Search

Yuying Shi,1– 3,* Mengyuan Dai,1– 3,* Yaxing Zhang,1– 3 Yuwen Qi,1– 3 Zhen Li,1– 3 Hongbing Cai1– 3 1Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, Hubei, People’s Republic of China; 3Hubei Cancer Clinical Study Center, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbing CaiZhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaTel +86-1-339-716-8990Email chb21051@163.comIntroduction: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer characterized by highly aggressive and poor prognosis. However, it is unclear what factors are associated with OCCC recurrence and death. The study aimed to evaluate whether residual tumor diameter after primary debulking surgery, or other clinicopathological features play roles in predicting survival outcome in stage II–IV OCCC patients.Material and Methods: We present a retrospective study of OCCC patients with stage II–IV in our department from 2010 to 2015. Kaplan–Meier method was used to draw a survival curve. Survival analysis was performed using Log-rank test for univariate analysis and COX proportional risk regression model for multivariate analysis.Results: In this cohort of 78 patients who underwent primary debulking surgery, 47 patients had disease recurrence and 32 cases died. On univariate analysis, FIGO stage, residual tumor diameter and ascites were significant predictors of 3-year PFS (P values< 0.05) and OS (P values< 0.05). On multivariate analysis, the residual tumor diameter was an independent prognostic factor for 3-year PFS and OS (P values< 0.05). The outcomes of patients in residual-free group were significantly better than those in the residual tumor diameter 0– 1cm and > 1cm group (PFS: P=0.000, OS: P=0.001), but there was no significant difference in prognosis between 0– 1cm and > 1cm group (P values > 0.05). Greater residual tumor diameter predicted progression on cox analysis in patients with stage III, but not for patients with stage IV.Conclusion: Residual tumor diameter is prognostic after surgery for OCCC. Achieving no residual disease will significantly improve the prognosis inadvanced OCCC patients.Keywords: ovarian clear cell carcinoma, residual tumor diameter, progression

Background Chinese herbal medicine is widely used in combination with usual care for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China. Chinese patent medicine Shufeng Jiedu (SFJD) capsules is widely used for respiratory infectious diseases. This review aims to evaluate effectiveness and safety of SFJD for AECOPD. Methods A systematic review of randomised controlled trials (RCTs) in patients with AECOPD, who received SFJD as a single intervention or as add-on treatment to usual care. PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science and four Chinese databases were searched from inception to April 2019. Two authors screened trials, extracted data, and assessed risk of bias, independently. Meta-analysis was performed using RevMan 5.3 software. We performed subgroup analyses and sensitivity analyses according to the predefined protocol. Quality of evidence was assessed using GRADE. Results Thirteen RCTs (1036 patients, with 936 inpatients) were included, all compared SFJD in combination with usual care (including antibiotics) to usual care alone. The mean age of participants ranged from 52 to 67 years, with approximately 60% male. Due to lack of blinding and other factors, all trials were of high risk of bias. SFJD was associated with a significant reduction in treatment failure, from 20.1 to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62), and duration of hospital stay (2 trials; 79 patients; mean difference − 4.32 days, 95% CI − 5.89 to − 2.75 days). No significant difference in adverse events was found between SFJD and control groups. Conclusion Low certainty evidence suggests SFJD may bring additional benefit in reducing treatment failure, shorten hospital stay, and improving symptoms. Further large, high quality RCTs are needed to confirm its benefit and safety. Trial registration PROSPERO CRD42019133682.

Background Exposure to particulate matters (PMs) can lead to an acute exacerbation of allergic airway diseases, increasing the severity of symptoms and mortality. However, little is known about the underlying molecular mechanism. This study aimed to investigate the effects of PMs on acute exacerbation of allergic airway inflammation and seek potential therapeutic targets. Methods Non-allergic control and ovalbumin (OVA)-allergic wide-type (WT) and Toll-like receptor 2 knockout (Tlr2-/-) mice were exposed to 100 μg of PM (diameter 5.85 μm) or saline by the oropharyngeal instillation. The responses were examined three days after exposure. In the RAW264.7 macrophage cell line, Tlr2 was knocked down by small-interfering RNA or the NF-κB inhibitor JSH-23 was used, and then the cells were stimulated with PMs for 12 h before comparison of the inflammatory responses. Results PM exposure led to increased inflammatory cell recruitment and airway intensity of PAS + staining in OVA-allergic WT mice, accompanied with an accumulation of inflammatory cells and elevated inflammatory cytokines, such as IL-6 and IL-18, in the bronchoalveolar lavage fluid (BALF). Furthermore, the protein levels of TLR2 and the NLRP3 inflammasome were elevated concomitantly with the airway inflammation post-OVA/PMs challenge. Tlr2 deficiency effectively inhibited the airway inflammation, including pulmonary inflammatory cell recruitment, mucus secretion, serum OVA-specific immunoglobulin E (IgE), and BALF inflammatory cytokine production. Additionally, the P-induced NLRP3 activation in the RAW 264.7 cell line was diminished by the knockdown of Tlr2 or JSH-23 treatment in vitro. Conclusion Our results indicated that PMs exacerbate the allergic airway inflammation mediated by the TLR2/ NF-κB/NLRP3 signaling pathway. Inhibition of NF-κB seems to be a possible treatment.

