[Investigation on status of lung cancer cough management and concept and practice of lung cancer cough management in Chinese medical providers].

Objective: Investigate the current situation of lung cancer cough diagnosis and treatment and the awareness of related issues among Chinese medical providers. Methods: Doctors, nurses, pharmacists from the oncology department, respiratory department, or general department were investigated using an electronic questionnaire from January 29 to March 29, 2021. There were 25 questions about lung cancer in the questionnaire. The questionnaire was including the most common accompanying symptoms in patients with lung cancer, the incidence of lung cancer-related cough, the assessment of the proportion of central antitussive drugs, and the commonly used central antitussives. Results: Questionnaires from 2 424 medical providers were collected from 402 hospitals in 21 provincial administrative units. Cough was the most common symptom in lung cancer. Most physicians believed that the incidence of lung cancer-related cough was 51%~75%, while the proportion of patients satisfied with the treatment was only 11%~20%. The evaluation of lung cancer-related cough was seriously insufficient. The leading cause of lung cancer-related cough was tumors. And the main problem was the inadequate antitussive effect of drugs in lung cancer-related cough management. The proportion of central antitussive medication usage in the secondary and tertiary hospitals was 93.9% and 92.0%, significantly higher than 75.0% in Primary hospitals (χ²=8.390, P=0.015). The proportion of the physicians who underhanded that codeine is at risk of addiction was 76.6% and 72.0% in the secondary and tertiary hospitals, which were significantly higher than 53.9% in Primary hospitals (χ²=9.240, P=0.010). In different occupations, the proportions of doctors and pharmacists who knew the risk of addicting to codeine were 73.0% and 82.6%, which were significantly higher than the 66.4% of nurses (χ²=21.200, P<0.001). The Chinese medical providers were lack of training about the basic knowledge of using central antitussive medication. Conclusions: The proportion of patients who were satisfied with the effect of cough treatment is low. The medical staff did not have enough awareness of this. There was an urgent need to develop a consensus and standardize lung cancer cough diagnosis and treatment in China.

[Diagnosis and treatment of Chlamydia psittaci pneumonia: experiences of 8 cases].

Objective: In order to improve the understanding and clinical treatment of Chlamydia psittaci pneumonia, we analyzed the clinical manifestations, laboratory test results and imaging features of 8 patients. Methods: We collected the clinical data of 8 patients with Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation-sequencing (mNGS) from November 2018 to February 2020, including clinical features, chest CT scan, pathological features and antibiotic use. Results: A total of one male and 7 females, aged from 45 to 85 years(median 62 years), were included in this study. All the patients had high fever, cough and most had expectoration (6/8). The leukocyte count and PCT level were mostly normal (7/8). However, we observed decreased lymphocyte count(5/8), elevated C-reactive protein in all patients, and increased ESR in most patients (7/8). The chest CT of all the patients showed large patchy consolidation, with one case having pleural effusion. The pathological manifestations were nonspecific, showing infiltration of inflammatory cells and exudation. Moxifloxacin and/or doxycycline were administered after diagnosis, and the course of treatment lasted from 14 to 21 days.Chest CT showed absorption of lesions following treatment Conclusions: Chlamydia psittaci pneumonia showed certain characteristics, including high fever with pulmonary patchy consolidation, and normal white blood cell count. Molecular diagnostic methods such as mNGS could lead to rapid diagnosis and treatment which can shorten the course of hospitalization and thus improve prognosis.

[Effect of VDR gene silencing on proliferation and NF-κB activation of airway smooth muscle cells].

