[Improve the clinical research and standardize the management of pleural diseases].

Based on the clinical evidence obtained during the past decade, we reviewed herein the evidences in the treatment of 5 types of common pleural diseases. (1) Therapeutic pleural interventions are not recommended for patients with malignant pleural effusion (MPE) who are asymptomatic. In patients with symptomatic MPE, large-volume thoracentesis should be performed in MPE patients to figure out if the patient's symptoms are related to the effusion and/or if the lung is expandable; if so, indwelling pleural catheters and/or talc pleurodesis can be used as first-line definitive intervention. Indwelling pleural catheters, but not pleurodesis should be used in those with symptomatic MPE with nonexpandable lung, failed pleurodesis, or loculated effusion. (2) Randomized controlled trials concerning tuberculous pleurisy management are always scarce. Based on the data from pulmonary tuberculosis trials, it can be accepted that anti-tuberculosis treatment regimen for tuberculous pleurisy with isoniazid, rifampin, and pyrazinamide for two months followed by four months of two drugs, isoniazid and rifampin. (3) A combination of tissue plasminogen activator and deoxyribonuclease can be instilled intrapleurally as the initial treatment, or as a follow-up treatment after surgery for pleural infection. The recommended dosages are as follows: tissue plasminogen activator 10 mg, twice a day, deoxyribonuclease 5 mg, twice a day. (4) The randomized controlled trial has provided evidence that conservative management is an acceptable alternative to interventional management for moderate-to-large primary spontaneous pneumothorax. (5) For patients with malignant pleural mesothelioma, nivolumab plus ipilimumab is capable of significantly improving the overall survival of patients versus platinum plus pemetrexed chemotherapy, supporting the use of this regimen as the first-line treatment for these patients, regardless of histological subtype.

[Use of fibrinolytics and deoxyribonuclease in patients with pleural infection].

Just over a decade ago, it was widely accepted that intrapleural instillation of fibrinolytics was ineffective in treatment of pleural infection. Due to the accumulation of clinical study evidence, an expert team from several countries developed an international consensus and recommended that tissue plasminogen activator and deoxyribonuclease should be instilled intrapleurally at the same time as the initial treatment, or as a follow-up treatment after surgery for pleural infection. The recommended dosages are as follows: tissue plasminogen activator 10 mg, twice a day, deoxyribonuclease 5 mg, twice a day. The future researches should focus on optimizing the tissue plasminogen activator and deoxyribonuclease schemes and developing more effective fibrinolytics.

[Value of PET/MRI in the diagnosis of malignant pleural effusion in comparison with PET/CT].

Objective: To investigate the diagnostic value of PET/MRI for malignant pleural effusion (MPE), and compare its diagnostic difference with PET/CT. Methods: The data of 57 patients with suspected MPE admitted into Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2017 to January 2020 was analyzed. A total of 53 patients were included in the prospective study, and the whole body PET/CT and thoracic PET/MRI were performed on them respectively. Two physicians used a blind method to evaluate the morphological features of PET/CT and PET/MRI images, delineate the region of interest (ROI), obtain the maximum standard uptake value (SUVmax) of the ROI in the PET/CT and PET/MRI images. The target-to-background ratio (TBR) of the lesion was calculated. The diffusion-weighted imaging (DWI) characteristics of the pleura in PET/MRI images were analyzed. Taking pathological diagnosis as the gold standard, the diagnostic effect of PET/CT and PET/MRI on MPE were evaluated. Results: The 53 patients who were finally included were (62.8±1.7) years old, consisting of 31 males. Pathological results showed that 41 cases were MPE and 12 cases were benign pleural effusion (BPE). There were no statistical differences in age, gender and smoking history between the two groups (P>0.05). Bland-Altman analysis showed that the SUVmax of pleural lesions by PET/MRI was higher than that by PET/CT (6.4±0.6 vs 5.3±0.5, P<0.001). The TBR of PET/MRI was higher than that of PET/CT (2.2±0.2 vs 1.8±0.2, P<0.001). The sensitivity, specificity, and accuracy of PET/MRI in the diagnosis of MPE by combining imaging features such as SUVmax and DWI of pleural lesions were 75.6%, 100%, and 81.1%, respectively. The sensitivity, specificity, and accuracy of PET/CT combined with SUVmax and imaging features of pleural lesions in the diagnosis of MPE were 85.4%, 83.3%, and 77.4%, respectively. There was no statistically significant difference between PET/MRI and PET/CT in the area under the curve (AUC) for diagnosing MPE (0.934 vs 0.873, P>0.05). Conclusions: PET/MRI and PET/CT have the equivalent diagnostic efficiency for MPE. However, PET/MRI shows higher SUVmax and TBR for pleural lesions, and has specific pleural DWI imaging characteristics, which is worthy of further clinical research.