The recent coronavirus disease (COVID‐19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and has been spreading rapidly throughout the continents. The insights in how this viral disease affects general population is thus urgently needed. Diabetes mellitus is one of the leading threats for morbidity and mortality globally. Infection of coronavirus in diabetic patients may trigger acute hyperglycemia due to increased secretion of hyperglycemic hormones, extensive application of glucocorticoids to patients with severe symptoms and the potential pathogenicity of coronavirus in pancreas expressing angiotensin‐converting enzyme 2 (ACE2) This article is protected by copyright. All rights reserved.

Patients with lung cancer are presumed to be at high risk from COVID-19 infection due to underlying malignancy. A total of 31 COVID-19 patients with pre-diagnosed lung cancer and 186 age and sex matched COVID-19 patients without cancer in 6 hospitals in Wuhan, China were identified in our study. There was a significantly higher level of IL-6 in lung cancer group showed by multifactorial analysis. The restricted mean survival time in 10, 20, and 53 days in COVID-19 patients with lung cancer were ealier than non-cancer COVID-19 patients in the same observation time (all P values < 0.05). Our results indicated that pre-diagnosed lung cancer was associated with higher morbidity and mortality in COVID-19 patients.

Background The management of critically ill patients with coronavirus disease 2019 (COVID‐19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID‐19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID‐19 receiving CP treatments by total immunoglobulin G (IgG) titer collection. Methods Three patients with COVID‐19 in this study were laboratory confirmed to be positive for SARS‐CoV‐2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200‐225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed. Results No therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion. Conclusions We recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID‐19 pneumonia.

Supplemental Material, Revised_Supplement_Appendix for Patients With Lung Cancer Have High Susceptibility of COVID-19: A Retrospective Study in Wuhan, China by Meng-Yuan Dai, Zhen Chen, Yan Leng, Meng Wu, Yu Liu, Fuxiang Zhou, Chen Ming, Ningyi Shao, Miao Liu and Hongbing Cai in Cancer Control

Additional file 1: Table 1. Herbal compositions of Shufeng Jiedu capsule. Table 2. Definitions of treatment failure in 11 trials. Table 3. Subgroup analyses and sensitivity analyses for treatment failure with Shufeng Jiedu for AECOPD patients. Figure 1. Impact of Shufeng Jiedu capsule on treatment failure in AECOPD patients stratified by mode of administration of antibiotics. Figure 2. Impact of Shufeng Jiedu on treatment failure in AECOPD patients stratified by complications. Figure 3. Impact of Shufeng Jiedu on treatment failure in AECOPD patients stratified by clear or unclear randomization concealment. Figure 4. Impact of Shufeng Jiedu on treatment failure in AECOPD patients stratified by reported loss to follow up or not reported. Figure 5. Impact of Shufeng Jiedu on treatment failure in AECOPD patients used worst plausible assumptions of patients lost to follow up or not used. Figure 6. Impact of Shufeng Jiedu on duration of hospital stay (days) in AECOPD patients. Table 4. Certainty in the estimates rated according to the GRADE.

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. Significance: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747

Chemical investigation of

Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction‑inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC.

