Clinic information, pathological, and imaging characteristics in 2 058 surgical patients with lung cancer from a single center. / 单中心2 058ä¾‹è‚ºç™Œæ‰‹æœ¯æ‚£è€ çš„ä¸´åºŠä¿¡æ¯ã€ç— ç†åŠå½±åƒå­¦ç‰¹å¾.

OBJECTIVES: Lung cancer is characterized by its high incidence and case fatality rate. Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer. This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information, pathological, and imaging characteristics of surgical patients with lung cancer. METHODS: The data of 2 058 patients, who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019, were retrospectively collected to analyze changes in clinic information, pathological, and imaging characteristics. RESULTS: From 2016 to 2019, the number of patients per year was 280, 376, 524, and 878, respectively. Adenocarcinoma (68.1%) was the most common pathological type of surgical patients with lung cancer. From 2016 to 2019, the proportion of adenocarcinoma was increased from 55.5% to 74.1%. The proportion lung cancer patients in stage IA was increased from 38.9% to 62.3%, and the proportion of patients who underwent sublobar resection was increased from 1.8% to 8.6%. The proportion of lymph node sampling was increased in 2019. Compared with the rate in 2016, the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved (2.0% vs 18.2%), and the detection rate of nodules with diameter>3 cm was decreased (34.7% vs 18.3%). From 2016 to 2019, the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0% and 16.6% to 20.0% and 37.3%, respectively. The proportion of solid density was decreased from 81.4% to 42.7%. CONCLUSIONS: The number of lung cancer surgery patients is rapidly increasing year by year, the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing, the proportion of patients with adenocarcinoma is rising, the proportion of early-stage lung cancer is increasing, smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.

Ningxin-Tongyu-Zishen formula alleviates the senescence of granulosa cells on D-galactose-induced premature ovarian insufficiency mice.

Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For in vivo experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For in vitro experiments, H2O2 (200 µM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 µM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. In vivo, NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. In vitro experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.

PD-1/PD-L1 inhibitor treatment and its impact on clinical imaging in non-small cell lung cancer: a systematic review and meta-analysis of immune-related adverse events.

Background: In the contemporary era of cancer treatment, lung cancer (LC) holds the unenviable position of being the primary contributor to cancer-induced mortality worldwide. Although immunotherapy has expanded the therapeutic landscape for metastatic non-small cell lung cancer (NSCLC), the advent of immune checkpoint inhibitors has been accompanied by a concomitant increase in immune-related adverse events (irAEs). Timely detection of irAEs is pivotal for efficacious management and enhanced patient outcomes. Diagnostic imaging, encompassing x-ray and CT scans, can facilitate the identification and supervision of irAEs, thereby ensuring the prompt recognition of associated patterns and alterations for expeditious treatment. Methods: The present inquiry undertook a systematic exploration of multiple databases, incorporating a diverse array of studies such as randomized controlled trials and observational analyses. Patient demographics, imaging outcomes, and risk of bias were extracted from the data. Meta-analysis was executed utilizing R Statistical Software, with the results of the risk of bias assessment summarized accordingly. Findings: The analysis unveiled a higher prevalence of irAEs in patients receiving first-line treatment for NSCLC compared to those receiving subsequent treatments, with a statistically significant distinction observed for both high- and low-grade irAEs (p < 0.001). Pneumonitis, thyroiditis, and colitis emerged as the most frequently reported irAEs, whereas hepatitis and pancolitis were less commonly documented. This investigation signifies a crucial advancement in elucidating the function of imaging in the treatment of NSCLC with PD-1/PD-L1 inhibitors and emphasizes the imperative for ongoing research in this domain.

IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B-cell lymphoma.

PURPOSE: Large B-cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. METHODS: The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. RESULTS: Twenty-one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium-sized blastoid cytology, germinal center B-cell-like, and CD5+ phenotype, compared with IRF4- ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4- ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. CONCLUSION: Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy.