Objective: To investigate the effect of VDR gene silencing on proliferation of airway smooth muscle cells (ASMCs) and elucidate the role of NF-κB. Methods: A recombinant lentiviral vector specifically targeting VDR gene in rat was constructed by RNA interference. Rat ASMCs were divided into blank group, empty vector group and interference group. ASM cell line model stably silencing the VDR gene RNA expressing was selected by puromycin. Then MTT colorimetric assay and cell cycle analysis by flow cytometry were used to examine cell proliferation. The activation of nuclear factor-κB was determined by immunofluorescence double label method. Moreover, NF-κB-dependent transcription activity was tested through luciferase reporter gene assay. Western blotting was used for IκBα and phospho-IκBα protein levels and actinomycin D treatment was used to determine IκBα mRNA stability. All statistical analyses were performed using SPSS version 23.0 software. Differences between groups were analyzed using one-way ANOVA analysis. Multiple comparisons among groups were made by Student-Newman-Keuls test. Results: (1) As compared with those in the blank group and the empty vector group, the cell proliferation index (PI) and the percent of ASMCs at G2/M phase in the interference group were markedly increased (P<0.05), but their percent at G0/1 phase was decreased (P<0.05).(2) In the interference group, the nuclear translocation of NF-κB p65 in ASMCs was obviously induced. And its level of receptor gene NF-κB p65 (1.37±0.28) was significantly higher than that in the blank group (1.00±0.19,P=0.031) and in the empty vector group (0.96±0.18,P=0.027).(3) In the interference group, the IκBα protein level in ASMCs (0.13±0.04) was obviously less than that in the blank group (0.29±0.05, P=0.023) and in the empty vector group (0.32±0.07, P=0.014). Oppositely, the p-IκBα/IκBα level in the interference group (0.86±0.04) was much more than that in the blank control group (0.41±0.07, P=0.026) and in the empty vector group (0.37±0.05, P=0.017). (4) In the interference group, IκBα mRNA showed a shorter half-life, (171.31±9.67) min, compared to that in the blank group [(224.69±7.95) min,P=0.032] and in the empty vector group [(230.41±6.37) min,P=0.035]. Conclusion: VDR gene silencing could promote ASMC proliferation and the underlying mechanism may involve the activation of NF-κB signaling pathway.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

[Pulmonary extranodal natural killer/T-cell lymphoma: clinical analysis of three cases].

Objective: To improve the understanding of pulmonary involvement of extranodal natural killer/T-cell lymphoma (ENKTL) by analyzing the clinical manifestations, imaging and pathological features of this disease. Methods: Three cases of ENKTL, proven by pathological diagnosis in Fuzhou General Clinical Medical College of Fujian Medical University, were retrospectively analyzed. Results: All of the 3 cases were males, aged 74, 61 and 49 years, respectively. The main clinical symptoms included cold and fever. One patient had nasal congestion and runny nose. Chest CT showed multiple lung nodules (n=3), masses (n=2) and patchy shadows (n=2), with irregular lesions and clear boundaries. The 3 cases had been misdiagnosed as community acquired pneumonia, and treated with intravenous injection of moxifloxacin. ENKTL was confirmed by CT-guided percutaneous biopsy with immunohistochemical staining, which showed that 3 cases were positive for CD(56), CD(2), in situ hybridization for EBV encoded RNA (EBER), while negative for CD(20), and 2 cases were positive for CD(3), Granzyme B; and 1 case was positive for T-cell intracytoplasmic antigen-1. All 3 patients received chemotherapy, but 2 patients died, one of rejection 1 month later after bone marrow transplantation. One patient had improved after chemotherapy with follow-up. Conclusion: ENKTL should be considered when patients presented with fever, multiple lung nodules or consolidations which were non-responsive to antibiotics. Lung biopsy was the key to diagnosis.

[Epidemiological investigation and analysis of an outbreak of mycoplasma pneumoniae pneumonia in adult].

Objective: To conduct an epidemiological investigation and analysis of an outbreak of mycoplasma pneumonia in adults. Methods: The first case was a 23-year-old male came from the Third Military Medical University, who served as an intern in the Fuzhou General Hospital of PLA and presented on July 16, 2015 with a history of low-grade fever, dizziness, fatigue and chest tightness. Chest CT revealed pulmonary nodules shadow. It was found that other 11 individuals who had been in close contact with the first patient also had similar pulmonary nodules shadow after chest CT examination. Immediately, the health and epidemic prevention department of the ministry of health of Nanjing Military Command and the disease prevention and control center of the Nanjing Military Command received a phone call from Fuzhou General Hospital of PLA. Upon arrival, the prevention and control team conducted a series of epidemiological investigations and on-site prevention, control and disposal of the event, and conducted chest CT screening for other 289 students and staff who volunteered to be examined living in the same area. After the patients with similar pulmonary nodules shadow were screened out, mycoplasma antibody titer detection and chest CT re-scanning were performed for compliance patients. Results: There were 301 students living in the dormitories (Building A and B) of the student living area, and they were screened by chest CT, and it was found that 27 of them had pulmonary nodules shadow, including single pulmonary nodules shadow (48.1%, 13 out of 27) and multiple pulmonary nodules shadow (51.9%, 14 out of 27). And halo sign was observed in 25 of 27 patients (92.6%). The majority of the 27 patients were asymptomatic, only 2 patients got cough, a few of them had systemic symptoms such as fever, dizziness, fatigue. The positive rate of pulmonary nodules shadow was 32.8% (22/67) in building A (poor environmental hygiene), 2.14% (5/234) in building B, and the total incidence rate was 8.97%. Four-fold increase in the mycoplasma pneumoniae (MP) antibody titer in the paired sera was observed in first 12 patients. Measures such as disinfection, isolation and sanitation were taken to control the spread of the epidemic. There was no serious and death cases on the basis of active treatment on the affected patients. Conclusions: The outbreak of mycoplasma pneumoniae pneumonia often occur in crowded places. And the clinical and imaging features of mycoplasma pneumoniae pneumonia are atypical. Standard epidemiological intervention should be adopted for the sudden onset of respiratory diseases with unknown causes.

