Untargeted metabolomics profiling in a mouse model of lung cancer treated with thermal ablation.

Thermal ablation is widely used in the treatment of lung cancer and is beneficial for the overall survival of patients in clinic. However, there is barely a priority in which ablation system should be chosen under different periods of tumor progression in lung cancer. The present study investigated different modes of thermal ablation systems in mice with transplanted Lewis lung carcinoma tumors and their various biological effects in local regions using untargeted metabolomics. The results showed that thermal ablation could significantly suppress tumor growth and the differentially expressed metabolites of tumors after ablation relative to untreated tumors concentrated on organic compounds, organic acids and derivatives, nucleosides, nucleotides, and lipids. The upregulated metabolites indicated an inflammatory reaction in the ablation groups at an early stage after ablation. Steroid hormone and tryptophan metabolism, which are associated with immune responses, were modulated after both cryoablation and hyperthermal ablation. Characteristically, the results also indicated that cryoablation suppressed glucose oxidation and carbohydrate metabolism of tumor, while hyperthermal ablation suppressed lipid metabolism of tumor. In conclusion, thermal ablation could inhibit tumor growth under either freezing or heating modes with characteristic different biological effects on tumors.

Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.

BACKGROUND/AIM: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. MATERIALS AND METHODS: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNA-sequencing was performed on tumors in the high-dose XHW group and the control group. RESULTS: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'-monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. CONCLUSION: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.

Efficacy and safety of complementary and alternative medicine therapy for gastroparesis: A protocol for systematic review and meta-analysis.

BACKGROUND: Gastroparesis affects the quality of life of many patients, but there is no effective treatment. Now, complementary and alternative medicine originated from China is gradually accepted by the world because of its unique treatment principles and relatively safe treatment methods. However, at present, there is still a lack of more definitive clinical application evidence for the treatment of gastroparesis with complementary and alternative medicine to confirm the safety and efficacy of complementary and alternative medicine in the treatment of gastroparesis caused by various causes. More comprehensive and stronger evidence-based medicine evidence is needed. METHODS: We will retrieve literatures using Medline, Embase, the Cochrane Library database, Web of science, CNKI, VIP, CBM, and WanFang. We will look for RCTs or CCTs on the use of complementary and alternative medicine in the treatment of gastroparesis, and extract relevant data into the excel sheet. The whole retrieval and data extraction process were carried out by 2 researchers independently. Then we will use meta-analysis to make statistical analysis of all the results and make a systematic review of all the included literatures. RESULTS: All results and safety data were analyzed for a comprehensive evaluation and/or descriptive analysis of the efficacy and safety of complementary and alternative therapies for gastroparesis. CONCLUSION: This study will provide more comprehensive clinical evidence for the treatment of gastroparesis with complementary and alternative therapies. REGISTRATION: The research has been registered and approved on the INPLASY.COM website. The registration number is INPLASY2020100033.

Cryoablation for advanced non-small cell lung cancer: a protocol for a systematic review.

INTRODUCTION: National Comprehensive Cancer Network has recommended cryoablation to replace the resection in the treatment of medically operable non-small cell lung cancer (NSCLC). Cryoablation also has been used for the advanced NSCLC in randomised controlled trials. However, they have not been systematically reviewed. Here, we provide a protocol to evaluate the effectiveness and safety of cryoablation in the treatment of advanced NSCLC. METHODS AND ANALYSES: We will search PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database without language restrictions from inception until 1 February 2020. Trial registers (International Clinical Trials Registry platform, the US National Institutes of Health Ongoing Trials Register and the ISRCTN registry) and reference lists of retrieved articles will also be searched. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes and assess the methodological quality by the Cochrane risk of bias tool. The strength of evidences will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. Review Manager V.5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous. The primary outcomes will be objective response rate and overall survival. The secondary outcomes will be adverse effects, health-related quality of life, changes of immune indicators and surrogate outcomes (disease control rate, progression-free survival and survival rate). ETHICS AND DISSEMINATION: Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research. PROSPERO REGISTRATION NUMBER: CRD42019138660.

Chinese herbal medicine si-miao-san decoction for acute gouty arthritis: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The prevalence of gout is increasing worldwide, and the symptoms of acute arthritis appearing in gout patients seriously affect the quality of life. The pain and functional limitation caused by acute gouty arthritis (AGA) bring great pain to patients. At present, mainstream drugs have problems such as poor efficacy and side effects. Traditional Chinese medicine has extensive clinical experience in the prevention and treatment of gout, and it also shows clear advantages in the treatment of AGA. Clinical studies have confirmed that si-miao-san decoction (SMSD), a traditional Chinese medicine decoction, can improve the clinical symptoms and signs of AGA patients. Therefore, we will conduct a systematic review to clarify the effectiveness and safety of SMSD for AGA. METHODS: We will search different database from the built-in to October 2020. The electronic database includes PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and CBM. At the same time, we will also search for clinical registration tests and gray literatures. This study only screened clinical randomized controlled trials (RCT) for SMSD for AGA. The 2 researchers independently conducted literature selection, data extraction, and quality assessment. Dichotomous data are represented by relative risk (RR), continuous data are represented by mean difference (MD) or standard mean deviation (SMD), and the final data are fixed effect model (FEM) or random effect model (REM), depending on whether it exists heterogeneity. The main outcomes are clinical efficacy, including pain score, joint function, and degree of swelling. The secondary outcomes include: blood uric acid (BUA), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Finally, a meta-analysis was conducted through Review Manager software version 5.3. RESULTS: This study will conduct a comprehensive analysis based on the currently released Si-Miao-San data for the treatment of AGA and provide high-quality evidence of clinical efficacy and safety. CONCLUSION: This systematic review aims to provide new options for SMSD treatment of AGA in terms of its efficacy and safety. ETHICS AND DISSEMINATION: The review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines, or peer-reviewed journals. INPLASY REGISTRATION NUMBER: INPLASY202040163.

