarized in this review.
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B7-H1 Antigen ; analysis ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; metabolism ; Enzyme-Linked Immunosorbent Assay ; methods ; Humans ; Immunohistochemistry ; methods ; Lung Neoplasms ; diagnosis ; metabolism ; Reproducibility of Results ; Sensitivity and Specificity

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Receptor, ErbB-2/genetics* ; Mutation ; Antineoplastic Agents/pharmacology* ; Signal Transduction ; Protein Kinase Inhibitors/therapeutic use*