Preliminary results of low-dose computed tomography screening for lung cancer in asymptomatic participants. / 低剂量CTç­›æŸ¥æ— ç—‡çŠ¶ä½“æ£€è€ è‚ºç™Œçš„åˆæ­¥åˆ†æž.

OBJECTIVES: Low dose computed tomography (LDCT) is the best method for early diagnosis of lung cancer. Even though it has been widely used in clinic, the selection of screening objects and the management scheme of pulmonary nodules are still not unified among research institutions. This study aims to evaluate the effect of LDCT in detection effect and follow-up process for pulmonary nodules in asymptomatic participants. METHODS: A total of 1 600 asymptomatic participants (37 to 82 years old), who came from Yantian District People's Hospital, Southern University of Science and Technology, received LDCT. The lung nodules were categorized into positive nodules and semi-positive nodules, and according to the density of positive nodules they were categorized into 4 types: solid nodules (SN), partial solid nodules (pSN), pure ground glass nodules (pGGN), and pleural nodules (PN). The number, detection rate, imaging findings, follow-up change of lung nodules, and the postoperative pathological results of positive nodules were recorded and analyzed. RESULTS: Lung nodules were found in 221 cases by LDCT. The total detection rate of lung nodule was 13.8% (221/1 600), and the detection rate in positive nodules was 4.9% (79/1 600). The detected nodules were mainly single (173 cases), solid (133 cases) and semi-positive nodules (142 cases). Most of nodules (177 cases) had no change in the follow-up process. The enlargement and/or increased density of nodules (5 cases) were lung cancer. Pathological results were obtained in 10 cases, 8 cases were malignant (1 small cell lung cancer and 7 adenocarcinomas), 2 cases were benign (cryptococcal infection and alveolar epithelial dysplasia). The detection rate of lung cancer was 0.5% (8/1 600), and the proportion of early lung cancer was 75% (6/8). CONCLUSIONS: LDCT screening can identify and increase the detection rate in the early lung cancer, which is an effective screening method. It is safe and feasible to take regular follow-up and re-examination for nodules with diameter less than 5 mm. When the size and or density of nodule increases, it indicates the malignant prognosis of the nodule and timely clinical intervention is needed.

Imaging evaluation of lung cancer treated with PD-1/PD-L1 inhibitors.

Immunotherapy (PD-1/PD-L1 inhibitors) has attracted attention for lung cancer treatment and recasted the administration of immunotherapeutics to patients who have advanced/metastatic diseases. Whether in combination or as monotherapy, these medications have become common therapies for certain patients with lung cancer. Moreover, their usage is expected to expand widely in the future. This review aims to discuss the imaging evaluation of lung cancer response to PD-1/PD-L1 therapy with focus on new radiological criteria for immunotherapy response. Abnormal radiological responses (pseudoprogression, dissociative responses, and hyperprogression) and immune-related adverse events are also described.

Correlation Between Pulmonary Sclerosing Pneumocytoma Features and MSCT Imaging Manifestations in 34 Patients: Implications for Precision Medicine.

Objective: To identify and analyze the multi-slice computed tomography (MSCT) imaging manifestations and clinicopathological features of PSP to improve the preoperative and intraoperative diagnosis of the disease. Method: This was a retrospective study conducted on the imaging and clinicopathological data of the PSP patients treated in two major hospitals in China from October 2001 to December 2019. The locations of lung lesions, clinical symptoms, surgical complications, MSCT imaging features, and the corresponding relationship with clinicopathological features were assessed. Then, a new diagnostic approach was defined and used to train imaging and pathological doctors (experimental group). Then, the diagnostic accuracy of the experimental group was evaluated in preoperative and intraoperative diagnosis of PSP. Results: Thirty-four PSP cases were analyzed (mean: 51.42; range: 39-69 years old). The peripheral type was more common, while 92% of the lesions located in the middle lobe of the right lung and the lower lobe of bilateral lungs. The shortest lesion edge-pleura distance ranged 0 to 30 mm and 46% of the lesions (16/34) were attached to the pleura, 62% (21/34) located at 0-5 mm, 92% (31/34) within 20 mm from the pleura. Diameters of the lesions ranged 8.58 to 68.41 mm, while most of them were 20-40 mm. All lesions showed enhancement, and 97% (33/34) were unevenly enhanced. PSP volume was negatively correlated with the total degree of enhancement (r = -0.587, p < 0.01), and the volume difference between the obvious enhancement zone and the slight enhancement zone (r = -0.795, p < 0.01). Welt vessel sign was observed in 61.7% (21/34) of cases, and none of welt vessels entered into the lesions. Vascular-like enhancement area inside the lesion showed no significant correlation with the welt vessels outside the lesion, and no case showed entrance of bronchus into the lesion. The trained experimental group showed significantly greater diagnostic accuracy than the control group. In particular, the accuracy rate of intraoperative frozen section diagnosis was 60% higher in the experimental group than the control group. Conclusion: PSP has characteristic imaging manifestations, which can be utilized to improve the preoperative and intraoperative diagnostic coincidence rate of PSP.