The dietary compound phenethyl isothiocyanate (PEITC), an important tumoricidal component found in cruciferous vegetables, exhibits strong anticancer and chemopreventive effects in a variety of tumors. However, its role in human laryngeal cancer is unclear. The aim of the present study was to investigate whether PEITC exhibits anticancer properties in human laryngeal carcinoma Hep-2 cells in vitro and to identify the potential molecular mechanisms. The results showed that treatment of Hep-2 cells with PEITC significantly inhibited cell proliferation in a dose- and time-dependent manner, promoted apoptosis with concurrent G2/M cell cycle arrest and inhibited cell invasion in a dose-dependent manner. These effects were accompanied by significant alterations in the expression levels of key proteins associated with pro-survival signaling pathways, including PI3K, Akt, ERK, NF-κB, Bcl, Bax, cyclin B, CDK4 and CDK6. Importantly, these effects were not reflected in 16HBE normal human bronchial epithelial cells, suggesting a safe range of treatment concentrations between 0 and 10 µM PEITC. In summary, PEITC exhibited significant anticancer effects against human laryngeal cancer cells in vitro with low toxicological impact on normal bronchial epithelial cells. This was achieved through dysregulation of key proteins involved in the occurrence and development of tumors, thereby offering a valuable contribution to future strategies for the treatment and screening of patients with laryngocarcinoma.

The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 are needed. We performed a multi-center study including 105 cancer patients and 536 age-matched non-cancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematological cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Non-metastatic cancer patients experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, while patients with only radiotherapy did not demonstrate significant differences in severe events when compared to patients without cancer. These findings indicate that cancer patients appear more vulnerable to SARS-COV-2 outbreak. Since this is the first large cohort study on this topic, our report will provide the much-needed information that will benefit global cancer patients. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. Citation Format: Meng-Yuan Dai, Dian-bo Liu, Miao Liu, Fu-Xiang Zhou, Gui-Ling Li, Zhen Chen, Zhi-An Zhang, Hua-You Md, Meng Wu, Qi-Chao Zheng, Yong Xiong, Hui-Hua Xiong, Chun Wang, Chang-Chun Chen, Fei Xiong, Yan Zhang, Ya-Qin Peng, Si-Ping Ge, Bo Zhen, Ting-Ting Yu, Ling Wang, Hua Wang, Yu Liu, Ye-Shan Chen, Jun-Hua Mei, Xiao-Jia Gao, Zhu-Yan Li, Li-Juan Gan, Can He, Zhen Li, Yu-Ying Shi, Yu-Wen Qi, Jing Yang, Daniel G. Tenen, Li Chai, Lorelei Ann Mucci, Mauricio Santillana, Hongbing Cai. Patients with cancer appear more vulnerable to SARS-COV-2: A multi-center study during the COVID-19 outbreak [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT406.

Chemical investigation of Lansium domesticum has led to the isolation of two undescribed compounds, namely 17(20)E-dyscusin B (1) and 17(20)Z-dyscusin B (2), as well as three known ones (3 – 5). Structural elucidation was accomplished by the analysis of NMR, MS and IR data. Compounds 1 and 2 were a pair of Δ17(20) geometric isomers of pregnane steroids and showed the significant nitric oxide (NO) inhibitory activities.

Galectin-1 (Gal-1) has immunomodulatory activities in various allergic inflammatory disorders, but its potential anti-inflammatory properties on allergic airway diseases have not been confirmed. We explored the pharmacological effects of Gal-1 on the progression of allergic airway inflammation and investigated the underlying mechanism. Female C57BL/6 mice were sensitized on day 0 and challenged with ovalbumin (OVA) on days 14-17 to establish an allergic airway inflammation model. In the challenge phase, a subset of mice was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). We found that rGal-1 inhibited pulmonary inflammatory cell recruitment, mucus secretion, bronchoalveolar lavage fluid (BALF) inflammatory cell infiltration, and cytokine production. The treatment also suppressed the infiltration of eosinophils into the allergic lung as indicated by decreased expression levels of eotaxin and eosinophil peroxidase (EPX). However, only the expression levels of IL-25, neither IL-33 nor TSLP, were significantly decreased in the lung by rGal-1 treatment. These immunomodulatory effects in the allergic lung were correlated with the activation of extracellular signal-regulated kinase (ERK) signaling pathway and downregulation of endogenous Gal-1. In addition, rGal-1 reduced the plasma concentrations of anti-OVA immunoglobulin E (IgE) and IL-17. Our findings suggest that rGal-1 is an effective therapy for allergic airway inflammation in a murine model and may be a potential pharmacological target for allergic airway inflammatory diseases.