Extracellular Vesicles of GMSCs Alleviate Aging-Related Cell Senescence.

Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress-induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials. Our results showed that GMSC-EVs robustly abrogated oxidative stress-induced upregulation in the expression of cellular senescence-related genes, such as ß-galactosidase, p21, p53, and γH2AX, and mTOR/pS6 signaling pathway, in human umbilical vein endothelial cells (HUVECs) and skin fibroblasts. Meanwhile, GMSC-EVs restored oxidative stress-induced impairment in proliferation and tube formation by HUVECs. Systemic administration of GMSC-EVs attenuated aging-associated elevation in the expression levels of p21, mTOR/pS6, interleukin 6, and tumor necrosis factor α in skin and heart tissues of aged mice. These findings suggest that GMSC-EVs could be a potential alternative source of cell-free product for attenuation of aging-related skin and vascular dysfunctions due to their potent inhibitory effects on oxidative stress-induced cellular senescence in endothelial cells and skin fibroblasts.

MicroRNA-362 inhibits cell growth and metastasis in glioblastoma by targeting MAPK1.

OBJECTIVE: Glioblastoma (GBM) is a deadly brain cancer that seriously threatens the lives of patients. Moreover, various microRNAs (miRNAs) have been found to be involved in the progression of GBM. The purpose of this study is to preliminarily elucidate the regulatory mechanism of miR-362 in GBM. PATIENTS AND METHODS: The abnormal expression of miR-362 and MAPK1 was detected by RT-qPCR or Western blot analysis in GBM tissues and cells. CCK-8 and transwell assays were performed to measure cell proliferation, migration and invasion. The relationship between miR-362 and MAPK1 was confirmed by luciferase reporter assay. RESULTS: MiR-362 expression was reduced in GBM tissues and cells. The decreased expression of miR-362 predicted poor prognosis in GBM patients. Functionally, overexpression of miR-362 inhibited the proliferation and metastasis of GBM cells. In addition, miR-362 directly targets MAPK1. MAPK1 was negatively correlated with miR-362 expression in GBM. Moreover, MAPK1 was upregulated and served as a tumor promoter in GBM. More importantly, the upregulation of MAPK1 weakened the inhibitory effect of miR-362 on cell proliferation and metastasis in GBM. CONCLUSIONS: MiR-362 restrains cell proliferation and metastasis in GBM by targeting MAPK1, indicating that miR-362 functions as a tumor suppressor in GBM.

The diagnostic and prognostic values of serum and urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in sepsis induced acute renal injury patients.

OBJECTIVE: The kidney injury molecule-1 (uKIM-1) and neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) have been demonstrated to be diagnostic biomarkers for acute kidney injury (AKI) in a variety of diseases. However, both of them were not well validated in sepsis patients with acute kidney injury. PATIENTS AND METHODS: This was a prospective and observational study which was performed in the three intensive care units of the Beijing Chao-Yang Hospital. Over a 12-month period, 174 patients (70 sepsis patients, 69 sepsis with AKI and 35 controls) were enrolled. Blood and urinary specimens were collected at admission as soon as possible (within 24 hours) and KIM-1 and NGAL levels were tested. RESULTS: Levels of uKIM-1, uNGAL, sNGAL were significantly higher in the sepsis patients who developed AKI compared to those sepsis with no-AKI (0.88 ng/ml (0.37, 2.14) vs. 1.21 ng/ml (0.67, 3.26) p=0.003, 63.54 ng/ml (21.66, 125.45) vs. 249.85 ng/ml (86.60, 585.97) p<0.001, and 108.08 ng/ml (67.74, 212.22) vs. 200.01 ng/ml (102.76, 300.77) p=0.001, respectively). sKIM-1 also had significant differences between the two groups (83.98 pg/ml (54.00,147.08) vs. 193.41 pg/ml (106.90, 430.60) p<0.001). The four biomarkers (uKIM-1, sKIM-1, uNGAL, sNGAL) all could be predictive for AKI, and the areas under the receiver operating characteristic curves (AUROC) were 0.607, 0.754, 0.768, 0.658, respectively. The uNGAL was an independent risk factor for septic AKI, and the AUROC was 0.768 (95% CI: 0.689 to 0.835). The uNGAL and sNGAL were related to the prognosis of sepsis. CONCLUSIONS: Our results showed that NGAL was a promising biomarker of septic AKI. Like the uKIM-1, the sKIM-1 could early predict the occurrence of septic AKI too, but both of them did not have the predictive value in judging the severity of AKI and the prognosis of sepsis.