The clinicopathological relevance of uniform CD56 expression in anaplastic large cell lymphoma: a retrospective analysis of 18 cases.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) with uniform CD56 expression is a rare condition, that has been described in limited literature, and its clinicopathological features have not yet been well illustrated. The aim of our study was to fully investigate the clinical, histological, immunohistochemical and molecular features of CD56+ ALCL. METHODS: The clinical and histological characteristics of CD56+ ALCL cases were retrospectively evaluated. The immunohistochemical phenotype, status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. Overall survival was also analyzed. RESULTS: Eighteen (5.8%) cases with diffuse CD56 expression were identified out of 313 archived ALCL cases with CD56 test. CD56 expression was significantly higher in ALK+ systemic ALCLs (sALCLs) (13/64, 20.3%) than in ALK- sALCLs (3/101, 3.0%) (p < 0.001) as well as primary cutaneous ALCLs (2/148, 1.4%) (p < 0.001). Regarding the CD56+ ALK+ sALCLs, the median age was 20 years (range, 8-60 years) with a male-to-female ratio of 2.3:1, and these cases more frequently affected extranodal sites (11/38, 28.9%) rather than lymph nodes (2/26, 7.7%) (p = 0.038). Eleven (84.6%) cases presented with stage I-II diseases, which was significantly more than their CD56- ALK+ counterparts (45.5%) (p = 0.015). Histologically, 2 ALK+ cases were of small cell variant and all the others displayed characteristic morphology of classic ALCL. Regarding the immunophenotype, both CD30 and CD56 were diffusely positive in all cases. CD3, CD43, anaplastic lymphoma kinase-1 (ALK1), TIA-1, EMA expression was observed in 30.8% (4/13), 90.9% (10/11), 100% (13/13), 100% (9/9), and 80.0% (8/10) cases, respectively. EBV infection was consistently absent. Monoclonal TCR gene rearrangement was found in 100% (5/5) of investigated ALK+ cases. Chemotherapy with a CHOP regimen was most frequently employed. The 3-year overall survival (OS) rate for CD56+ ALK+ patients was 92.0%, compared with 73.0% for their CD56- counterparts, but there was no significant difference in OS between the two groups (p = 0.264). CONCLUSIONS: Uniform CD56 expression is an unexpected condition in ALCL. Of ALK+ ALCLs, CD56 expression correlated with a high frequency of early stage and an extranodal predominance. It is of great importance to raise awareness of this condition and familiarity with its characteristic features to avoid diagnostic and therapeutic pitfalls. Further investigations are warranted for a better understanding of this unusual phenotype and the significance of CD56 expression in ALCL.

Epigallocatechin-3-gallate-induced vascular normalization in A549-cell xenograft-bearing nude mice: therapeutic efficacy in combination with chemotherapy.