Aberrant microRNA (miRNA) expression has been linked to cancer development. In this study, we aimed to investigate whether the anti‑cancer effect of miRNA‑299‑3p on laryngeal cancer Hep‑2 cells is mediated through targeting human telomerase reverse transcriptase (hTERT). The expression of miR‑299‑3p in laryngeal cancer Hep‑2 cells and human osteosarcoma U2OS cells was quantified by stem‑loop‑mediated reverse transcription quantitative polymerase chain reaction. miR‑299‑3p mimic was transfected into Hep‑2 cells to induce overexpression of miR‑299‑3p. A CCK‑8 assay was performed to identify the effects of miR‑299‑3p overexpression on the proliferation of Hep‑2 cells. Western blot analysis was carried out to determine the expression of hTERT protein. A significant decrease was noted in the expression of miR‑299‑3p in Hep‑2 cells compared with that of U2OS cells (P0.05). Overexpression of miR‑299‑3p resulted in a notable inhibition of cellular proliferation (P0.05), as well as downregulation of hTERT mRNA and protein in Hep‑2 cells (P0.05). The expression of miR‑299‑3p is downregulated in human laryngeal cancer Hep‑2 cells. Overexpression of miR‑299‑3p inhibits Hep‑2 cell growth by targeting the 3'‑untranslated region of hTERT mRNA.

Meng-Yuan Dai,1 Jin-Ping Qiao,2 Yuan-Hong Xu,2 Guang-He Fei1 1Pulmonary Department, 2Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic ofChina Purpose: To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD). Patients and methods: We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups. The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture. LOS and CAT as well as demographic information were recorded. Results: Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both. Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus. Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae. The longest LOS and the highest CAT score were detected in coinfection group. CAT score was positively correlated with LOS. Conclusion: Respiratory infection is a common causative agent of exacerbations in COPD. Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS. CAT score may be a predictor of longer LOS in AECOPD. Keywords: COPD, acute exacerbation, respiratory infectious, phenotypes, LOS, CAT

Notch signaling plays a key role in a wide variety of human tumors; it can be an oncogene or a tumor-suppressor gene depending on the tissue context. The functions of Notch1 in laryngeal squamous cell carcinoma (LSCC) are largely unknown. We investigated the role of Notch1 in LSCC cell growth, apoptosis and metastasis. We analyzed Notch1 expression in clinical LSCC samples using quantum dot immunohistochemistry (QD-IHC) and conventional IHC. Human laryngeal carcinoma HEp-2 cells were transfected with Notch1-specific short hairpin RNA (shRNA), and cell proliferation, apoptosis, and migration and invasion were evaluated using the cell counting assay, flow cytometry and wound healing and Transwell assays, respectively; western blotting was used to validate the expression of Notch1 target genes. Compared with normal tissues, Notch1 was upregulated in LSCC tissues; compared with LSCC tissues without metastasis, Notch1 upregulation was enhanced in LSCC tissues with metastasis (P

Notch signaling is important during the development of a variety of human tumors. Depending on the context, Notch signaling can be either oncogenic or anti-proliferative, and therefore, its effects in cancer are unpredictable. The aim of the present study was to identify the importance of Notch 2 in the cell growth and metastasis of laryngeal squamous cell carcinoma (LSCC). The current study performed quantum dots-based immunofluorescence histochemistry to determine expression of Notch 2 in 72 LSCC samples without lymph node metastasis, 23 LSCC samples with lymph node metastasis and 31 samples from vocal cord polyps. It was observed that Notch 2 was upregulated in LSCC tissue compared with normal vocal cord polyps. This upregulation was further enhanced in LSCC tissues with lymph node metastasis compared with LSCC tissues without lymph node metastasis. Following knockdown of NOTCH2 expression in LSCC cells, the in vitro tumorigenicity of Hep-2 cells was inhibited, with growth, migration, invasion and proliferation reduced, and apoptosis induced. Additionally, following downregulation of Notch 2 protein expression, the protein expression levels of phosphor-mitogen-activated protein kinase 1 (p-ERK), v-myc avian myelocytomatosis viral oncogene homolog and B-cell CLL/lymphoma 2 (Bcl2) were also downregulated, whereas, Bcl2-associated X protein expression was upregulated. There were no changes detected in the protein expression levels of total-ERK, phospho-v-akt murine thymoma viral oncogene homolog 1 (p-Akt) and total-Akt. The results of the present study suggest that Notch 2 is important for the cell growth, anti-apoptosis and metastasis of LSCC. Therefore, Notch 2 inhibitors may have therapeutic potential for the treatment of patients with LSCC via the inhibition of cancer cell growth and metastasis.