[Effects of different time of cryoablation on the proliferation of airway traumatic granuloma and its mechanism in rabbits].

Objective: To investigate the effect of different cryoablation time on tracheal traumatic granulation formation and its mechanism. Methods: A total of 32 rabbits were randomly assigned into four groups (A-D). Group A underwent tracheotomy alone. Group B, C and D received intra-tracheal brush rubbing to establish airway granulation model. Group C and D underwent 30 s and 2-minute cryoablation respectively. Tracheal specimens of all groups were collected to examine pathological changes using HE staining. Levels of transforming growth factor beta 1 (TGF-ß(1)) and CD34 in tracheal granulation were evaluated using immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT-qCR). Results: Tracheal lumens of group A were smooth without granulation. While the growth of granulation and luminal stenosis were most severe in Group B, followed by Group D and C. Submucosa thickness of Group B was largest as compared with other groups (0.20±0.07, 0.77±0.28, 0.44±0.13 and 0.55±0.18 mm for Group A to D, respectively. P<0.05). And the submucosa layer of Group C was thinner than Group D (P<0.05). The expression and transcription levels of TGF-ß(1) of trachea were highest in Group B as detected by IHC and RT-qPCR (P<0.05), followed by Group D and C (IHC: 0.48±0.01 vs 0.43±0.01, P<0.05; RT-qPCR: 12.61±2.14 vs 2.38±0.10, P<0.05). Both protein and mRNA levels of CD34 were highest in Group B as detected by IHC and RT-qPCR (P<0.05). Tracheal mRNA levels of CD34 were more abundant in Group D than Group C (4.92±0.90 vs 2.09±0.10, P<0.05), while no significant difference was found between groups regarding protein levels measured by IHC. Conclusions: Cryoablation could alleviate the hyperplasia of tracheal traumatic granulation, possibly due to the inhibition of TGF-ß(1) and CD34 expression. The effect of 30 s cryoablation for tracheal traumatic granulation is better.

[A clinican linical analysis of 29 cases of chronic pulmonary aspergillosis].

Objective: To improve the understanding of chronic pulmonary aspergillosis (CPA) by analyzing the clinical manifestations, imaging and pathological features, diagnosis, treatment and prognosis of this disease. Methods: Cases of CPA, proven by microbiological evidence based on pathological study in Fuzhou General Hospital of the People's Liberation Army and Affiliated Fuzhou City First Hospital of Fijian Medical University from January 2006 to October 2016 were retrospectively analyzed. Results: The patients consisted of 17 males and 12 females, aged 24 to 75 years, mean (42±16) years. The underlying disorders included post-tuberculosis infection (n=11), bronchiectasis (n=8), chronic obstructive pulmonary disease (n=3) and diabetes mellitus (n=2). The main clinical symptoms included productive cough (n=25), chronic sputum production (n=18) and hemoptysis (n=15). Serum GM antigen tests were performed in 19 cases, and the result was positive in 12 patients. BALF GM antigen tests were performed in 2 cases, both of which were positive. Chest CT showed that the lesions were located predominantly in the upper lobes (n=24). Single cavity with interior irregular intraluminal material (n=16) and multiple cavities with interior irregular intraluminal material (n=10) were the most frequent CT findings, while the "air crescent sign" was found in 13 cases. In the 22 patients who underwent surgical treatment, Aspergillus filaments were found in the cavity (n=20) or the bronchi (n=2) of lung samples, and histological examination didn't show tissue invasion by fungi. Surgical therapy was performed in 22 patients, with complete remission in 19 cases, and death in 3 cases. Anti-fungal therapy was administered in 6 patients, with partial remission in 4, and stable disease in 2 cases. One patient was not treated. Conclusions: CPA is more frequently seen in patients with underlying chronic pulmonary diseases. The common CT findings are single or multiple cavities with interior irregular intraluminal materials. Aspergillus filament in the cavity or bronchi of lung samples, without parenchymal invasion, is the proof of CPA. The surgical cure rate for simple aspergilloma and aspergillus nodule is high, while the risk of operation for chronic cavitary disease is high. GM antigen test may be an evidence for diagnosing CPA.

MicroRNA-154 functions as a tumor suppressor and directly targets HMGA2 in human non-small cell lung cancer.