PURPOSE: Large-scale studies have revealed that appropriate antiangiogenic treatment enables the recovery of the normal structure and function of solid tumor vessels. Epigallocatechin-3-gallate (EGCG), a natural extract of green tea, has multiple effects on angiogenesis. However, normalization of blood vessels due to natural ingredients has not yet been reported. Therefore, we examined the microvasculature, microenvironment, and efficacy of EGCG combined with chemotherapy in a xenograft model. METHODS: We treated A549 cell (human lung adenocarcinoma cell line) xenograft-bearing nude mice with EGCG in vivo. CD31, αSMA, and collagen IV were labeled and detected using quantum-dot double-labeled immunofluorescence to measure microvessel density, microvessel pericyte-coverage index, and collagen IV expression. Vessel-perfusion function was determined by lectin injection, permeability by Evans blue extravasation, interstitial fluid pressure using the wick-in-needle technique, and hypoxia levels using a polarographic electrode and immunohistochemical pimonidazole labeling. Cisplatin concentration in tumor tissue was detected using graphite-furnace atomic absorption spectrophotometry. Xenograft mice were randomized into five groups: treated with saline, cisplatin, EGCG, EGCG + cisplatin on day 1, or EGCG + cisplatin during the vascular normalization window. Tumor-growth delay and tumor-suppression rate were measured to evaluate tumor growth. RESULTS: EGCG treatment in vivo caused temporary changes, including transient depression of microvessel density, microvessel pericyte-coverage index, and collagen IV expression, transient elevation of vessel perfusion and permeability, and decreased interstitial fluid pressure and hypoxia. During vascular normalization, pretreatment with EGCG increased cisplatin concentration in tumor tissue compared with treatment with cisplatin only. Tumor-growth delay after treatment in the five groups during the vascular normalization window was 6.3±1.51, 7.5±1.57, 8.3±1.79, 12.1±1.35, and 15.4±1.99 days, indicating synergistic EGCG-cisplatin effects, especially during the vascular normalization window (P<0.01). CONCLUSION: EGCG-induced vascular normalization in human lung adenocarcinoma may be a novel modality for enhancing chemotherapy effects.

Evaluation of the mechanisms and effects of Mg-Ag-Y alloy on the tumor growth and metastasis of the MG63 osteosarcoma cell line.

Osteosarcoma is a malignant primary bone tumor, which often associates with pulmonary metastasis. The radical surgery of osteosarcoma often requires internal orthopedic implants. Therefore, implants with antitumor properties should be developed. Magnesium (Mg) and its alloys possess great potential as orthopedic materials, given their biodegradable properties, superior osteogenesis performance, and antitumor features. However, problems arise with their uncontrolled degradation rates and their unknown antitumor mechanisms. In our study, when compared with pure Mg, the rare element silver alloyed with yttrium (Ag-Y) could extremely enhance the corrosion resistance of these elements, giving the Ex-Mg-1Ag-1Y alloy better anticorrosion rates. Here, we implanted the Ex-Mg-1Ag-1Y alloy and pure Mg and Ti alloy in vivo around tumors in nude mice (BALB/c). Notably, the local tumor weight in Mg alloy and pure Mg groups were much smaller than that in Ti alloy group in 36 days after surgery (6.59 ± 0.70, 6.76 ± 0.62, and 8.54 ± 0.56 g), while the general scores of lung metastasis in Mg alloy and pure Mg groups were also lower than Ti alloy group (64.50 ± 7.64, 62.73 ± 7.84, and 87.60 ± 9.43). Therefore, the Mg and Ex-Mg-1Ag-1Y alloy, both demonstrated resisting effects against local tumor growth and pulmonary metastasis, which could be performed by changing the extracellular acidosis microenvironment, elevating the Mg concentration, suppressing C-X-C chemokine receptor type 4 (CXCR4) levels, and increasing prostacyclin (PGI2 ) synthesis. Our work revealed that the Ex-Mg-1Ag-1Y alloy may be a promising orthopedic implant for treating osteosarcoma due to its better corrosion resistance and antitumor attributes. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2537-2548, 2019.

[Manifestations of the connective tissue associated interstitial lung disease under high resolution computed tomography].

