Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).@*METHODS@#This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.@*RESULTS@#This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.@*CONCLUSIONS@#Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Expert consensus for diagnosis and treatment of thrombocytopenia in China / 中华内科杂志

Thrombocytopenia is the main clinical manifestation or common complication of multiple diseases, but there is still a lack of systematic understanding of pathogenesis, underlying diseases and treatment strategies of thrombocytopenia. Based on evidence-based medicine, this consensus summarizes seven aspects related to thrombocytopenia, including definition, epidemiology, pathogenesis, clinical manifestations, laboratory examination, diagnosis and treatment. This consensus provides an important reference for the diagnosis and treatment of thrombocytopenia.

China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version) / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice.@*METHODS@#The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China.@*RESULTS@#Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation.@*CONCLUSIONS@#A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.

Precise therapy for lung cancer patients with rare sensitive mutations of epidermal growth factor receptor / 中华肿瘤杂志

Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 (Ins), exon 21 (L861), exon 18 (G719X) and exon20 (S768I) mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generations of EGFR-TKIs resistance, some specific types are sensitive to the third generation of EGFR-TKIs. Currently, targeted drugs for Ins20 -Ap32788 mutation has entered into clinical trials. Patients with complex mutations have similar efficacy on EGFR-TKIs in comparison with those with single sensitivity mutations. In conclusion, when patients with rare sensitive mutations received EGFR-TKIs therapy, the efficacy and progression-free survival time is similar to or slightly lower than those with classical sensitive mutations, whereas it is higher than those with wild-type EGFR. Compared with the first generation of EGFR-TKIs, second generation EGFR-TKIs may be more suitable for the treatment of lung cancer patients harboring rare sensitive EGFR mutations.

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis.</p><p><b>METHODS</b>Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk).</p><p><b>RESULTS</b>Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP.</p><p><b>CONCLUSION</b>Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.</p>

Gemifloxacin for the treatment of community-acquired pneumonia and acute exacerbation of chronic bronchitis: a meta-analysis of randomized controlled trials / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gemifloxacin is a fluoroquinolone antibiotic with broad spectrum of antibacterial activity. The aim of the study was to evaluate the comparative effectiveness and safety of gemifloxacin for the treatment of patients with community-acquired pneumonia (CAP) or acute exacerbation of chronic bronchitis (AECB).</p><p><b>METHODS</b>We performed a meta-analysis of randomized controlled trials (RCTs) comparing gemifloxacin with other approved antibiotics. The PubMed, EMBASE, Chinese Biomedical Literature Database and the Cochrane Central Register of Controlled Trials were searched, with no language restrictions.</p><p><b>RESULTS</b>Ten RCTs, comparing gemifloxacin with other quinolones (in 5 RCTs) and β-lactams and/or macrolides (in 5 RCTs), involving 3940 patients, were included in this meta-analysis. Overall, the treatment success was higher for gemifloxacin when compared with other antibiotics (odds ratio 1.39, 95% confidence interval 1.15 - 1.68 in intention-to-treat patients, and 1.33, 1.02 - 1.73 in clinically evaluable patients). There was no significant difference between the compared antibiotics regarding microbiological success (1.19, 0.84 - 1.68) or all-cause mortality (0.82, 0.41 - 1.63). The total drug related adverse events were similar for gemifloxacin when compared with other quinolones (0.89, 0.56 - 1.41), while lower when compared with β-lactams and/or macrolides (0.71, 0.57 - 0.89). In subgroup analyses, administration of gemifloxacin was associated with fewer cases of diarrhoea and more rashes compared with other antibiotics (0.66, 0.48 - 0.91, and 2.36, 1.18 - 4.74, respectively).</p><p><b>CONCLUSIONS</b>The available evidence suggests that gemifloxacin 320 mg oral daily is equivalent or superior to other approved antibiotics in effectiveness and safety for CAP and AECB. The development of rash represents potential limitation of gemifloxacin.</p>

Perfluorocarbon attenuates lipopolysaccharide-mediated inflammatory responses of alveolar epithelial cells in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Toll-like receptor-4 (TLR-4) is integrally involved in lipopolysaccharide (LPS) signaling and has a requisite role in the activation of nuclear factor-κB (NF-κB). The exact mechanisms that lend perfluorocarbon (PFC) liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls (AECs).</p><p><b>METHODS</b>AECs (A549 cells, human lung adenocarcinoma cell line) were divided into four groups: control, PFC, LPS and LPS + PFC (coculture group) groups. Intercellular adhesion molecule-1 (ICAM-1) was detected by ELISA, tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting (proteins of I-κBa and NF-κB p65).</p><p><b>RESULTS</b>ICAM-1, TNF-α and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α and IL-8, the expression of TLR-4 mRNA and the activity of NF-κB.</p><p><b>CONCLUSIONS</b>Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.</p>

Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved.</p><p><b>METHODS</b>MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo.</p><p><b>RESULTS</b>There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-α and IL-1β in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-α, IL-1β and macrophage inflammatory protein (MIP)-1α and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants.</p><p><b>CONCLUSIONS</b>Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses.</p>

Blastomycosis in China: a case report and literature review / 中华医学杂志(英文版)

Blastomycosis is a fungal disease that is endemic in parts of North America. It is very rare in China and also commonly misdiagnosed, often as cancer or other infectious diseases. The clinical profile of a case of disseminated blastomycosis with pulmonary changes and skin ulcers was described. He had been misdiagnosed with tuberculosis, after adequate therapy with a lipid formulation of amphotericin B, followed by itraconazole, the lung and skin lesions improved. Then the five cases reported in China and literatures were reviewed. The aim of this report was to improve the knowledge regarding blastomycosis for physicians in China to avoid delaying adequate therapy.

Endobronchial ultrasound-guided transbronchial needle aspiration of undiagnosed mediastinal lymphadenopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can sample the enlarged mediastinal lymph nodes which are unreachable by conventional bronchoscopy. It is a relatively simple and safe method to see beyond the bronchial tree. We describe and discuss its initial application and our experience.</p><p><b>METHODS</b>From July 2009 to December 2009, 52 patients with undiagnosed enlarged mediastinal lymph nodes were accessed with EBUS-TBNA in the People's Liberation Army General Hospital. Conventional bronchoscopy was performed before EBUS-TBNA, and patients with endobronchial lesions were excluded from this study. Smears fixed in 95% alcohol and histological specimens fixed in formalin were sent to Department of Pathology.</p><p><b>RESULTS</b>EBUS-TBNA was diagnostic in 33 (63%) patients, with diagnosis of lung cancer in 23 patients (14 patients of small cell lung cancer, eight patients with adenocarcinoma, and one patient of squamous carcinoma). Four patients, who had negative EBUS-TBNA results, were later diagnosed with malignancy at thoracotomy. One patient with negative EBUS-TBNA results died of cancer cachexia. The sensitivity, specificity, and positive and negative predictive value of EBUS-TBNA for the diagnosis of neoplastic disease were 85%, 100%, 100%, and 50% respectively. Among the 16 sarcoidosis patients, who were diagnosed by a combination of the clinical and radiological information as well as pathological results obtained by EBUS-TBNA, nine of them had granulomas and benign lymphoid cells detected by EBUS-TBNA. The sensitivity, specificity, and positive and negative predictive value of EBUS-TBNA for the diagnosis of sarcoidosis were 56%, 100%, 100%, and 13%, respectively. Five patients with no definite diagnosis from EBUS-TNBA examination are under close follow-up.</p><p><b>CONCLUSIONS</b>EBUS-TBNA can provide a safe and effective method to sample mediastinal leisions suspected of malignancy. It also adds pathological information needed to make the diagnosis of sarcoidosis.</p>

Gefitinib attenuates murine pulmonary fibrosis induced by bleomycin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated. However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction. This study investigated the effect of gefitinib on lung fibrosis in mice.</p><p><b>METHODS</b>We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib. C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline. Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.</p><p><b>RESULTS</b>The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells. In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens I and III.</p><p><b>CONCLUSIONS</b>These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.</p>

Study on the dynamics of IgG antibody in 311 patients with severe acute respiratory syndrome / 中华流行病学杂志

<p><b>OBJECTIVE</b>To detect the level and dynamic change of severe acute respiratory syndrome (SARS)-coronavirus-specific IgG antibody in conavalescent SARS patients, and to provide information for prevention and vaccine development.</p><p><b>METHODS</b>IgG antibody against coronavirus was detected by ELISA in the blood of 311 convalescent SARS patients for every 2 - 4 weeks. Stata 7.0 statistics software was used to analyse the results.</p><p><b>RESULTS</b>IgG antibody was detected positive on each testing of all the convalescent patients and its peak appeared 35 days after recovery. IgG antibody level showed a 35.8% decrease within one year.</p><p><b>CONCLUSION</b>Data showed that all the SARS convalescent patients had generated high level of specific IgG antibody against coronavirus in the early stage of recovery, but the antibody level declined along with the progress of convalescence, suggesting that the detection of the IgG antibody should go on until it disappeared.</p>