miR-135a inhibits glioma cell proliferation and invasion by directly targeting FOXO1.

OBJECTIVE: To investigate the potential function of miR-135a in glioma. PATIENTS AND METHODS: A total of 50 pairs of glioma tissue samples and para-carcinoma tissue samples were collected. Human glioma cell line (U251) and normal human astrocyte (NHA) were cultured. The expression of RNA and protein was detected by quantitative Real time-polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell proliferation assay and transwell assay were used to detect the activities of proliferation and invasion. Luciferase reporter assays were carried out to determine the binding efficiency between forkhead box O1 (FOXO1) and miR-135a in U251 cells. RESULTS: qRT-PCR results showed that miR-135a expression was significantly reduced while FOXO1 was up-regulated in glioma tissues. miR-135a overexpression in U251 cells could prominently inhibit proliferation and invasion according to the transwell assays. Moreover, FOXO1 was recognized as the target for miR-135a and may partially reverse the functions of miR-135a in U251 cells. CONCLUSIONS: We showed that miR-135a inhibits glioma cell proliferation and invasion by down-regulating the target gene FOXO1.

MicroRNA-378 acts as a prognosis marker and inhibits cell migration, invasion and epithelial-mesenchymal transition in human glioma by targeting IRG1.

OBJECTIVE: Glioma is one common intracranial malignancy. Recently, there has been a large volume of published studies describing the functions of microRNAs as potential diagnostic markers for glioma. Data from several sources revealed that miR-378 played crucial roles in multiple tumors. However, much uncertainty still exists about the functions and underlying mechanism of miR-378. The purpose of the present work was to evaluate the potential effect of miR-378 and verify its influence on the function of IRG1 in glioma. PATIENTS AND METHODS: The miR-378 expression was examined in 52 pairs of glioma tissues using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Transwell assays were conducted to detect the capability of glioma cell migration and invasion with different transfections. Luciferase reporter was used to confirm whether miR-378 could regulate immune responsive gene 1 (IRG1). Western blot was used to measure the expressions of EMT-related markers. RESULTS: miR 378 expressions were notably reduced in glioma cells and tissues in comparison with controls. The declined miR-378 expressions were correlated with the poor OS and worse clinicopathological parameters of glioma patients. Overexpression of miR-378 repressed glioma cell epithelial-mesenchymal transition (EMT) and metastasis as well as the tumor growth rate and tumor size of glioma mice. Additionally, IRG1 was markedly up-regulated in glioma and was confirmed as a direct target for miR 378 in glioma. CONCLUSIONS: We showed that the suppressive role of miR-378 in glioma, which was regulated by IRG1, suggested that the miR-378/IRG1 axis may be an effective target for glioma treatment.

An experimental system for coiled tubing partial underbalanced drilling (CT-PUBD) technique.

To improve the rate of penetration (ROP) in hard formations, a new high-speed drilling technique called Coiled Tubing Partial Underbalanced Drilling (CT-PUBD) is proposed. This method uses a rotary packer to realize an underbalanced condition near the bit by creating a micro-annulus and an overbalanced condition at the main part of the annulus. A new full-scale laboratory experimental system is designed and set up to study the hydraulic characteristics and drilling performance of this method. The system is composed of a drilling system, circulation system, and monitor system, including three key devices, namely, cuttings discharge device, rotary packer, and backflow device. The experimental results showed that the pressure loss increased linearly with the flow rate of the drilling fluid. The high drilling speed of CT-PUBD proved it a better drilling method than the conventional drilling. The experimental system may provide a fundamental basis for the research of CT-PUBD, and the results proved that this new method is feasible in enhancing ROP and guaranteeing the drilling safety.

[Primary renal lymphoma: a clinical analysis of 5 cases].