OBJECTIVE: To analyze the features of the connective tissue associated interstitial lung disease (CTD-ILD) by high resolution computed tomography (HRCT).
 Methods: A total of 127 patients with CTD-ILD, who were diagnosed by clinic laboratory examination and pathology in Xiangya Hospital of Central South University form September 2013 to September 2015, were enrolled for this study. Their lung features of HRCT imaging were retrospectively analyzed.
 Results: The classifications for 127 patients were as follows: 36 cases of rheumatoid arthritis (28.3%), 34 cases of dermatomyositis and polymyositis (26.8%), 31 cases of systemic sclerosis (24.4%), 18 cases of Sjögren syndrome (14.2%), 7 cases of mixed connective tissue disease (5.5%), and 1 cases of systemic lupus erythematosus (0.8%). According to the features of HRCT imaging, the patients were divided as follows: 77 cases (60.6%) of nonspecific interstitial pneumonia (NSIP), 46 cases (36.2%) of usual interstitial pneumonia (UIP), 2 cases (1.6%) of lymphocytic interstitial pneumonia (LIP), 1 case (0.8%) of cryptogenic interstitial pneumonia (COP), and 1 case (0.8%) of acute interstitial pneumonia (AIP). The HRCT findings for 36 cases of rheumatoid arthritis associated interstitial lung disease were UIP (24 cases, 66.7%) and NSIP (12 cases, 33.3%); the HRCT findings for 34 cases of dermatomyositis and polymyositis associated interstitial lung disease were NSIP (32 cases, 94.1%), UIP (1 case, 2.9%) and COP (1 case, 2.9%); the HRCT findings for 31 cases of systemic sclerosis associated interstitial lung disease were NSIP (21 cases, 67.8%), UIP (9 cases, 29%), LIP(1 case, 3.2%); the HRCT findings for 18 cases of Sjögren syndrome associated interstitial lung disease were NSIP (9 cases, 50.0%), UIP (8 cases, 44.4%), LIP (1 case, 5.6%); the HRCT findings for 7 cases of mixed connective tissue disease associated interstitial lung disease were UIP (4 cases, 57.1%), NSIP (3 cases, 42.9%). SLE-ILD was rare, with only 1 case of AIP.
 Conclusion: Different types of CTD-ILD patients display relatively unique manifestation of HRCT.

[Methods for establishing animal model of bronchopulmonary dysplasia and their evaluation].

With the development of treatment, the survival rate of premature infants has significantly increased, especially extremely premature infants and very low birth weight infants. This has led to an increase in incidence of bronchopulmonary dysplasia (BPD) year by year. BPD has been one of the most common respiratory system diseases in premature infants, especially the small premature infants. Arrested alveolar development is an important cause of BPD. Therefore, the mechanism of arrested alveolar development and the intervention measures for promoting alveolar development are the focuses of research on BPD. Selecting the appropriate animal model of BPD is the key to obtaining meaningful results in the basic research on BPD. Based on above, several common methods for establishing an animal model of BPD and the corresponding changes in pathophysiology are summarized and evaluated in order to provide a reference for selecting the appropriate animal model in studies on the pathogenesis, pathophysiology, and prevention and control strategies of BPD.

Primary Intestinal Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Comprehensive Clinicopathological Analysis of 55 Cases.