A clinical study of ProGRP as a new tumor marker for small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate the significance of progastrin-releasing peptide (ProGRP) as a new tumor marker for small cell lung cancer (SCLC)..</p><p><b>METHODS</b>Fifty-five patients with pathologically proved SCLC were initially treated and retrospectively studied, in which the level of serum ProGRP was tesed in various situations and its relationship with tumor stage and therapeutic effects was observed.</p><p><b>RESULTS</b>The diagnostic sensitivity and specificity of ProGRP to SCLC were 80.0% and 97.0% respectively. The average ProGRP level in extensive disease of SCLC patients was 820.00 ng/L, significantly higher than 205.86 ng/L in limited disease of SCLC patients (P=0.000 3). In chemotherapy sensitive cases, the ProGRP level had a significant decrease after treatment, while there was no change in failure cases.</p><p><b>CONCLUSIONS</b>ProGRP is a new SCLC tumor marker with high specificity and sensitivity. It has a close relationship with SCLC stage and can be used as a predictor of SCLC to chemotherapy response.</p>

Inhaling beta(2)-agonist with heliox-driven in bronchial asthma / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation.</p><p><b>METHODS</b>Twenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order.</p><p><b>RESULTS</b>The results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)).</p><p><b>CONCLUSIONS</b>Compared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma.</p>

Study on high-rate and low-rate metastatic large-cell lung cancer cell lines via differential display reverse transcript PCR / 中国肺癌杂志

<p><b>BACKGROUND</b>To investigate the differentially expressed gene profile between high-rate and low-rate metastatic large-cell lung cancer cell lines via differential display reverse transcript PCR (DDRT-PCR).</p><p><b>METHODS</b>DDRT-PCR was performed in two large-cell lung cancer cell lines with different metastatic ability. The differentially displayed cDNA were cloned and sequenced and compared with the sequences in the GenBank.</p><p><b>RESULTS</b>Fifty differentially displayed cDNAs were acquired, including 18 function-known genes, 16 function-unknown genes, 16 genomic DNA fragments and 4 ESTs.</p><p><b>CONCLUSIONS</b>The cell lines have different gene expression profiles, and metastasis is affected by multi-gene expression and regulation. Some genes which contribute to the metastasis of lung cancer could be found by DDRT-PCR, and this study gives some new clues to cancer diagnosis and therapy.</p>

ENHANCEMENT OF RESISTANCE OF HUMAN BONE MARROW CELLS TO ANTICANCER AGENTS BY mdrl GENE TRANSFECTION / 解放军医学杂志

To investigate the possibility to enhance resistance of human bone marrow cells to anticancer agents by transfection of mdrl gene. We transferred mdrl gene into human bone marrow cells with plasmid pHaMDR1/A containing human mdrl cDNA by Lipofectin.Pgp,mdrl gene expression product was detected by both flow cytometry and immunohistochemistry.Also,Pgp function was tested by efflux study using rhodamine.The resistance of human bone marrow cells to anticancer agents was assayed by color forming unit culture after exposure to Vincristine,Daunomycin, and Vp16.The results showed that mdrl gene was successfully transferred into human bone marrow cells, and it expressed.Biological activity of Pgp was confirmed by efflux study using rhodamine.Transferred human bone marrow cells possessed resistance to anticancer agents.It suggested that transfection of mdrl gene can increase resistance of human bone marrow cells to anticancer agents.

THE CLINICAL SIGNIFICANCE OF TUMOR MARKERS COMBINATION MEASUREMENT IN DIAGNOSIS OF LUNG CANCER / 解放军医学杂志

To study the clinical significance of combined measurement of neuron specific enolase(NSE), carcinoembryonic antigen(CEA) and Cytokeratin19 fragment 21 1 (CYFRA 21 1 ) in the diagnosis of lung cancer. The serum levels of CEA, NSE, and CYFRA 21 1 in 75 lung cancer patients as well as in 22 benign pulmonary diseases patients were measured by radioimmunoassay. Patients with pulmonary adenocarcinoma had a highest CEA level. Small cell lung carcinoma (SCLC) patients had a highest NSE level, while patients with squamous cell carcinoma of lung had a highest CYFRA 21 1 level. The positive rate of the combination of CEA, NSE, and CYFRA 21 1 for lung cancers was 82 67%. The results suggested that the combined measurement of CEA, NSE, and CYFRA 21 1 was helpful in the diagnosis of lung cancer.