Objective: To improve the clinical diagnosis and treatment of primary renal lymphoma. Methods: Clinical data of 5 cases ( 2 male cases and 3 female cases) with primary renal lymphoma was reviewed. The age of patients was 55 to 70 years old, with a mean age of 62 years. No history of glomerulonephritis or nephropathy was recorded. All the cases were unilateral, including 3 cases in the left side and 2 cases in right. The major clinical manifestations were as follows: 2 cases of left lumbar pain, 1 case of gross hematuria, 1 case of hematuria under microscope, and 1 case receiving adjuvant chemotherapy after 12 years. The physical examination was as follows: the superficial lymph nodes of 5 cases were not enlarged; the liver, spleen and abdominal mass were not palpable; 2 cases had left upper quadrant tenderness ( with no rebound pain) and left kidney percussion pain. B-ultrasound, CT or MRI examination were performed before the operation, and renal malignant neoplasm was considered. No abnormality was found in bone marrow aspiration after operation. Four cases underwent radical nephrectomy and 1 case accepted partial nephrectomy. Four cases were administered with six cycles of R-CHOP (cyclophosphamide, pirarubicin, vincristine and prednisone) associated with rituximab, and 1 case was given six cycles of CHOP. Results: Five cases were diagnosed as non-Hodgkin's lymphoma, with 4 cases of diffuse large B-cell lymphoma of the kidney and 1 case of marginal zone B-cell non-Hodgkin lymphoma of mucosa-associated lymphoid tissue. The maximum diameter of the tumor was 3.5 to 10 cm, with the median diameter of 6.5 cm. The tumor was grey and white on the cutting surface, and the texture was fine. Under the microscope, the tumor cells were diffusely infiltrating, oval or polygonal, slightly larger than normal lymphocytes, with large irregular hyperchromatic nuclei. Four cases were followed up for 6 months to 2 years, with an average of 16 months. Chest X - ray and abdominal B-ultrasound were performed every 3 months, and abdominal CT or MRI scan was performed every 6 months. One case lost follow-up after 3 months. Except the case, the rest three are all alive. Conclusions: Primary renal lymphoma is rare. Most of the cases reported showed rapid systemic progression and a poor prognosis. There were no distinct characteristics in B-ultrasound and CT examination. Pathological examination is the key to its diagnosis. The surgical treatment combined with systemic chemotherapy can prolong survival of patients.

[Clinical experience in diagnosis and treatment of primary retroperitoneal liposarcoma].

Objective: To summarize the experience in diagnosis and treatment of primary retroperitoneal liposarcoma. Methods: The clinic data of 73 cases of primary retroperitoneal liposarcoma were reviewed. The age of patients was 23 to 75 years old, with a median age of 53 years. Forty-five cases were treated for the first time, and 28 cases were re-treated after local recurrence. All patients underwent ultrasonography, CT or MRI before operation and were diagnosed of primary retroperitoneal liposarcoma. Results: No lymph node and distant metastasis were found in all patients. The maximum diameter of the tumor was 3-40 cm, with a median diameter of 18.9 cm. Of the 45 patients with primary treatment, 6 patients were in T2 stage and 39 in T3 stage. Of the 28 patients with retreatment after local recurrence, 4 patients were in T1, 8 in T2, and 16 in T3 stage. All the 73 patients received surgery, 7 were treated with adjuvant radiotherapy, and 3 received adjuvant chemotherapy. One hundred and ten operations were performed in 73 patients. Sixty-seven cases were diagnosed of well differentiated liposarcoma, with 60 cases of lipoma-like liposarcoma and 7 cases of sclerosing liposarcoma. Nine cases were diagnosed of dedifferentiated liposarcoma, 16 cases were myxoid liposarcoma, and 2 cases were pleomorphic liposarcoma. Sixteen cases were mixed types. A total of 69 cases were followed up for 6 months to 13 years, with an average of 4 years. Sixty-six cases obtained complete resection, 34 cases relapsed, and the recurrence rate was 51.5% (34/66). Distant metastasis occurred in 4 cases. Fourteen cases died of tumor recurrence or distant metastasis and the rest were all alive. Four cases lost follow-up after 3 months. No matter in the initial treatment group or the retreatment group, the recurrence rate of combined organ resection is lower than that of simple tumor resection, and the average recurrence time was longer. Results: Primary retroperitoneal liposarcoma was rare in clinical experience. CT is the most effective method in the diagnosis of retroperitoneal liposarcoma, however pathological examination was still the key to the diagnosis. The main treatment of retroperitoneal liposarcoma was surgical resection. Complete resection was the objective of the operation, and the combined viscera resection was performed for those with invasion of other organs. Retroperitoneal liposarcoma had the characteristics of local recurrence after operation and insensitivity to radiotherapy and chemotherapy, but the recurrent tumor can still be resected.