PURPOSE: To investigate the clinicopathological features, survival and prognostic factors of primary intestinal extranodal natural killer/T-cell lymphoma, nasal type (PI-ENKTCL). METHODS: Clinical and histological characteristics of PI-ENKTCL cases were retrospectively evaluated. Immunohistochemical phenotype and status of Epstein-Barr virus (EBV) and T-cell receptor (TCR) gene rearrangement were examined. The overall survival and prognostic parameters were also analyzed. RESULTS: Fifty-five (2.7%) cases with PI-ENKTCL were identified out of 2017 archived ENKTCL cases, with a median age of 39 years and a male to female ratio of 2.1:1. The most common symptom was abdominal pain (90.9%), accompanied frequently with fever and less commonly with intestinal perforation or B symptoms. Small intestine (50.9%) was the most common site to be involved. 47.3% and 36.4% cases presented with stage I and II diseases, respectively. Histologically, most cases displayed characteristic morphologic changes of ENKTCL. Cytoplasmic CD3, TIA-1 and CD56 expression was found in 100%, 94.5% and 89.1% of cases, respectively. In situ hybridization detection for EBV demonstrated positive results in all cases. Monoclonal TCR gene rearrangement was found in 52.9% of tested cases. Chemotherapy with a DICE or L-asparaginase/peg-asparginase-containing regimen was most often employed. Both advanced tumor stage and B symptoms were independent inferior prognostic factors (p = 0.001 and p = 0.010). Noticeably, 6 cases demonstrated a CD4-positive phenotype. These cases featured a relatively older median age (58 years), predominance of small/medium-sized neoplastic cells, a higher rate of TCR rearrangement and slightly favorable outcome. CONCLUSION: We reported by far the largest series of PI-ENKTCL, and demonstrated its heterogeneity, aggressive clinical behavior and unsatisfying response to the current therapeutic strategies. Those CD4-positive cases might represent a unique subtype of PI-ENKTCL or distinct entity. Further investigations are required for the better understanding and management of this unusual disease.

N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro.

Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR's expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801's influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA's direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

The Octyl Ester of Ginsenoside Rh2 Induces Lysosomal Membrane Permeabilization via Bax Translocation.

Ginsenoside Rh2 is a potential pharmacologically active metabolite of ginseng. Previously, we have reported that an octyl ester derivative of ginsenoside Rh2 (Rh2-O), has been confirmed to possess higher bioavailability and anticancer effect than Rh2 in vitro. In order to better assess the possibility that Rh2-O could be used as an anticancer compound, the underlying mechanism was investigated in this study. The present results revealed that lysosomal destabilization was involved in the early stage of cell apoptosis in HepG2 cells induced by Rh2-O. Rh2-O could induce an early lysosomal membrane permeabilization with the release of lysosomal protease cathepsins to the cytosol in HepG2 cells. The Cat B inhibitor (leu) and Cat D inhibitor (pepA) inhibited Rh2-O-induced HepG2 apoptosis as well as tBid production and Δφm depolarization, indicating that lysosomal permeabilization occurred upstream of mitochondrial dysfunction. In addition, Rh2-O induced a significant increase in the protein levels of DRAM1 and Bax (p < 0.05) in lysosomes of HepG2 cells. Knockdown of Bax partially inhibited Rh2-O-induced Cat D release from lysosomes. Thus it was concluded that Rh2-O induced apoptosis of HepG2 cells through activation of the lysosomal-mitochondrial apoptotic pathway involving the translocation of Bax to the lysosome.

[Quantitatively evaluating the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment].

OBJECTIVE: To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. METHODS: To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining. RESULTS: Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5±1.5) ml·(100 ml)(-1)·min(-1,) 0.14±0.04, (45.7±16.5)/HPF, respectively, and those in the control group were (13.4±1.6) ml·(100 ml)(-1)·min(-1) , 0.14±0.05, (48.0±7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9±7.3), (32.2±6.9), (18.5±2.4) and (13.8±1.8) ml·(100 ml)(-1)·min(-1,) respectively, and those in the control group were (10.5±0.6), (9.6±0.8), (5.7±1.2) and (1.9±1.0) ml·(100 ml)(-1)·min(-1,) respectively. The values of VMI of the treatment group were 1.17±0.22, 3.25±0.23, 2.94±0.31 and 1.07±0.18, respectively, and those in the control group were 0.12±0.03, 0.13±0.03, 0.15±0.03, and 0.13±0.03, respectively. The values of MVD of the treatment group were (38.0±6.3), (24.3±5.4), (15.2±3.4) and (13.5±4.7)/HPF, respectively, and those in the control group were (44.8±5.9), (48.0±12.8), (41.8±5.7) and (45.7±20.3)/HPF, respectively. In treated mice, BF and VMI were significantly higher than those in the control group (all P<0.01). BF and VMI increased from day2, and reached the peak at day4 (P<0.01), then decreased at day6, however the value of BF at day6 was still higher than that in the baseline (P<0.01) and decreased to the baseline level at day10; while the value of VMI was still higher than that in the baseline at day10. And on the forth, sixth, tenth days of treatment, in treated mice, the values of MVD were significantly lower than those in the control group and the baseline level before treatment (all P<0.01). In control mice, BF decreased (all P<0.01) with the time, while MVD and VMI had no changes. CONCLUSIONS: The tumor perfusion and vessel maturity are transiently increased in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. VPCT is helpful to quantify the evolution of the tumor perfusion and then evaluate the functional changes of tumor vessel maturity.