MicroRNA-154 (miR-154) is dysregulated in some human malignancies and is correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Therefore, we explored the effects of miR-154 on NSCLC tumorigenesis and development. Using quantitative reverse transcription-polymerase chain reaction, we detected miR-154 expression in NSCLC cell lines and primary tumor tissues. The association between miR-154 expression and clinicopathological factors was investigated, and the effects of miR-154 on the biological behavior of NSCLC cells were examined. Ultimately, the potential regulatory effect of miR-154 on high-mobility group A2 protein (HMGA2) expression was confirmed. miR-154 was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR-154 expression was significantly associated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis confirmed that downregulation of miR-154 was an independent unfavorable prognostic factor for patients with NSCLC. Overexpression of miR-154 inhibited NSCLC cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. Furthermore, a luciferase reporter assay identified HMGA2 as a direct target of miR-154. Our findings indicate that miR-154 may act as a tumor suppressor in NSCLC and would serve as a novel therapeutic agent for miR-based therapy.

Chemistry of thiocarboxylates: synthesis and structures of neutral copper(I) thiocarboxylates with triphenylphosphine.

The reactions of Na+ R[O]CS- (R = Me, Ph) with mixtures of CuCl and PPh3 in stoichiometric ratios yielded the compounds [Cu4(SC[O]Me)4(PPh3)4] (1), [Cu4(SC[O]Ph)4(PPh3)3] (2), [Cu2(SC[O]Me)2(PPh3)4] (3), [Cu(SC[O]Ph)(PPh3)2] (4), and [Cu2(SC[O]Ph)2(PPh3)3] (5) quantitatively. Compound 2 was also obtained from mixtures of CuCl, PPh3, and NaSC[O]Ph in the ratio 1:1:1. The analogous thioacetate compound similar to 2 and the thiobenzoate analogue of 1 could not be obtained. Attempts to prepare the unsymmetrical dimer of a thioacetate compound similar to 5 gave a mixture of 1 and 3. The structures of 1-4 have been determined by single-crystal X-ray diffraction methods. Crystal data for 1: triclinic space group Pl, a = 11.5844(3) A, b = 13.2459(3) A, c = 14.3433(3) A, alpha = 64.019(1) degrees, beta = 79.297(1) degrees, gamma = 69.426(1) degrees, V = 1850.98(7) A3, Z = 1, Dcalcd = 1.439 g.cm-3. Crystal data for 2.0.5CH2Cl2.H2O: triclinic space group P1, a = 12.4413(1) A, b = 15.5443(1) A, c = 20.4637(3) A, alpha = 94.974(1) degrees, beta = 95.976(1) degrees, gamma = 100.450(1) degrees, V = 3848.09(7) A3, Z = 2, Dcalcd = 1.416 g.cm-3. Single-crystal data for 3: monoclinic space group P2(1)/n, a = 15.2746(2) A, b = 23.2947(2) A, c = 19.0518(3) A, beta = 96.713(1) degrees, V = 6732.5(2) A3, Z = 4, Dcalcd = 1.309 g.cm-3. Crystal data for 4: triclinic space group P1, a = 10.2524(3) A, b = 12.9826(4) A, c = 14.5340(4) A, alpha = 87.723(1) degrees, beta = 75.322(1) degrees, gamma = 75.978(1) degrees, V = 1815.14(9) A3, Z = 2, Dcalcd = 1.327 g.cm-3. Compound 1, [mu 3-SC[O]Me-S)2(mu-SC[O]Me-S)2(CuPPh3)4], is a tetramer with a distorted stepladder structure in which two copper atoms are trigonally coordinated and the other two are tetrahedrally coordinated. Two bonding modes, namely, mu 3-S and mu 2-S, were observed for the Me[O]CS- anion. The structure of 2 may be described as a highly distorted cubanoid structure and formulated as [(mu 3-SC[O]Ph-S3)(mu 3-SC[O]Ph-S2,O)3(Cu)(CuPPh3)3]. In 2, three copper atoms have tetrahedral coordination geometry and one copper atom is trigonally coordinated. Unprecedented bonding modes, namely, mu 3-S, have been observed for the R[O]CS- anions, in 1 and 2 and mu 3-S2,O in 2. Compound 3, [(mu-SC[O]MeS)(mu-SC[O]Me-S,O)[Cu(PPh3)2]2] is a dimer with mu 2-S and mu 2-S,O bonding modes of Me[O]CS- ligands. Monomeric structure was found in 4 in which the copper atom has trigonal planar geometry with a very weak intramolecular interaction with O. Variable temperature 31P NMR studies in solution show the presence of various species in equilibria.