[Retrospective analysis of 13 cases of nocardiosis].

Objective: To evaluate the clinical features, chest radiological manifestations, microbiological examination and treatments of nocardial disease. Methods: A retrospective study was conducted to analyze the data of patients with nocardial infection admitted to Beijing Chaoyang Hospital from January 2010 to January 2016. Results: The 13 patients, 6 males and 7 females, aged (51±17) years. Twelve cases were diagnosed with pulmonary nocardiosis, and 1 with disseminated nocardial infection. Most of these patients had complications: autoimmune diseases in 3 (2 with autoimmune hemolytic anemia and 1 with systemic lupus erythematosus), and bronchiectasis in 6 patients. The most common symptoms were cough, expectoration and fever. The main manifestations of CT scans included nodules or masses, bronchiectasis, ground glass opacity, cavity and pleural thickening. Six cases were confirmed by sputum smear microscopy, 4 by bronchoalveolar lavage, 2 by percutaneous lung biopsy and 1 by renal abscess puncture. After diagnosis, antibiotics such as Co-trimoxazole, amikacin, cephalosporins, imipenem, minomycin, or linezolid were used, and the 13 patients were all cured and discharged. Conclusions: Pulmonary nocardiosis was the most common clinical presentation of nocardial infection. Cough, expectoration and fever were the most common symptoms. The main findings of CT scans were nodules or masses, bronchiectasis, ground glass opacity, cavity and pleural thickening. The diagnosis of nocardiosis was not easy because of the non-specific clinical presentations and difficult culture of nocardia spp. Thus, high clinical suspicion of nocardiosis is necessary for earlier diagnosis and treatment.

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. OBJECTIVE: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism. METHODS: The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed. RESULTS: Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.

[A multicenter study on the prognostic factors of one year outcomes in patients with poor grade intracranial aneurysm after early treatment].

OBJECTIVES: To explore the one year outcome of subarachnoid hemorrhage (SAH) patients with poor grade intracranial aneurysm who underwent early treatment (within 72 hours), and to analyze the possible predictors of the prognosis. METHODS: This clinical study was a prospective, multicenter, observational registry of SAH patients with poor grade intracranial aneurysm. Data pertaining to 203 SAH patients with poor grade intracranial aneurysm between October 2010 and March 2013 from 10 medical centers. There were 100 male and 103 female patients. Neurological outcomes at 12 months after the surgery were measured using the Glasgow Outcome Scale (GOS). Genders, age, smoke, breath, herniation, aneurysm location, World Federation of Neurosurgical Societies (WFNS) grade, CT Fisher's grade, alcohol consumption, aneurysm diameter, surgical procedure and operation time were identified as possible prognostic factors, the association between possible prognostic factors and outcome were analyzed, using univariate and multivariate analysis. Univariate analysis included Wilcoxon rank sum test, Kruskal-Wallis H test and Nemenyi test, multivariate analysis included Logistic regression test. RESULTS: Among 203 patients, 94 patients were WFNS grade Ⅳ, and 109 patients were WFNS grade Ⅴ; 31 patients were CT Fisher's grade 1 to 2, 172 patients were CT Fisher's grade 3 to 5. Herniation (OR=2.535, 95%CI: 1.204 to 5.339, P=0.014), WFNS grade Ⅴ (OR=3.728, 95%CI: 1.972 to 7.043, P=0.000), CT Fisher's grade 3 to 5 (OR=5.641, 95%CI: 2.032 to 15.643, P=0.001), and anterior circulation location (OR=6.234, 95%CI: 1.996 to 19.472, P=0.002) were found to be independent prognostic factors of unfavorable prognosis. CONCLUSIONS: Early surgical treatment could improve the prognosis of SAH patients with poor-grade-aneurysm. The patients with herniation, WFNS grade Ⅴ, CT Fisher's grade 3 to 5, anterior circulation aneurysms suffered unfavorable prognosis.