Esterification of Ginsenoside Rh2 Enhanced Its Cellular Uptake and Antitumor Activity in Human HepG2 Cells.

Our previous research had indicated that the octyl ester derivative of ginsenoside Rh2 (Rh2-O) might have a higher bioavailability than Rh2 in the Caco-2 cell line. The aim of this study was to investigate the cellular uptake and antitumor effects of Rh2-O in human HepG2 cells as well as its underlying mechanism compared with Rh2. Results showed that Rh2-O exhibited a higher cellular uptake (63.24%) than Rh2 (36.76%) when incubated with HepG2 cells for 24 h. Rh2-O possessed a dose- and time-dependent inhibitory effect against the proliferation of HepG2 cells. The IC50 value of Rh2-O for inhibition of HepG2 cell proliferation was 20.15 µM, which was roughly half the value of Rh2. Rh2-O induced apoptosis of HepG2 cells through a mitochondrial-mediated intrinsic pathway. In addition, the accumulation of ROS was detected in Rh2-O-treated HepG2 cells, which participated in the apoptosis of HepG2 cells. Conclusively, the findings above all suggested that Rh2-O as well as Rh2 inducing HepG2 cells apoptosis might involve similar mechanisms; however, Rh2-O had better antitumor activities than Rh2, probably due to its higher cellular uptake.

A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic features.

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing melanotic features. Microscopically, the histologic features mimic clear cell renal cell carcinoma. However, the dark-brown pigments were identified and could be demonstrated as melanins. Immunohistochemically, the tumor cells were widely positive for CD10, human melanoma black 45, and TFE3 but negative for cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor, smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3 fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease with 50 months of follow-up. The prognosis of this type of tumor requires more cases because of limited number of cases and follow-up period. Xp11.2 RCC with PSF-TFE3 inevitably requires differentiation from other kidney neoplasms. Immunohistochemical and molecular genetic analyses are essential for accurate diagnosis.

Intraneobladder Hem-o-Lok Migration with Stone Formation after Orthotopic Neobladder Cystectomy.

Introduction. Laparoscopic and robot-assisted laparoscopic surgery are widely performed in urology field, so Hem-o-Lok clips are thus extensively used in the laparoscopic procedures. We describe the first case of Hem-o-Lok clip which migrated into the neobladder with calculus formation 26 months after laparoscopic orthotopic neobladder cystectomy, which causes symptoms of gross hematuria and frequent urination. Case Presentation. A 57-year-old man with T2a muscle invasive bladder cancer underwent laparoscopic orthotopic sigmoid neobladder reconstruction after cystectomy which was complicated by intestinal anastomosis leak and peritoneal abscess requiring transverse colostomy and drainage 15 days postoperatively. Twenty-six months after cystectomy, he complained of gross hematuria and frequent urination. Computerized tomography and plain pelvic X-ray revealed a stone measuring approximately 2.8 cm in diameter in the neobladder. During cystoscopy, a closed whitish Hem-o-Lok clip was seen in the center of the calculi. No anastomotic leak or neoplasm was found during cystoscopy. Conclusion. Hem-o-Lok clip migration into the bladder after laparoscopic orthotopic neobladder cystectomy is a rare complication; the first reported case in the literature. To prevent Hem-o-Lok clip migration, it is recommended to avoid extensive use of Hem-o-Lok clip close to anastomosis site, and any loose Hem-o-Lok clip should be retrieved before closure.