Application of Zizao Yangrong Granules for Treating Targeted Drugs-Related Skin Xerosis: A Randomized Double-Blinded Controlled Study.

Background: Dermatologic toxicities are the most common side effects associated with the targeted drugs epidermal growth factor receptor inhibitors (EGFRIs), in which xerosis commonly complicated by pruritus severely disturbs the quality of life. The study has observed the curative effect of Zizao Yangrong granules (ZYG) from Chishui Xuanzhu in the treatment of EGFRIs-related xerosis and pruritus, as well as evaluating the safety of the prescription. Methods: Patients (n = 68) who had xerosis after using EGFRIs were enrolled and then randomly divided into the treatment group and control group, respectively, receiving ZYG and placebo granules combined with vitamin E ointment. The intervention lasted 4 weeks. Changes in xerosis and pruritus were observed, and blood routine examination as well as liver and kidney function are observed as safety indexes. The water content of skin and qualify of life were observed. Results: A total of 66 out of 68 patients finished the study with 34 patients in each group. The effective rates of xerosis among the treatment group and control group were 84.8% and 69.7% after 2 weeks' treatment (P < .05), while they were 84.8% and 75.8% after 4 weeks' treatment (P < .05). The patients in the experimental group had better quality of life than that in the control group (P = .045). Conclusion: ZYG can effectively improve the skin dryness associated with EGFRIs, and significantly improve the quality of life of patients with good safety; however, larger randomized controlled trials are needed to verify these findings.

Treatment of severe rash caused by crizotinib with both traditional Chinese medicine and Western medicine: Two case reports and literature review.

RATIONALE: Lung adenocarcinoma is the most common pathologic pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment. Crizotinib is generally well tolerated while its most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac and endocrine abnormalities. Rash caused by crizotinib is rarely seen, and there are few case reports of severe rash caused by crizotinib. PATIENT CONCERNS AND DIAGNOSES: Here we report cases of an 81-year-old man and a 66-year-old woman with ALK-rearranged advanced lung adenocarcinoma. When patients came to our department, they both had crizotinib-induced severe rash. INTERVENTIONS: Crizotinib was initiated as the 1st-line treatment without other therapies. We treated severe rash with traditional Chinese medicine (TCM) therapy called Zhiyang Pingfu liquid along with Western medicine. Zhiyang Pingfu liquid consists of Scutellaria baicalensis 20 g, Portulaca oleracea 30 g, Cortex Dictamni 30 g, Sophora flavescens 30 g, and other substances. Western medicine includes Minocycline hydrochloride tablets and Aprepitant capsules. OUTCOMES: Both patients achieved a partial response when treated with crizotinib, and suffered from severe rash. With Zhiyang Pingfu liquid and Western medicine, their rash gradually disappeared with no sign of cancer progression. Also the male patient did not relieve after taking only antibiotics (standard therapy) and anti-allergic medicine. LESSONS: Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution. This is the 1st case in which TCM and Western medicine are used to successfully treat crizotinib-induced severe rash. The mechanism of crizotinib-induced rash deserves further attention in future research.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

New polyoxygenated cyclohexene and polyoxygenated seco-cyclohexene from Uvaria boniana.

A new polyoxygenated cyclohexene bonianol A (1) and another new polyoxygenated seco-cyclohexene bonianol B (2) were isolated from the leaves of Uvaria boniana, and their structures were established on the basis of spectroscopic methods including IR, HR-ESI-MS, 1D, and 2D NMR.

[Identification of the prior regions for agricultural and rural pollution control in Changshu].

The characteristics such as wide area, dispersion and randomness of agricultural and rural pollution make it difficult to seize the key to pollution control in rural areas. On the scale of township, using inventory analysis, accounting for emissions and emission intensity of the chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP) in Changshu, Jiangsu Province, which exists in a total of 4 classes and 6 kinds of agricultural and rural sources such as farmland cultivation (chemical fertilizer application and crop straw abandoned), animal breeding, aquaculture, rural life (domestic sewage and human waste, solid waste), using cluster analysis, identify the prior regions and the prior pollution sources for agricultural and rural pollution control by the sensitivity evaluation, and make agricultural and rural pollution control and management measures more focused. It shows that: in 2007, COD, TN and TP emissions of agricultural and rural pollution sources were 5496.07, 4161.03, and 647.54 t x a(-1), and the emission intensity of COD, TN and TP was 48.84, 36.98, and 5.75 kg x hm(-2). The main pollution source of COD was rural life and aquaculture, and the contribution rate was more than 75%; the main pollution source of TN and TP was agricultural cultivation and aquaculture, and the contribution rate was more than 80%. The sensitivity evaluation identified that the town of Guli and Shajiabang were the prior regions for agricultural and rural pollution control in Changshu; farmland cultivation and aquaculture were the prior pollution sources in the two areas.